OXIDATIVE STRESS-ADAPTATION IMPROVES POSTISCHEMIC VENTRICULAR RECOVERY

Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. in this stud y, the effects of myocardial adaptation to oxidative stress was examin ed by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic deri vative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress w ithin 1 h of treatment as evidenced by enhanced malonaldehyde formatio n. The oxidative stress disappeared steadily and progressively with ti me in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, gl utathione peroxidase and glutathione reductase. After 24 h of endotoxi n or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, comp ared to those at the baseline levels. Corroborating these results, bot h endotoxin and lipid A provided protection against myocardial ischemi a and reperfusion injury as evidenced by significantly improved postis chemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adapta tion to oxidative stress may be a potential tool for reduction of isch emic/reperfusion injury.