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Drug-induced heat-shock preconditioning improves postischemic ventricular recovery after cardiopulmonary bypass. 1995

N Maulik, and R M Engelman, and Z Wei, and X Liu, and J A Rousou, and J E Flack, and D W Deaton, and D K Das
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.

BACKGROUND Heat-stress preconditioning of mammalian heart has been found to confer protection against ischemic reperfusion injury. Heat shock is generally provided by warming the animal by mechanical means, which is often impractical in a clinical setting. Amphetamine, a sympathomimetic 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. RESULTS Adult Yorkshire swine were injected with amphetamine (3 mg/kg IM) (n = 12), and body temperature was continuously monitored. For control studies, the pigs were injected with saline (n = 12). Five swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs in each group were placed on cardiopulmonary bypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery followed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by measuring 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 superoxide dismutase and catalase were also assayed. Amphetamine treatment was 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 activities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV developed pressure (61% versus 52%), LV dP/dtmax (52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase release in the amphetamine group. CONCLUSIONS The results demonstrate that amphetamine can induce whole-body heat shock that can precondition the heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditioning.

UI MeSH Term Description Entries
D008297 Male Males
D001831 Body Temperature The measure of the level of heat of a human or animal. Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D003326 Coronary Circulation The circulation of blood through the CORONARY VESSELS of the HEART. Circulation, Coronary
D003402 Creatine Kinase A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. Creatine Phosphokinase,ADP Phosphocreatine Phosphotransferase,ATP Creatine Phosphotransferase,Macro-Creatine Kinase,Creatine Phosphotransferase, ATP,Kinase, Creatine,Macro Creatine Kinase,Phosphocreatine Phosphotransferase, ADP,Phosphokinase, Creatine,Phosphotransferase, ADP Phosphocreatine,Phosphotransferase, ATP Creatine
D005260 Female Females
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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