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 ischemic injury. In this study, we examined the effects of heat shock induced 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 increased 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 1 h of normothermic reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dp/dt, myocardial segmental shortening (%SS), and coronary blood flow. Cellular injury was examined by measuring creatine kinase (CK) release. Biochemical measurements included quantification 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 recovery of LVDP (61% vs 52%), dp/dtmax (52% vs 44%), and segmental shortening (46.2% vs 10%). Myocardial CK release was significantly reduced 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 antioxidant enzymes.
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110.
N
N
Maulik
Z
Z
Wei
X
X
Liu
R M
RM
Engelman
J A
JA
Rousou
D K
DK
Das
D000661:Amphetamine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006358:Hot Temperature; D007036:Hypothermia, Induced; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects*
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D000661:Amphetamine; D002374:Catalase; D013482:Superoxide Dismutase