Basic Research in Cardiology

, Volume 86, Issue 1, pp 40–48 | Cite as

Exercise training, indomethacin, and isoproterenol-induced myocardial necrosis in the rat

  • G. R. Brodowicz
  • D. R. Lamb
Original Contributions


It was hypothesized that endurance exercise training would attenuate isoproterenol-induced myocardial necrosis in the rat by increasing the concentration of prostacyclin in the myocardial vasculature. Rats were randomly assigned to exercise and control groups. Exercisers ran on a motorized treadmill 1 h · d−1, 5 d · week−1 for 14 weeks. Immediately following the training program subgroups of rats were injected with 4 mg · kg−1 indomethacin or saline. One day later, all rats were given a subcutaneous injection of isoproterenol (20 mg · kg−1); after another 24h they were sacrificed. A decrease of myocardial creatine kinase (CK) activity was used as a marker for myocardial necrosis. Endurance exercise training attenuated the isoproterenol-induced decrease in myocardial CK relative to control by approximately 37% (exercise: 16.4 ± 0.6 U · mg−1 protein; control: 10.5 ± 0.6 U · mg−1 protein; p < 0.05). Pretreatment with indomethacin decreased myocardial CK in the exercise-trained rats (indomethacin: 15.4 ± 0.8 U · mg−1 protein; saline: 17.7 ± 0.7 U · mg−1 protein; p < 0.05), but not in the controls (indomethacin: 10.3 ± 1.0 U · mg−1 protein; saline: 10.8 ± 0.6 U · mg−1 protein; p > 0.05). The concentration of myocardial 6-keto-PGF a marker for prostacyclin, was not altered by exercise but, as expected, was reduced by indomethacin pretreatment (p < 0.05). Thus, exercise training reduces myocardial damage caused by isoproterenol, but the evidence does not support the hypothesis that prostacyclin mediated this effect of training. Further research is needed to determine the extent to which exercise training-induced alterations in sensitivity to PGI2 or TXA2 affect myocardial damage from isoproterenol. The effect of any exercise-induced alteration in cardiac β-adrenoceptor number or binding characteristics which result in myocardial resistance to isoproterenol also cannot be overlooked.

