MYOCARDIAL SALVAGE BY TROLOX AND ASCORBIC-ACID, BUT NOT ASCORBIC-ACID ALONE, IN ANESTHETIZED DOGS AND RABBITS

The myocardial salvaging properties of Trolox (Trlx; a water- and lipid-soluble vitamin E analog with antioxidant properties) and ascorbic acid (Asc; a water-soluble antioxidant) were evaluated in anesthetized male dogs and rabbits. Myocardial infarction (MI) was induced by occlusion and reperfusion of the left anterior descending coronary artery: a 2-hr occlusion and 4-hr reperfusion in dogs, and a 15-min occlusion and 3-hr reperfusion in rabbits. This occlusion/reperfusion protocol induced %MI (MI normalized to area at risk) of approximately 20% beyond that induced by occlusion alone in both species. Trlx, Asc (100 and 150 mg/kg/injection, respectively, by injection; or 100 and 150 mg/kg/min, respectively, by continuous infusion), or vehicle (Veh) were administered into the ascending aorta in dogs and into the left atrium in rabbits. In severely ischemic dogs (myocardial collateral blood flow < 0.1 ml/min/g), a single injection of Trlx plus Asc, but not Asc alone, at the onset of reperfusion reduced %MI (Trlx + Asc = 24.3 +/- 5.4%, n = 7; Asc = 50.1 +/- 9.6%, n = 4; Veh = 45.0 +/- 5.0%, n = 5). In rabbits, %MI was reduced (or tended to be reduced) by either 3 hourly injections (Trlx + Asc = 33.3 +/- 4.0%, n = 19; Asc = 48.3 +/- 6.3%, n = 11; Veh = 43.7 +/- 3.3%, n = 8) or an injection followed by continuous infusion (Trlx + Asc = 36.0 +/- 4.0%, n = 9; Veh = 49.0 +/- 3.0%, n = 8), beginning at the onset of reperfusion. %MI in rabbits was not affected by either hourly injections beginning from 1 hr after, or a single injection at 1-3x the dosages (i.e., 160-300 and 150-450 mg/kg for Trlx and Asc, respectively), during onset of reperfusion. Hemodynamic variables (arterial pressure, heart rate, rate-pressure-product and left ventricular contractility) were similar among all treatment groups in both species. In conclusion, Trlx/Asc combination, but not Asc alone, reduces %MI in dogs and rabbits. The salvaging effects of Trlx/Asc are unrelated to any changes in hemodynamics. These results are consistent with the hypothesis that lipid peroxidation is involved in myocardial reperfusion injury.