AN ALPHA-TOCOPHEROL ANALOG WITH ANTIOXIDANT ACTIVITY IMPROVES MYOCARDIAL-FUNCTION DURING ISCHEMIA-REPERFUSION IN ISOLATED WORKING RAT HEARTS

Recently, it has been reported that alpha-tocopherol analogues reduce infarct size in vivo in the rat and improve contractility upon reperfu sion following global ischemia in isolated rat hearts. In the present study, we have thus investigated the effects of the hydrophilic alpha- tocopherol analogue MDL 74366 on nonenzymatic lipid peroxidation using a tissue homogenate method and reperfusion-induced arrhythmias follow ing a local ischemia in isolated working rat hearts. Lipoperoxide (LPO ) production was inhibited in a concentration-dependent manner in spon taneous as well as in induced peroxydations. The concentration resulti ng in a 50% inhibition (IC50) was around 2 muM. MDL 74366 treatment ha d no significant effect on baseline heart rate and cardiac output valu es. However, MDL 74366 decreased the incidence of reperfusion arrhythm ias (ventricular tachycardia, VT; ventricular fibrillation, VF). The c oincidence observed between the protective effect of MDL 74366 against tissue LPO formation and the preventive effect of this alpha-tocopher ol analogue in the heart during the ischemia-reperfusion sequence conf irms that vitamin E has beneficial effects against induced oxidative d amage.