Original Article
Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs
Ensayo piloto de conservación pulmonar hipotérmica prolongada para analizar la lesión de isquemia-reperfusión en cerdos
Amaia Ojangurena,b,
, Maite Santamaríac, Lucía Milla-Colladoa, Carlos Frailea, Sonia Gatius-Calderód, Sara Puye, Alba Boldóe, Susana Gómez-Ollesf,g, Meritxell Boada-Pérezf,g, Cristina Esquinasg, Berta Sáez-Giménezf, Iñigo Ojangurenf,g, Miriam Barrechegurenf,g, Jorge Juan Olsina-Kisslerc
Corresponding author
a Thoracic Surgery Department, Arnau de Vilanova University Hospital, Lleida, Spain
b Thoracic Surgery Department, Lausanne University Hospital, Lausanne, Switzerland
c General Surgery Department, Arnau de Vilanova University Hospital, Lleida, Spain
d Pathology Department, Arnau de Vilanova University Hospital, Lleida, Spain
e Centre de Reserca Experimental Biomèdica Aplicada (CREBA), IRBLleida, Lleida, Spain
f Pneumology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
g CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
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Lleida, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Thoracic Surgery Department, Lausanne University Hospital, Lausanne, Switzerland" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "General Surgery Department, Arnau de Vilanova University Hospital, Lleida, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pathology Department, Arnau de Vilanova University Hospital, Lleida, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centre de Reserca Experimental Biomèdica Aplicada (CREBA), IRBLleida, Lleida, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Pneumology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ensayo piloto de conservación pulmonar hipotérmica prolongada para analizar la lesión de isquemia-reperfusión en cerdos" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0035" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 713 "Ancho" => 1333 "Tamanyo" => 73916 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Lung transplantation (LT) is the mainstay for treatment for patients with end-stage lung disease. Unfortunately, the shortage of suitable donors for transplantation remains a limiting factor and a challenge.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> Indeed, in most multiorgan-donors lungs are too deteriorated for donation and only 20–25% are acceptable for LT.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">2</span></a> Hence, it is critical to develop new strategies to increase the pool of organ donors. In this context, several alternatives have been investigated in recent years, including the use of so-called extended criteria donor lungs, the use of donors after cardiocirculatory death, and the implementation of ex vivo lung perfusion.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Extending the accepted graft ischemia-time may increase the utility of donor lungs by enlarging the time frame to perform long distance lung procurements. Cold preservation has been the classic procedure to reduce lung injury while the organ is transported from donor to recipient. During lung procurement, lungs are flushed with a low potassium dextran solution, inflated with oxygen and stored at 4<span class="elsevierStyleHsp" style=""></span>°C. The objective of hypothermic organ preservation is to decrease the cellular metabolism of the graft and thus, reduce the cell death ratio. However, ischemic insult leads to the generation of reactive oxygen species that result in cell injury.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a> In this respect, it is worth noting that the limit of cold ischemia time (CIT) is poorly defined. In clinical LT, 8<span class="elsevierStyleHsp" style=""></span>h is the generally accepted upper limit for CIT. Accordingly, extending the arbitrarily established ischemia time is a matter of debate because of the perceived increased rate of ischemia-reperfusion (IR) injury that could lead to primary graft disfunction (PGD).<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In the early post-operative period, PGD is the leading cause of morbidity and mortality, with up to 20% of recipients developing severe PGD. An important feature of PGD is the early development of inflammation as the result of the activation of innate immune mechanisms. These mechanisms involve the activation of pro-inflammatory transcription factors that induce the expression of inflammatory mediators, primarily inflammatory cytokines and chemokines, which promote the recruitment of activated leukocytes and subsequent inflammatory cytotoxic consequences.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7–9</span></a> The mechanisms responsible for the triggering of innate immune response and acute inflammation in IR injury have not been elucidated so far. In this respect, several clinical series have demonstrated that the perceived detrimental effect of extended graft ischemia time on PGD might not be well founded.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">10–12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In view of the limited evidence in the clinical setting, the objective of the present study was to analyze the impact of extended CIT on IR injury following LT in a swine experimental model by means of determination of histologic injury, inflammatory profile and cell death in the lung graft.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was an experimental, randomized pilot trial of parallel groups and a final blind analysis using a swine model of LT developed for the purpose of the study. Animals received humane care during experiments in compliance with the “The Guide for the Care and Use of Laboratory Animals” and were housed and handled in accordance with European law (Directive 2010/63/EU). The study was evaluated and approved by hospital and competent authority's Ethics Committee on Animal Research (no. 10325). Sixteen female commercial hybrid pigs weighing 30–35<span class="elsevierStyleHsp" style=""></span>kg were used (8 as donors and 8 as receptors).</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0030" class="elsevierStylePara elsevierViewall">Donor animals (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8) were submitted to organ procurement under general anesthesia. The lungs were separated into two groups, the 6h-CIT group (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) and the 12h-CIT group (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) and were respectively subjected to 6<span class="elsevierStyleHsp" style=""></span>h and 12<span class="elsevierStyleHsp" style=""></span>h of ischemic aerobic hypothermic static preservation. At the end of the preservation, the left lung was transplanted into a recipient animal and re-perfused for 4<span class="elsevierStyleHsp" style=""></span>h (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Donor procedure</span><p id="par0035" class="elsevierStylePara elsevierViewall">Pigs were sedated with ketamine (8<span class="elsevierStyleHsp" style=""></span>mg/kg im), midazolam (0.6<span class="elsevierStyleHsp" style=""></span>mg/kg im), and xylazine 20% (2.2<span class="elsevierStyleHsp" style=""></span>mg/kg im). Induction was carried