DRUG-INDUCED HEAT-SHOCK PRECONDITIONING IMPROVES POSTISCHEMIC VENTRICULAR RECOVERY AFTER CARDIOPULMONARY BYPASS

Background Heat-stress preconditioning of mammalian heart has been fou nd to confer protection against ischemic reperfusion injury. Heat shoc k is generally provided by warming the animal by mechanical means, whi ch is often impractical in a clinical setting. Amphetamine, a sympatho mimetic drug, can elevate the body temperature as a result of enhanced endogenous lipolysis. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial recovery in a setting of coronary revascularization for acute myocardial infarction. Methods and Results Adult Yorkshire swine were injected with amphetam ine (3 mg/kg IM) (n=12), and body temperature was continuously monitor ed. For control studies, the pigs were injected with saline (n=12). Fi ve swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hour s, the remaining 7 pigs in each group were placed on cardiopulmonary b ypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery fo llowed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by m easuring left ventricular (LV) pressure, its dP/dt, myocardial segment shortening, and coronary blood flow. Cellular injury was examined by measurement of creatine kinase release. The antioxidant enzymes supero xide dismutase and catalase were also assayed. Amphetamine treatment w as associated with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital organs, including heart, lung, liver, kidney, and brain. Amphetamine also enhanced superoxide dismutase and catalase act ivities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV dev eloped pressure (61% versus 52%), LV dP/dt(max) (52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase rele ase in the amphetamine group. Conclusions The results demonstrate that amphetamine can induce whole-body heat shock that can precondition th e heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditio ning.