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Improved postischemic ventricular functional recovery by amphetamine is linked with its ability to induce heat shock

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Abstract

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°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.

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References

  1. Burdon RH: Heat shock and heat shock proteins Biochem J 240: 313–324, 1986

    Google Scholar 

  2. Subjeck JR, Shyy TT: Stress protein systems of mammalian cells. Am J Physiol 250: C1-C17, 1986

    Google Scholar 

  3. Lindquist S: The heat shock response Annu Rev Biochem 55: 1151–1191, 1986

    Google Scholar 

  4. Hightower LE: Heat shock, stress proteins, chaperones, and proteotoxicity. Cell 66: 191–197, 1991

    Google Scholar 

  5. Morimoto RI, Tissieres A, Geogopoulos C: Stress Proteins in Biology and Medicine. Cold Spring Harbor Laboratory Press, 1990, pp 1–36

  6. Cairo G, Bardella L, Schiaffonati, Bernell-zazzer A: Synthesis of heat shock proteins in rat liver after ischemia and hyperthermia. Hepatology 5: 357–361, 1985

    Google Scholar 

  7. Currie RW: Synthesis of stress-induced proteins in isolated and perfused rat hearts. Biochem Cell Biol 64: 418–426, 1986

    Google Scholar 

  8. Currie RW, Karmazyn M, Kloc M, Mailer K: Heat shock response is associated with enhanced postischemic ventricular recovery. Circ Res 63: 543–549, 1988

    Google Scholar 

  9. Perdrizet GA, Heffron TG, Buckingham FC, Salciunas PJ, Gaber AO, Stuart FP, Thistlethwaite JR: Stress conditioning: A novel approach to organ preservation. Cur Surg 46: 23–26, 1989

    Google Scholar 

  10. Liu X, Engelman RM, Moraru II, Rousou JA, Flack III JE, Deaton DW, Maulik N, Das DK: Heat shock: A new approach for myocardial preservation in cardiac surgery. Circulation 86 (supp II): 358—363, 1992

    Google Scholar 

  11. Otani H, Engelman RM, Rousou JA, Breyer RH, Clement R, Prasad R, Klar J, Das DK: Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization. J Thorac Cardiovasc Surg 97: 267–276, 1989

    Google Scholar 

  12. Das DK, Engelman RM, Kimura Y: Molecular adaptation of cellular defences following preconditioning of the heart by repeated ischemia. Cardiovasc Res 27: 578–584,1993

    Google Scholar 

  13. Lu D, Maulik N, Moraru II, Kreutzer DL, Das DK: Molecular adaptation of vascular endothelial cells to oxidative stress. Am J Physiol (Cell) 264: C715-C722, 1993

    Google Scholar 

  14. Axelord J, Tomchick R: Increased rate of metabolism of epinephrine and norepinephrine by sympathomimetic amines. J Pharmacol Exp Therapeu 130: 367–374, 1960

    Google Scholar 

  15. Weiss B: Enhancement of performance by amphetamine like drugs. In: T. Sjoquist and M. Tohie (eds). Abuse of Central Stimulants. New York, Raven Press, 1969, pp 31–60

    Google Scholar 

  16. Lu D, Das DK: Induction of differential heatshock gene expression in heart, lung, liver, brain and kidney by a sympathomimetic drug, amphetamine. Biochem Biophys Res Commun 192: 808–812, 1993

    Google Scholar 

  17. Nowak TS, Bond U, Schlesinger MJ: Heat shock RNA levels in brain and other tissues after hyperthermia and transient ischemia. J Neurochem 54: 451–458, 1990

    Google Scholar 

  18. Locke-Winter CR, Winter CB, Nelson DW, Banerjee A: cAMP stimulation facilitates preconditioning against ischemia-reperfusion through norepinephrine and α1 mechanisms. Circulation 84 (suppl II): 433–438, 1991

    Google Scholar 

  19. Knowlton AA, Brecher P, Apstein CS: Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia J Clin Invest 87: 139–147, 1991

    Google Scholar 

  20. Donnelly TJ, Sievers RE, Vissern FLJ, Welch WJ, Wolfe CL: Heat shock protein induction in rat hearts: A role for improved myocardial salvage after ischemia and reperfusion? Circulation 85: 769–778, 1992

    Google Scholar 

  21. Wall SR, Fliss H, Kako KJ, Korecky B: Heat shock does not improve recovery of function after no-flow ischemia in isolated rat hearts. J Mol Cell Cardiol 22 (suppl I): 44, 1990

    Google Scholar 

  22. Yellon DM, Iliodromitis E, Latchman DS, Van Winkle DM, Downey JM, Williams FM, Williams TJ: Whole body heat stress fails to limit infarct size in the reperfused rabbit heart. Cardiovasc Res 26: 342–346, 1992

    Google Scholar 

  23. Salo D, Donovan CM, Davies KJA: HSP 70 and other possible heat shock oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. Free Rad Biol Med 11: 239–246, 1991

    Google Scholar 

  24. Currie RW, Tanguay RM: Analysis of RNA for transcripts for catalase and SP 71 in rat hearts afterin vivo hyperthermia. Biochem Cell Biol 69: 375–382, 1991

    Google Scholar 

  25. Karmazyn M, Mailer K, Currie RW: Acquisition and decay of enhanced post-ischemic ventricular recovery is associated with the heat shock response. Am J Physiol 259: H424–431, 1990

    Google Scholar 

  26. Shedt CA, Hass MA, Massaro D:In vitro heat shock increases the synthesis of Cu−Zn superoxide dismutase in normal mammalian tissue. Proc Fed Am Soc Exp Biol 45: 317–325, 1986

    Google Scholar 

  27. Polla BS: A role for heat shock proteins in inflammation? Immunol Today 9: 134–137, 1988

    Google Scholar 

  28. Das DK, Engelman RM: Mechanism of free radical generation in ischemic and reperfused myocardium. In: D.K. Das, W.B. Essman (ed). Oxygen Radicals: Systemic Events and Disease Processes. CRC Press, Florida, 1989, pp 97–128

    Google Scholar 

  29. Kukreja RC, Hess ML: Oxygen radicals, neutrophil-derived oxidants, and myocardial reperfusion injury. In: D.K. Das (ed). Pathophysiology of reperfusion injury. CRC Press, Florida, 1993, pp 221–242

    Google Scholar 

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Maulik, N., Wei, Z., Liu, X. et al. Improved postischemic ventricular functional recovery by amphetamine is linked with its ability to induce heat shock. Mol Cell Biochem 137, 17–24 (1994). https://doi.org/10.1007/BF00926035

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  • DOI: https://doi.org/10.1007/BF00926035

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