out in the operating room with inhaled sevoflurane 4% with 1<span class="elsevierStyleHsp" style=""></span>L/min oxygen via face mask. Cefazolin (20<span class="elsevierStyleHsp" style=""></span>mg/kg iv) and methylprednisolone (500<span class="elsevierStyleHsp" style=""></span>mg iv) were administered after induction. Pigs were cannulated with an endotracheal tube. Maintenance agents consisted of propofol (5–8<span class="elsevierStyleHsp" style=""></span>mg/kg/h iv) and remifentanil (2–20<span class="elsevierStyleHsp" style=""></span>mcg/kg/h iv) infusions. Animals were ventilated with a pressure-controlled ventilator at 15<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O, a tidal volume of 6–8<span class="elsevierStyleHsp" style=""></span>ml/kg, positive end-expiratory pressure (PEEP) of 5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O, with a respiratory rate of 15<span class="elsevierStyleHsp" style=""></span>breaths/min, and a FiO<span class="elsevierStyleInf">2</span> of 0.5. Median sternotomy was performed and the superior and inferior vena cava were encircled with silk ties. A bolus of heparin 10.000<span class="elsevierStyleHsp" style=""></span>U/ml was injected intravenously. A 21 French cannula was inserted into the main pulmonary artery (PA). A bolus of 500mcg prostaglandin E<span class="elsevierStyleInf">1</span> was injected in the main PA. The superior and inferior cava were ligated, a clamp was placed across the aorta and the left atrial appendage was transected. The PA was flushed with Perfadex Plus (60<span class="elsevierStyleHsp" style=""></span>ml/kg) solution at 4<span class="elsevierStyleHsp" style=""></span>°C. The trachea was stapled with the lungs inflated with a sustained airway pressure of 15cmH<span class="elsevierStyleInf">2</span>O. A retrograde flush through the left atrium with 15<span class="elsevierStyleHsp" style=""></span>ml/kg of Perfadex Plus solution was performed. The heart-lung bloc was placed in a plastic bag containing 500<span class="elsevierStyleHsp" style=""></span>ml of Perfadex Plus at 4<span class="elsevierStyleHsp" style=""></span>°C.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Lung transplant procedure</span><p id="par0040" class="elsevierStylePara elsevierViewall">The recipient pigs were sedated and anesthesized in the same way as the donors. A left thoracotomy was performed through the fourth intercostal space. The left azygous vein was ligated and the inferior pulmonary ligament divided. A vascular clamp was placed proximally on the left main PA which was divided distally. The left pulmonary veins were ligated and divided. Then, the bronchus was divided. Bronchial anastomosis was performed with a running 4/0 Prolene suture, PA anastomosis with a continuous 5/0 Prolene suture and then atrial anastomosis with a running 5/0 Prolene suture. After re-inflation of the transplanted lung to a pressure of 20–25<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O, the PA clamp was removed gradually and the lung was de-aired through the left atrial anastomosis. The lungs were then ventilated with 60% oxygen, 5<span class="elsevierStyleHsp" style=""></span>cm H<span class="elsevierStyleInf">2</span>O PEEP and the respiratory rate was adjusted to keep the <span class="elsevierStyleItalic">p</span>CO<span class="elsevierStyleInf">2</span> between 35 and 40<span class="elsevierStyleHsp" style=""></span>mmHg.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Allograft tissue sample collection</span><p id="par0045" class="elsevierStylePara elsevierViewall">Lung tissue biopsies were collected from the left lower lobe at the following time points: (a) CIT<span class="elsevierStyleInf">0</span>: at the beginning of the CIT, (b) CIT<span class="elsevierStyleInf">1</span>: at the end of the CIT; (c) Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>: 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion of the left LT; (d) Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>: 4<span class="elsevierStyleHsp" style=""></span>h after reperfusion of the left LT. Half of the biopsy was stained with hematoxylin–eosin, whereas the other half was flash frozen in liquid nitrogen and stored at −80<span class="elsevierStyleHsp" style=""></span>°C.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Histologic assessment of microscopic lung injury and lung edema</span><p id="par0050" class="elsevierStylePara elsevierViewall">A pulmonary pathologist calculated the histopathologic grading of acute lung injury according to the following parameters: interstitial edema, intra-alveolar edema, hemorrhage, cell infiltration and hyaline membrane formation.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> The severity of the findings was graded on a scale from 0 (absent) to 3 (severe). The lung injury score developed on this basis is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The wet-to-dry weight ratio was used to evaluate lung edema by measuring the degree of water in the lung.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Lung tissue homogenates preparation and ELISA for cytokines</span><p id="par0060" class="elsevierStylePara elsevierViewall">The inflammatory response was analyzed in lung tissue samples stored at −80<span class="elsevierStyleHsp" style=""></span>°C. Lung tissue cytokines IFN-γ, IL-1β, IL6, IL10 and TNF-α were evaluated with the Cytokine & Chemokine 9-Plex Porcine ProcartaPlex™ Panel 1 (ThermoFisher Scientific, Bender MedSystems GmbH, Vienna, Austria). Cytokine concentrations were calculated using the ProcartaPlex Analyst software.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Apoptotic cell death pathway, caspase-3 in tissue</span><p id="par0065" class="elsevierStylePara elsevierViewall">The detection of activated caspase 3 provided a sensitive means of detecting apoptotic cells. Endogenous peroxidase was blocked before staining the sections. Antibodies against cleaved caspase-3 (Asp175) (1:100, Cell Signaling Technology, United States) were used. Immunoexpression was graded semiquantitatively by considering the percentage of stained cells. A percentage score was obtained from each sample applying the following formula: (stained cells in the slide/total cells in the slide)<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Statistical methods</span><p id="par0070" class="elsevierStylePara elsevierViewall">Absolute frequencies and percentages were used to describe the qualitative variables. Quantitative variables were described using the mean, standard deviation (SD), median and quartiles. The Kolmogorov–Smirnov test was used to assess the normality of distributions. The variables, weight (kg), <span class="elsevierStyleItalic">P</span>O<span class="elsevierStyleInf">2</span> (mmHg) and warm ischemia time (WIT) (min), were compared between study groups (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h) in donor and recipient animals using the <span class="elsevierStyleItalic">U</span> Mann–Whitney test. Differences between study groups in cytokine levels at different timepoints were analyzed using the Mann–Whitney test. Cytokine patterns in each group during the experiment were also analyzed using the Friedman test. For all the tests, <span class="elsevierStyleItalic">P</span>-values of <0.05 were considered statistically significant. The statistical package R Studio (2.5) was used for the statistical analyses.