Development of a Porcine Model of Pulmonary Ischemia-Reperfusion Injury Relevant to Post-Esophagectomy Acute...

Background: Acute respiratory distress syndrome (ARDS) occurs in 20-40% of patients following esophagectomy and is associated with substantial postoperative morbidity and mortality. A major contributor to postoperative ARDS is pulmonary ischemia-reperfusion injury (IRI); however, the role of IRI in ARDS following esophagectomy is not adequately addressed in current experimental models. In this study, we established a large animal model of pulmonary IRI that reproduces key physiological, inflammatory, and histopathological features of pulmonary ischemia-reperfusion-induced acute lung injury relevant to postoperative ARDS after esophagectomy. Methods: Sequential pulmonary ischemia-reperfusion injury was induced in ten anesthetized Landrace pigs using unilateral hilar inflow occlusion. Right lung ischemia was achieved by clamping the hilar inflow for three hours, followed by reperfusion. Subsequently, the left lung underwent two hours of ischemia. Hemodynamic, respiratory, and inflammatory parameters were continuously monitored throughout the experiment. Blood samples were collected to assess leukocyte counts and circulating inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. Lung tissue samples were obtained for histopathological evaluation. Results: ARDS-like lung injury was successfully induced in all animals, with PaO₂/FiO₂ ratios falling below 200 mmHg during the predefined reperfusion observation period. Lung compliance decreased by approximately 50% after ischemia and further declined following reperfusion. Progressive leukocyte elevation and elevated tumor necrosis factor-α and interleukin-6 levels were observed, indicating a systemic inflammatory response. Hallmark features of ARDS were histologically confirmed, including intra-alveolar hemorrhage, interstitial and perivascular edema, and neutrophil infiltration. Conclusions: This porcine model reproduces key physiological, inflammatory, and histopathological features consistent with pulmonary ischemia-reperfusion-induced ARDS-like lung injury. Although it does not reproduce the complete clinical syndrome of post-esophagectomy ARDS, it provides a clinically relevant translational platform for investigating pulmonary ischemia-reperfusion injury and evaluating potential preventive and therapeutic strategies.