Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model.
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 degrees C) ischemia without treatment; and (3) the trimetazidine-treated group was defined as animals undergoing transplantation after 18 hours of cold (4 degrees 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.


CONCLUSIONS
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.
Inci
I
I
Division of Thoracic Surgery, University Hospital, Switzerland.
Dutly
A
A
Rousson
V
V
Boehler
A
A
Weder
W
W
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism; D015227:Lipid Peroxidation; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D016040:Lung Transplantation; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D009195:Peroxidase; D014292:Trimetazidine