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Baseline characteristics</span><p id="par0075" class="elsevierStylePara elsevierViewall">No statistically significant differences were found between the pigs subjected to 6<span class="elsevierStyleHsp" style=""></span>h or 12<span class="elsevierStyleHsp" style=""></span>h CIT in the operative variables of, donor/recipient body weight, donor/recipient partial pressure of arterial oxygen (<span class="elsevierStyleItalic">P</span>O<span class="elsevierStyleInf">2</span>) before thoracotomy and WIT (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Recipient’ monitoring parameters throughout the reperfusion period in the 6h-CIT and 12h-CIT groups are collected in the Appendix 1 (supplementary material).</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Histologic lung injury and pulmonary edema</span><p id="par0085" class="elsevierStylePara elsevierViewall">In the histologic assessment, lungs subjected to 6<span class="elsevierStyleHsp" style=""></span>h or 12<span class="elsevierStyleHsp" style=""></span>h static cold storage presented no statistically significant differences in the lung injury score at any given time, as follows: median lung injury score at (i) CIT<span class="elsevierStyleInf">0</span>, 1 vs. 1 (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.317) for the 6h-CIT and 12h-CIT group, respectively; (ii) CIT<span class="elsevierStyleInf">1</span>, 1.5 vs. 1.5 (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.752); (iii) Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 2.5 vs. 2 (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.659) and; (iv) Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 2.5 vs. 3.5 (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.304). In all cases, the tissue obtained 4<span class="elsevierStyleHsp" style=""></span>h after lung reperfusion showed greater tissue injury (score rank 1–5) than the corresponding sample at the end of the cold ischemia (score rank 1–3). However, in both situations the score corresponded to a mild pulmonary lesion (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The histological analysis revealed a case of pneumonia in one lung corresponding to the 6h-CIT group. In this particular graft, mild (corresponding to timepoint CIT<span class="elsevierStyleInf">0</span>) to severe (corresponding to CIT<span class="elsevierStyleInf">1</span>, Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> and Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>) cellular inflammation was identified in hematoxylin & eosin (H&E) staining. This fact was not noticed during the macroscopic inspection when performing the pulmonary procurement.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">In the lung edema assessment, no significant differences were found in the wet/dry lung weight ratio between groups at any given time (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Lung injury scale parameters throughout the experiment in 6h-CIT and 12h-CIT groups are collected in Appendix 2 (supplementary material).</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Inflammatory response</span><p id="par0100" class="elsevierStylePara elsevierViewall">Throughout the experiment no significant differences were found between the groups corresponding to 6<span class="elsevierStyleHsp" style=""></span>h and 12<span class="elsevierStyleHsp" style=""></span>h of hypothermic static preservation in the ELISA analysis for the following inflammatory cytokines: IFN-γ, IL-1β, IL6, IL10 and TNF-α (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). There was a slight amount of IFN-γ detected during reperfusion, but its peak remained close to baseline values (median 0.02<span class="elsevierStyleHsp" style=""></span>pg/mg). Among the proinflammatory cytokines, IL-1β and IL6 showed an upward trend during the reperfusion period. No significant differences in the regulatory cytokine IL10 were observed. TNF-α was barely detected during CIT (at CIT<span class="elsevierStyleInf">1</span>, the median TNF-α quantity measured in pg/mg was 0.09 vs. 0.32 for 6h-CIT and 12h-CIT, respectively: <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.773), but was clearly detected within 30<span class="elsevierStyleHsp" style=""></span>min of reperfusion (at Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, the median TNF-α quantity was 0.17 vs. 0.56 for 6h-CIT and 12h-CIT, respectively: <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.386) and then returned to baseline values.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Apoptotic cell death – immunohistochemistry quantification of caspase-3</span><p id="par0105" class="elsevierStylePara elsevierViewall">The semiquantitative analysis of caspase-3 immunostaining showed an increasing trend throughout the experiment. The median percentage of caspase-3 positive cells increased from 7.5% vs. 10% at timepoint CIT<span class="elsevierStyleInf">0</span> (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.647), to 15% vs. 25% at timepoint Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>mim</span> (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.659) for the 6h-CIT and 12h-CIT groups, respectively. Peak expression of caspase-3 was observed in samples corresponding to 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion of the transplanted lung. The increase was similar in the 6h-CIT and 12h-CIT groups (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). The highest percentage of caspase-3 positive cells (40%) was found at timepoint Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, corresponding to the 6h-CIT graft with pneumonia. Representative images of caspase-3 positive cell staining are shown in <a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a> in chronological order along the timepoints of the experiment.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">In this pilot swine model of LT after extended CIT, the performance of donor lungs that underwent 12<span class="elsevierStyleHsp" style=""></span>h CIT was found to be as good as that of lungs that underwent 6<span class="elsevierStyleHsp" style=""></span>h CIT. No differences were found in terms of decisive characteristics of acute lung injury<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">14,15</span></a> such as microscopic lung injury, lung edema, inflammation or apoptosis.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The maximum safe preservation time for human LT remains undefined. However, there is a reluctance to extend the conventionally accepted <8<span class="elsevierStyleHsp" style=""></span>h of cold ischemia.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a> Thabut et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a> analyzed data from 752 patients who underwent LT in seven French transplantation centers during a 12-year period. Graft ischemic time was associated with early PGD and with long-term survival in patients undergoing single or double LT, but not in patients undergoing heart-lung transplantation. More recently, a retrospective study based on United Network of Organ Sharing (UNOS) database evaluated the effect of prolonged total graft ischemia times (<span class="elsevierStyleUnderline">></span>6<span class="elsevierStyleHsp" style=""></span>h) on long-term survival and the development of PGD.