Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation

Background: Ischemia-reperfusion injury remains an important obstacle to su ccessful lung transplantation. Trimetazidine is an anti-ischemic drug that restores the ability of ischemic cells to produce energy and reduces the ge neration of oxygen-derived free radicals. The aim of this study was to asse ss the protective effect of trimetazidine after prolonged ischemia in lung transplantation. Methods: Rat single-lung transplantation was performed in 4 experimental gr oups (n = 5 each). In all groups, transplantation was performed after IS ho urs of cold (4 degrees C) ischemia. All donor lungs were flushed with low-p otassium dextran-glucose (LPDG) solution that also contained 500 mug/liter prostaglandin estradiol (E-1). Groups studied included: Group I: flush solu tion was administered containing 10(-6) mol/liter trimetazidine (TMZ), neit her donor nor recipient treatment given; Group II: donors were treated with 5 mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solutio n did not contain TMZ; Group III: recipients treated with 5 mg/kg intraveno us = 10 minutes before reperfusion, and flush solution contained 10-6 mol/l iter trimetazidine; Group IV: ischemic control group. After 2 hours of repe rfusion, oxygenation was measured and lung tissue was frozen and assessed f or adenosine triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (TBARS). Peak airway pressure (Paw P) was recorded throughout the reperfusion. period. Results: Group III showed significantly higher levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p = 0.008; vs Group II, 4.7 +/ - 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p = 0.008), better oxy genation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5 mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm. Hg, p 0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I, 1.04 +/- 0.76 mnol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0 .4 nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups. Conclusion: Recipient treatment with TMZ provided significant protection of energy status, better oxygenation and reduced lipid peroxidation. Our data suggest that TMZ may be an important adjunct in the prevention of post-tra nsplant lung ischemia-reperfusion injury.