Experimental Swine lung autotransplant model to study lung ischemia-reperfusion injury

Abstract

Introduction: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical and experimental models of cold ischemia. However, relatively few studies examine the detailed biochemical changes occurring during normothermic (warm) IR. The objective of this work was to establish an experimental lung autotransplant model to be carried out on pigs in order to study the early stages of normothermic lung IR. ANIMALS Y METHODS: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy, ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughout the procedure, several parameters were measured in order to identify hemodynamic, gasometric and biochemical changes. Non-parametric statistical analyses were used to compare differences between periods.

Results: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatory cytokines and chemokines (TNF-α, IL-1β y MCP-1), neutrophil activation, inducible nitric oxide synthase activity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitric oxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same held true throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activity was also shown.

Conclusions: An experimental model of normothermic lung IR injury is presented and detailed changes in hemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parameters may be clinically useful in future investigations testing new therapies to prevent normothermic IR induced lung injury.