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> Interestingly, prolonged graft ischemia was not associated with an increase in 1 and 5-year mortality and was also not a negative predictor of PGF.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Bearing in mind that reproducibility in animal research and translation from bench to bedside is still a challenge,<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> our large animal model study design emulated the clinical setting where lungs recovered for transplantation require a period of aerobic cold ischemic preservation to be transported back to the transplant center.</p><p id="par0125" class="elsevierStylePara elsevierViewall">IR injury is inevitable in solid organ transplantation.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a> However, the lung has to be considered differently because it contains oxygen in the alveoli which, helps to maintain aerobic metabolism and prevents hypoxia during ischemic preservation.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">19–21</span></a> In addition, ischemia is characterized by the absence of blood flow into the lung, which can cause oxidant injury despite the presence of oxygen. Thus, it can occur during the storage period.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">21,22</span></a> Our results with regards to microscopic lung injury deteriorated to a similar degree in both the 6h-CIT and 12h-CIT groups after reperfusion. Activation of the innate immune system induces the expression of inflammatory mediators which promote the recruitment of activated leukocytes that have subsequent inflammatory cytotoxic consequences.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">18,23,24</span></a> We assessed the development of graft inflammation through the evaluation of key proinflammatory cytokines. The exposure of lung cells to 6 and 12<span class="elsevierStyleHsp" style=""></span>h of CIT followed by 4<span class="elsevierStyleHsp" style=""></span>h of reperfusion resulted in enhanced proinflammatory cytokines such as TNF-α, IL-1β and IL-6. Interestingly, we observed that TNF-α protein was expressed early and then returned to baseline production at 4<span class="elsevierStyleHsp" style=""></span>h of reperfusion. This early appearance of TNF-α supports the implication that it regulates the expression of other proinflammatory cytokines and affects neutrophil recruitment as early as 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion. We did not observe a significant IFN-γ response due to the short reperfusion period. It has been demonstrated that recipient T-cell activation occurs during the late phase of IR injury together with IFN-γ release in a lung transplant setting.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a> Likewise, levels of IL-10, the only anti-inflammatory cytokine, remained barely detectable during the reperfusion period.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Unlike necrosis, apoptosis does not occur during ischemia, though it does increase during reperfusion.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">26</span></a> The induction of apoptosis can occur through the intrinsic or extrinsic pathway. The first is dependent on mitochondria and is activated by reactive oxygen species. The second is dependent on inflammatory molecules, such as TNF-α. In LT, it has been observed that apoptosis peaks rapidly after reperfusion corresponding to up to 30% cells of lung graft.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a> In our study, caspase-3 activity was used as a hallmark indicator of apoptosis in LT.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> Although caspase-3 did increase during the reperfusion period, the increase was only slight and did not differ between the study groups. Peak expression of caspase-3 was observed in samples corresponding to 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion. Interestingly, this timepoint coincides with peak expression of TNF-α. In addition, our data suggest that the presence of apoptosis was not related with lung function in terms of edema development. Similar results have been reported in other studies in an experimental setting.<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">29,30</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">This study has several limitations in the context of large animal experimental models. First, given its nature as a pilot study, the trial was designed as an initial test to analyze CIT in early ischemia-reperfusion injury. For this reason, it was conducted with a small number of subjects and, consequently, its statistical power to detect differences was compromised. Second, the reperfusion period was 4<span class="elsevierStyleHsp" style=""></span>h, far below the 72 h-range covered by the clinical definition of PGD. However, we believe that this does not introduce significant bias as a large number of published works are limited to a 2–4-h reperfusion period.<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">31–33</span></a> Because of the complexity of the swine LT model, the literature regarding 3 days survival after LT is scarce.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">34,35</span></a> Thirdly, one of the animals in the 6h-CIT group presented a pneumonia that was not detected macroscopically during lung procurement. Interestingly, this animal had the highest microscopic injury score and apoptotic cell death percentage. In fact, infection is a well-known risk factor for the development of PGD.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a> The design of our study mirrors clinical practice where lungs recovered for transplantation require a period of cold ischemic preservation. However, bearing in mind the complex setting of the lung transplant procedure, a clinical trial with prolonged CITs would not be feasible for ethical reasons. It is therefore difficult to translate measures taken in an experimental context into clinical practice. In any case, because humans share more immune-system-related genes and proteins with pigs than rodents or other animals, the swine model is the most widely used large animal model in the context of lung transplantation. Although our study represents a proof of concept in pigs, its preliminary outcomes warrant further testing using a larger sample size with a longer-term survival model.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Nonetheless, there are also a number of noteworthy strengths in our study. To begin with, we believe that our work provides relevant information about the extension of the arbitrarily stablished ischemia time. Geographically distant organ procurement may be facilitated by increasing the viable time frame.