EFFECT OF TROLOX-C ON CARDIAC CONTRACTURE INDUCED BY HYDROGEN-PEROXIDE

Hydrogen peroxide (H2O2) perfused into the aorta of the isolated rat h eart induces a positive inotropic effect, with cardiac arrhythmia such as extrasystolic potentiation or cardiac contractures, depending on t he dose. The last effect is similar to the ''stone heart'' observed in reperfusion injury and may be ascribed to lipoperoxidation (LPO) of t he membrane lipids, to protein damage, to reduction of the ATP level, to enzymatic alterations and to cardioactive compounds liberated by LP O. These effects may result in calcium overload of the cardiac fibers and contracture (''stone heart''). Hearts from male Wistar rats (300-3 50 g) were perfused at 31 degrees C with Tyrode, 0.2 mM trolox C, 256 mM H2O2 or trolox C + H2O2. Cardiac contractures (baseline elevation o f the myograms obtained) were observed when hearts were perfused with H2O2 (Tyrode: 5.9 +/- 3.2; H2O2: 60.5 +/- 13.9% of the initial value); perfusion with H2O2 increased the LPO of rat heart homogenates measur ed by chemiluminescence (Tyrode: 3,199 +/- 259; H2O2: 5,304 +/- 133 cp s mg protein(-1) 60 min(-1)), oxygen uptake (Tyrode: 0.44 +/- 0.1; H2O 2: 3.2 +/- 0.8 nmol min(-1) mg protein(-1)) and malonaldehyde (TBARS) formation (Tyrode: 0.12 +/- 0; H2O2: 0.37 +/- 0.1 nmol/ml). Previous p erfusion with 0.2 mM trolox C reduced the LPO (chemiluminescence: 4,09 8 +/- 531), oxygen uptake (0.51 +/- 0) and TBARS (0.13 +/- 0) but did not prevent the H2O2-induced contractures (33.3 +/- 16%). ATP (Tyrode: 2.84 +/- 0; H2O2: 0.57 +/- 0) and glycogen levels (Tyrode: 0.46 +/- 0 ; H2O2: 0.26 +/- 0) were reduced by H2O2. Trolox did not prevent these effects (ATP: 0.84 +/- 0 and glycogen: 0.27 +/- 0). Trolox C is known to be more effective than alpha-tocopherol or gamma-tocopherol in red ucing LPO though it lacks the phytol portion of vitamin E to be fixed to the cell membranes. Trolox C, unlike vitamin A, did not prevent the glycogen reduction induced by H2O2. Trolox C induced a positive chron otropic effect that resulted in higher energy consumption. The reducti on of energy level seemed to be more important than LPO in the mechani sm of H2O2-induced contracture.