IMPROVED POSTISCHEMIC VENTRICULAR FUNCTIONAL RECOVERY BY AMPHETAMINE IS LINKED WITH ITS ABILITY TO INDUCE HEAT-SHOCK

Heat shock has been shown to increase the cellular tolerances to ische mic injury. In this study, we examined the effects of heat shock induc ed by amphetamine on postischemic myocardial functional recovery in a setting of coronary revascularization for acute myocardial infarction. Intramuscular injection of amphetamine (3 mg/kg, i.m.) to pigs increa sed the body temperature to 42.5 degrees C within 1 h, and maintained this temperature for an additional 2 h. Fourty h after the amphetamine injection, the pigs were placed on by cardiopulmonary bypass and then isolated, in situ heart preparations were subjected to 1 h of global hypothermic cardioplegic arrest and 1I h of normothermic reperfusion. Postischemic myocardial performance was monitored by measuring left ve ntricular (LV) pressure, its dp/dt, myocardial segmental shortening (% SS), and coronary blood flow. Cellular injury was examined by measurin g creatine kinase (CK) release. Biochemical measurements included quan tification of plasma catecholamines and study of the induction of heat shock gene expression and antioxidative enzymes in the heart tissue. The results of this study indicated significantly greater recovery of LV contractile functions by amphetamine as demonstrated by improved re covery of LVDP (61% vs 52%), dp/dt(max) (52% vs 44%), and segmental sh ortening (46.2% vs 10%). Myocardial CK release was significantly reduc ed in the amphetamine group. Furthermore, amphetamine pretreatment was associated with the induction of heat shock protein (HSP) 27 mRNA and stimulated Cu/Zn-superoxide dismutase and catalase levels, suggesting that amphetamine mediated improved postischemic ventricular recovery might be linked with its ability to induce heat shock and stimulate an tioxidant enzymes.