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Our study additionally provides evidence to support a CIT of above 12<span class="elsevierStyleHsp" style=""></span>h to obtain a model of moderate lung damage in the experimental setting. Using a histological lung injury score, as well as inflammation and apoptosis analyses, our study shows that 12<span class="elsevierStyleHsp" style=""></span>h of CIT leads to mild damage. Thus, lungs that are completely healthy, or only mildly damaged, may not reflect the potential improvement provided by any tested treatment. Accordingly, the most recent experimental studies involving pig lung damage models apply CITs ranging from 18 to 24<span class="elsevierStyleHsp" style=""></span>h.<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">37–39</span></a> Finally, as our work precisely describes the technique of LT in pigs, recording not only the anesthetic and surgical protocols but also the technical information for sample processing, it consequently enables the reproducibility of these complex procedures.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion, we have demonstrated in a swine model that post-transplant lung allograft injury was equivalent in specimens that underwent 6<span class="elsevierStyleHsp" style=""></span>h or 12<span class="elsevierStyleHsp" style=""></span>h CIT. No statistically significant differences were found in lung injury markers between the two groups. The extent of lung injury measured using a microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild. The implications that may arise from this study should be taken with caution due to its experimental character. Outcomes from this study warrant further testing using a bigger sample size and longer-term survival model to investigate the role of CIT in PGD.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Contributions</span><p id="par0155" class="elsevierStylePara elsevierViewall">(I) Conception and design: Ojanguren A; (II) Administrative support: Ojanguren A, Olsina-Kissler JJ; Provision of study materials: Ojanguren A, Milla L, Fraile-Olivero C, Puy S; Olsina-Kissler JJ; (IV) Collection and assembly of data: Ojanguren A, Milla L, Fraile C, Puy S, Santamaria M.; (V) Data analysis and interpretation: Ojanguren A, Gatius S, Gómez-Olles S, Boada-Pérez M, Esquinas C, Santamaria M; (VI): Manuscript writing: All authors; (VII); Final approval of manuscript: All authors.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Disclosure</span><p id="par0160" class="elsevierStylePara elsevierViewall">M.B. has received speaker fees from Grifols, Menarini, CLS Behring, GSK and Boehringer Ingelheim, and consulting fees from GSK, Novartis, Boehringer Ingelheim and GebroPharma, outside the submitted work.</p><p id="par0165" class="elsevierStylePara elsevierViewall">I.O. has received travel grants, consulting fees, speaker fees, or research grants from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, MSD, GlaxoSmithKline, Menarini, Mundipharma, Novartis, and Teva, outside the submitted work.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict of interests</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interests related to this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1542042" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1542041" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1394994" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1542043" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1394993" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Donor procedure" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Lung transplant procedure" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Allograft tissue sample collection" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Histologic assessment of microscopic lung injury and lung edema" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Lung tissue homogenates preparation and ELISA for cytokines" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Apoptotic cell death pathway, caspase-3 in tissue" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Statistical methods" ] ] ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Baseline characteristics" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Histologic lung injury and pulmonary edema" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Inflammatory response" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Apoptotic cell death – immunohistochemistry quantification of caspase-3" ] ] ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Contributions" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Disclosure" ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflict of interests" ] 12 => array:2 [ "identificador" => "xack543145" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-12-29" "fechaAceptado" => "2021-03-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1394994" "palabras" => array:5 [ 0 => "Lung transplant" 1 => "Swine model" 2 => "Ischemia-reperfusion injury" 3 => "Cold ischemia" 4 => "Lung preservation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1394993" "palabras" => array:5 [ 0 => "Trasplante de pulmón" 1 => "Modelo porcino" 2 => "Lesión de isquemia-reperfusión" 3 => "Isquemia fría" 4 => "Conservación pulmonar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Background</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8) were submitted to organ procurement. Lungs were subjected to 6<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) or 12<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4<span class="elsevierStyleHsp" style=""></span>h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion, and (iv) 4<span class="elsevierStyleHsp" style=""></span>h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6<span class="elsevierStyleHsp" style=""></span>h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30<span class="elsevierStyleHsp" style=""></span>min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30<span class="elsevierStyleHsp" style=""></span>min after reperfusion.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">We observed that 6 and 12<span class="elsevierStyleHsp" style=""></span>h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En el trasplante de pulmón (TP), la duración del tiempo de isquemia es controvertida, ya que se estableció de forma arbitraria. Sería útil explorar el impacto del tiempo de isquemia fría (TIF) prolongado sobre la lesión de isquemia-reperfusión en un modelo experimental.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Ensayo piloto experimental aleatorizado de grupos paralelos y análisis ciego final utilizando un modelo de TP en cerdos. Se extrajeron los órganos de los animales donantes (<span class="elsevierStyleItalic">n<span class="elsevierStyleHsp" style=""></span>=</span><span class="elsevierStyleHsp" style=""></span>8). Los pulmones se conservaron durante 6 horas (<span class="elsevierStyleItalic">n<span class="elsevierStyleHsp" style=""></span>=</span><span class="elsevierStyleHsp" style=""></span>4) o 12 horas (<span class="elsevierStyleItalic">n<span class="elsevierStyleHsp" style=""></span>=</span><span class="elsevierStyleHsp" style=""></span>4) en hipotermia aeróbica. El pulmón izquierdo se trasplantó y reperfundió durante 4 horas. Se obtuvieron biopsias de pulmón (i) al comienzo del TIF, (ii) al final del TIF, (iii) 30 minutos después de la reperfusión y (iv) 4 horas después de la reperfusión. Los injertos de pulmón se evaluaron histológicamente mediante la puntuación de daño histológico pulmonar y la relación de peso húmedo y peso seco. La respuesta inflamatoria se valoró mediante la determinación de citoquinas inflamatorias. Se determinó la actividad de caspasa-3 como marcador de apoptosis.