Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model

Abstract

Background: Ischemia-reperfusion injury involves free radical generation and polymorphonuclear neutrophil chemotaxis. Trimetazidine is an anti-ischemic drug that restores the ability of the ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. We evaluated the effect of trimetazidine against ischemia-reperfusion injury after lung transplantation. Methods: Rat single lung transplantation was performed in 3 experimental groups (n = 5): (1) the immediate transplantation group was defined as animals undergoing transplantation immediately after harvest without treatment; (2) the ischemic control group was defined as animals undergoing transplantation after 18 hours of cold (4°C) ischemia without treatment; and (3) the trimetazidine-treated group was defined as animals undergoing transplantation after 18 hours of cold (4°C) ischemia and donor and recipient treatment with 5 mg/kg intravenous trimetazidine 10 minutes before harvest and reperfusion, respectively. All donor lungs were flushed with low-potassium dextran-glucose solution. After 2 hours of reperfusion, oxygenation was measured, and lung tissue was frozen and assessed for adenosine triphosphate content, myeloperoxidase activity, and thiobarbituric acid–reactive substances. Peak airway pressure was recorded throughout the reperfusion period. Results: The trimetazidine group showed significantly higher levels of adenosine triphosphate content (1.73 ± 0.8 pmol vs 0.72 ± 0.2 pmol [ischemic control], P =.008), better oxygenation (238.82 ± 113.9 mm Hg vs 89.39 ± 14.7 mm Hg [ischemic control], P =.008), and reduced lipid peroxidation (1.28 ± 0.1 nmol/g vs 2.09 ± 0.4 nmol/g [ischemic control], P =.008). Adenosine triphosphate levels of the trimetazidine group were comparable with those of the immediate transplantation group (1.73 ± 0.8 pmol vs 1.89 ± 0.5 pmol, respectively; P =.31). Peak airway pressure and myeloperoxidase activity were comparable among groups. Conclusion: Donor and recipient treatment with trimetazidine provided a significant protection of the energy status, better oxygenation, and reduced lipid peroxidation in this experimental model. Our data suggest that trimetazidine may be an important adjunct to prolong ischemic time safely and to decrease lung ischemia-reperfusion injury.