MYOCARDIAL ADAPTATION TO ISCHEMIA BY OXIDATIVE STRESS-INDUCED BY ENDOTOXIN

In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induce d by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats we re killed, hearts were isolated, and the effects of ischemia-reperfusi on were studied using an isolated working heart preparation. The devel opment of oxidative stress was examined by assessing malonaldehyde pro duction in the heart. The antioxidant defense system was studied by es timating antioxidant enzyme activities and ascorbate- as well as thiol -dependent antioxidant reserve. The results of our study indicated tha t endotoxin induced oxidative stress within 1 h of treatment; the stre ss was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thio l- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin p rovided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by e ndotoxin-induced adaptive modification of the antioxidant defense in t he heart, thereby reducing ischemic-reperfusion injury.