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">No observamos diferencias en la puntuación de daño histológico pulmonar o en la relación de peso húmedo y peso seco en un momento dado entre los pulmones sometidos a 6 h-TIF o 12 h-TIF. Las IL-1β e IL-6 mostraron una tendencia ascendente durante la reperfusión en ambos grupos. El TNF-α alcanzó su punto máximo dentro de los 30 minutos posteriores a la reperfusión. Apenas se detectó IFN-γ. La inmunoexpresión de caspasa-3 se clasificó semicuantitativamente por el porcentaje de células teñidas. Se observó un 20% de células apoptóticas 30 minutos después de la reperfusión.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Observamos que 6 y 12 horas de TIF fueron equivalentes en términos de daño histológico pulmonar, perfil inflamatorio y apoptosis en un modelo de TP en cerdos. La extensión de la lesión pulmonar, medida por la puntuación de daño histológico pulmonar, las citoquinas proinflamatorias y la determinación de caspasa-3 fue leve.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0195" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0105" ] ] ] ] "multimedia" => array:11 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1608 "Ancho" => 3005 "Tamanyo" => 214732 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Study design. This study was comprised of 2 groups (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4 each). Swine donor lungs were preserved at 4<span class="elsevierStyleHsp" style=""></span>°C for 12<span class="elsevierStyleHsp" style=""></span>h in the 12h-CIT group, and for 6<span class="elsevierStyleHsp" style=""></span>h in the 6h-CIT group, respectively. The left lungs were transplanted and reperfused for 4<span class="elsevierStyleHsp" style=""></span>h. Lung tissue samples were collected at different timepoints as follows: (i) CIT<span class="elsevierStyleInf">0</span>: at the beginning of the CIT, (ii) CIT<span class="elsevierStyleInf">1</span>: at the end of the CIT; (iii) Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>: 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; (iv) Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>: 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left LT. CIT: cold ischemia time; LT: lung transplant.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2923 "Ancho" => 2923 "Tamanyo" => 313506 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Lung injury score. Score 0: no pulmonary injury; score 1–5: mild pulmonary injury; score 6–10: moderate pulmonary injury and score 11–15: severe pulmonary injury. Q1: first quartile; Q3, third quartile; SD, standard deviation. CIT indicates cold ischemia time; CIT<span class="elsevierStyleInf">0</span>, beginning of the CIT; CIT<span class="elsevierStyleInf">1</span>, end of the CIT; Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left lung tranplant. <span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">P</span>-values obtained from the Mann–Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h). <span class="elsevierStyleSup">b</span><span class="elsevierStyleItalic">P</span>-values obtained from the Friedman test (CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3007 "Ancho" => 3007 "Tamanyo" => 368277 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Wet-to-dry ratio. Q1: first quartile; Q3, third quartile; SD, standard deviation. CIT: cold ischemia time; CIT<span class="elsevierStyleInf">0</span>, beginning of the CIT; CIT<span class="elsevierStyleInf">1</span>, end of the CIT; Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left lung tranplant. <span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">P</span>-values obtained from the Mann–Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h). <span class="elsevierStyleSup">b</span><span class="elsevierStyleItalic">P</span>-values obtained from the Friedman test (CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 4329 "Ancho" => 2889 "Tamanyo" => 360128 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The lines show the expression of proinflammatory cytokines in lung tissue throughout the experiment. CIT: cold ischemia time; CIT<span class="elsevierStyleInf">0</span>, beginning of the CIT; CIT<span class="elsevierStyleInf">1</span>, end of the CIT; LT, lung transplant; Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left LT. <span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 obtained from the Mann–Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h). <span class="elsevierStyleSup">b</span><span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 obtained from the Friedman test (CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>). <span class="elsevierStyleSup">c</span><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>; <span class="elsevierStyleSup">d</span><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>; <span class="elsevierStyleSup">e</span><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 3007 "Ancho" => 3007 "Tamanyo" => 348526 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Caspase-3 semiquantitative analysis. Q1: first quartile; Q3, third quartile; SD, standard deviation. CIT: cold ischemia time; CIT<span class="elsevierStyleInf">0</span>, beginning of the CIT; CIT<span class="elsevierStyleInf">1</span>, end of the CIT; Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left lung transplant. <span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">P</span>-values obtained from the Mann-Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h). <span class="elsevierStyleSup">b</span><span class="elsevierStyleItalic">P</span>-values obtained from the Friedman test (CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>).</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 2073 "Ancho" => 2508 "Tamanyo" => 1047323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Apoptotic cell death is assessed by immunohistochemistry quantification of caspase-3. Caspase-3 positive cells are stained in brown. Representative images (a)–(d). According to the semiquantitative analysis, the percentage of stained cells in lung tissue as follows: (a) 5% corresponding to timepoint CIT<span class="elsevierStyleInf">0</span>; (b) 5% corresponding to timepoint CIT<span class="elsevierStyleInf">1</span>; (c) 20% corresponding to timepoint Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>; and (d) 15% corresponding to timepoint Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h.</span></p>" ] ] 6 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lung injury scale</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interstitial edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alveolar edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemorrhage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cell infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyaline membrane formation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2647760.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Lung injury score</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Points \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe damage \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2647758.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Histopathological assessment by lung injury score.</p>" ] ] 7 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">WIT: warm ischemia time. Q1: first quartile; Q3, third quartile; SD, standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Statistic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">6<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Donor</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Weight (kg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31.31 (3.21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.38 (3.54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.25 (3.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.306 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.25 (28.5; 34.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (28; 32.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.25 (29.75; 34.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">P</span>O<span class="elsevierStyleInf">2</span> (mmHg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">488.38 (92.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">443 (82.31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">533.75 (87.65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.149 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">506 (412; 567) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">450.5 (380; 506) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">567 (485; 582.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Recipient</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Weight (kg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.25 (3.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.88 (3.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.63 (3.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.663 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.5 (32; 37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.25 (31.5; 36.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.75 (32.25; 37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">P</span>O<span class="elsevierStyleInf">2</span> (mmHg)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">460.88 (107.28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">471.75 (60.26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">450 (151.36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">467 (420; 526) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">467 (420; 523.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">469.5 (337; 563) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>WIT (min)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91.88 (11.32) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.25 (6.29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.5 (15.89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.564 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93 (85; 100.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">91 (85; 95.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98 (81.5; 105.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2647759.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">P</span>-values obtained from the Mann–Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Donor and recipient baseline characteristics.</p>" ] ] 8 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">CIT: cold ischemia time; CIT<span class="elsevierStyleInf">0</span>, beginning of the CIT; CIT<span class="elsevierStyleInf">1</span>, end of the CIT; LT, lung transplant; Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>, 30<span class="elsevierStyleHsp" style=""></span>min after the reperfusion of the left LT; Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>, 4<span class="elsevierStyleHsp" style=""></span>h after the reperfusion of the left LT.</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span><span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 obtained from the Mann–Whitney test (6<span class="elsevierStyleHsp" style=""></span>h vs 12<span class="elsevierStyleHsp" style=""></span>h).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Timepoint \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Statistic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">6<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleSup">a</span> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IFN-γ pg/mg</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">0</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.04 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.767 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">1</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.248 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.885 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.885 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.02; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 (0.01; 0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.282 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.627 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-1β pg/mg</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">0</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.13 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.18 (0.13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.191 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0.07; 0.15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.15 (0.08; 0.28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0.07; 0.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">1</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.18 (0.27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.29 (0.37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.149 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0.07; 0.12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 (0.07; 0.51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 (0.07; 0.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.92 (1.17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.39 (1.54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.564 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.34 (0.08; 1.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12 (0.13; 2.65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.29 (0.08; 0.82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.18 (0.96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.43 (1.13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.93 (0.85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.564 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12 (0.43; 1.66) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12 (0.61; 2.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.97 (0.2; 1.66) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.105 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL6<span class="elsevierStyleHsp" style=""></span>pg/mg</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">0</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.39 (0.35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.52 (0.49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.767 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0.25; 0.29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 (0.25; 0.79) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0.25; 0.26) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">1</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.27 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 (0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.27 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.885 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0.25; 0.28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 (0.25; 0.28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 (0.25; 0.29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.05 (0.77) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.22 (1.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.88 (0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.773 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.84 (0.6; 1.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.84 (0.62; 1.82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.91 (0.51; 1.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.19 (0.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.08 (0.41) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.386 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.24 (0.8; 1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.08 (0.8; 1.36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.58 (0.74; 1.85) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.050<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL10<span class="elsevierStyleHsp" style=""></span>pg/mg</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">0</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 (0.62) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.91 (0.87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.767 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.44; 0.51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.5 (0.44; 1.38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.44; 0.45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">1</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 (0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.47 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.468 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.44; 0.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 (0.44; 0.49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.44; 0.45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.71 (0.49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 (0.66) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6 (0.29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.554 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 (0.44; 0.83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.53 (0.45; 1.22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 (0.44; 0.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61 (0.59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.47 (0.06) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.74 (0.87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.885 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.44; 0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 (0.44; 0.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44 (0.24; 1.23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.282 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.807 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNFα pg/mg</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">0</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.89 (1.44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.19 (2.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.58 (0.67) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.773 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 (0.03; 1.11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 (0.03; 2.35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.43 (0.05; 1.11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CIT<span class="elsevierStyleInf">1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.4 (0.53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.42 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.38 (0.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.773 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 (0.03; 0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 (0.03; 0.81) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.32 (0.06; 0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.05 (1.78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.42 (2.59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.69 (0.56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.386 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 (0.16; 1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17 (0.09; 2.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 (0.28; 1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.2 (0.28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 (0.27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.23 (0.33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.191 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Median (Q1; Q3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.04 (0.03; 0.34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03 (0.03; 0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 (0.04; 0.42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">P</span>-value<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.082 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.165 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2647757.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010"><span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 obtained from the Friedman test (CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>).</p>" ] 1 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span>.</p>" ] 2 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison CIT<span class="elsevierStyleInf">1</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>.</p> <p class="elsevierStyleNotepara" id="npar0025"><span class="elsevierStyleSup">e</span><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for pairwise comparison Rp<span class="elsevierStyleInf">30<span class="elsevierStyleHsp" style=""></span>min</span> vs Rp<span class="elsevierStyleInf">4<span class="elsevierStyleHsp" style=""></span>h</span>.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Inflammatory cytokines throughout the experiment in 6h-CIT and 12h-CIT groups.</p>" ] ] 9 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 155253 ] ] 10 => array:5 [ "identificador" => "fig0035" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 713 "Ancho" => 1333 "Tamanyo" => 73916 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "OPTN/SRTR 2017 Annual Data Report: Lung" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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