Key words

exercise isoproterenol myocardialnecrosis prostacyclin indomethacin 


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  1. 1.
    American Heart Association (1985) 1986 Heart Facts. Dallas: American Heart AssociationGoogle Scholar
  2. 2.
    Araki H, Lefer A (1980) Role of prostacyclin in the preservation of ischemic myocardial tissue in the perfused cat heart. Circ Res 47:757–763Google Scholar
  3. 3.
    Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254Google Scholar
  4. 4.
    Chance B, Williams G (1955) A simple and rapid assay of oxidative phosphorylation. Nature 175:1120–1121Google Scholar
  5. 5.
    Darrah M, Engen R (1982) Beneficial effects of exercise on l-isoproterenol induced myocardial infarction in male rats. Med Sci Sports Exerc 14:76–80Google Scholar
  6. 6.
    David H, Goos H, Nohring J, Lindenau K, Behrisch D (1985) Ultrastructural morphometric examinations on the protection provided by prostacyclin against myocardial ischaemia. Exp Pathol 27:163–169Google Scholar
  7. 7.
    Demers L, Harrison T, Halbert D, Santen R (1981) Effect of prolonged exercise on plasma prostaglandin levels. Prostaglandins Med 6:413–418Google Scholar
  8. 8.
    Fagard R, Grauwels R, Groeseneken D, Lijnen P, Staessen J, Vanhees L, Amery A (1985) Plasma levels of renin, angiotensin II, and 6-ketoprostaglandin F. in endurance athletes. J Appl Physiol 59:947–952Google Scholar
  9. 9.
    Fitts R, Booth F, Winder W, Holloszy J (1975) Skeletal muscle respiratory capacity, endurance, and glycogen utilization. Am J Physiol 228:1029–1033Google Scholar
  10. 10.
    Gleeson T, Mullin W, Baldwin K (1983) Cardiovascular responses to treadmill exercise in rats: effects of training. J Appl Physiol 54:789–793Google Scholar
  11. 11.
    Grollman S, Costello L (1972) Effect of age and exercise on lipid content of various tissues of the male albino rat. J Appl Physiol 32:761–765Google Scholar
  12. 12.
    Hammond H, White F, Brunton L, Longhurst J (1987) Association of decreased myocardial β-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise. Circ Res 60:720–726Google Scholar
  13. 13.
    Hashimoto H, Kai I, Sakai K, Ito T, Ogawa K, Satake T (1980) Effects of aspirin, indomethacin, sulfinpyrazone and propranolol on the isoproterenol-induced necrosis. In: Forster W, Sarembe B, Mentz P (eds) Prostaglandins and thromboxanes; VEB Gustav Fischer Verlag, Jena, pp 27–32Google Scholar
  14. 14.
    Johnston K, MacLeod B, Walker M (1983) Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size. Br J Pharmacol 78:29–37Google Scholar
  15. 15.
    Jugdutt B (1981) Effect of PGE1, PGE2 and PGI2 on ventricular arrhythmias during myocardial infarction in conscious dogs: relation to infarct size. Prostaglandins Med 7:431–435Google Scholar
  16. 16.
    Kanter M, Hamlin R, Unverferth D, Davis H, Merola A (1985) Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin. J Appl Physiol 59:1298–1303Google Scholar
  17. 17.
    Kjekshus J, Sobel B (1975) Depressed myocardial creatine phosphokinase activity following experimental myocardial infarction in rabbit. Circ Res 27:403–414Google Scholar
  18. 18.
    Maroko P, Braunwald E (1975) Effects of metabolic and pharmacological interventions on myocardial infarct size following coronary occlusion. Acta Med Scand (Suppl) 587:125–134Google Scholar
  19. 19.
    Maroko P, Deboer L, Davis R (1980) Infarct size reduction: a critical review. Adv Cardiol 27:127–169Google Scholar
  20. 20.
    McElroy C, Gissen S, Fishbein M (1978) Exercise-induced reduction in myocardial infarct size after coronary artery occlusion in rats. Circulation 57:958–962Google Scholar
  21. 21.
    Melin J, Becker L (1983) Salvage of ischemic myocardium by prostacyclin during experimental myocardial infarction. J Am Coll Cardiol 2:279–286Google Scholar
  22. 22.
    Merola A, Gillespie A, Karpen C, Panganamala R, Davis H (1984) Prostaglandin response in the exercise conditioned rat. Prostaglandins Leukotrienes Med 14:169–174Google Scholar
  23. 23.
    Moore R, Riedy M, Gollnick P (1982) Effect of training on β-adrenergic receptor number in rat heart. J Appl Physiol 52:1133–1137Google Scholar
  24. 24.
    Mraz M, Faltova E, Lincova D, Sedivy J, Gaier N, Muhlbachova E, Cernohorsky M, Vrana A (1986) Genetic differences in the resistance of rats to isoprenaline-induced heart lesions. Basic Res Cardiol 81:74–82Google Scholar
  25. 25.
    Nutter D, Priest R, Fuller E (1981) Endurance training in the rat. I. Myocardial mechanics and biochemistry. J Appl Physiol 51:934–940Google Scholar
  26. 26.
    Oscai L, Mole P, Brei B, Holloszy J (1971) Cardiac growth and respiratory enzyme levels in male rats subjected to a running program. Am J Physiol 220:1238–1241Google Scholar
  27. 27.
    Persoon-Rothert M, van der Valk-Kokshoorn E, Egas-Kenniphaas J, Mauve I, van der Laarse A (1989) Isoproterenol-induced cytotoxicity in neonatal rat heart cell cultures is mediated by free radical formation. J Mol Cell Cardiol 21:1285–1291Google Scholar
  28. 28.
    Powell W (1980) Rapid extraction of oxygenated metabolites of arachidonic acid from biological samples using octadecylsilyl silica. Prostaglandins 20:947–957Google Scholar
  29. 29.
    Richard V, Pestre S, deLeiris J (1983) Pharmacological reduction of infarct size in the rat. J Mol Cell Cardiol 15:18Google Scholar
  30. 30.
    Riggs C, Landiss C, Jessup G, Bonner H (1977) Effects of exercise on the severity of isoproterenol-induced myocardial infarction. Med Sci Sports 9:83–87Google Scholar
  31. 31.
    Rosalki S (1967) An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 69:696–705Google Scholar
  32. 32.
    Rude R, Muller J, Braunwald E (1981) Efforts to limit the size of myocardial infarcts. Ann Intern Med 95:736–761Google Scholar
  33. 33.
    Schaible T, Scheuer J (1985) Cardiovascular adaptations to chronic exercise. Prog Cardiovasc Dis 27:297–324Google Scholar
  34. 34.
    Scheuer J, Stezoski S (1972) Effect of physical training on the mechanical and metabolic response of the rat heart to hypoxia. Circ Res 30:418–429Google Scholar
  35. 35.
    Scheffer M, Verdouw P (1983) Decreased incidence of ventricular fibrillation after acute coronary artery ligation in exercised pigs. Basic Res Cardiol 789:298–309Google Scholar
  36. 36.
    Sylvestre-Gervais L, Nadeau A, Nguyen M, Tancrede G, Rousseau-Migneron S (1982) Effects of physical training on β-adrenergic receptors in rat myocardial tissue. Cardiovasc Res 16:530–534Google Scholar
  37. 37.
    Tada M, Hoshida S, Kuzuya T, Inove M, Minamino T, Abe H (1985) Augmented thromboxane A2 generation and efficacy of its blockade in acute myocardial infarction. Int J Cardiol 8:301–312Google Scholar
  38. 38.
    Viinikka L, Vuori J, Ylikorkala O (1984) Lipid peroxides, prostacyclin, and thromboxane A2 in runners during acute exercise. Med Sci Sports Exerc 16:275–277Google Scholar
  39. 39.
    Werle E, Strobel G, Weicker H (1990) Decrease in rat cardiac β1- and β2-adrenoceptors by training and endurance exercise. Life Sciences 46:9–17Google Scholar
  40. 40.
    Wexler B (1985) Prolonged protective effects following propranolol withdrawal against isoproterenol-induced myocardial infarction in normotensive and hypertensive rats. Br J Pathol 66:143–154Google Scholar
  41. 41.
    Williams R, Schaible T, Bishop T, Morey M (1984) Effects of endurance training on cholinergic and adrenergic receptors of rat heart. J Mol Cell Cardiol 16:395–403Google Scholar

Copyright information

© Steinkopff Verlag 1991

Authors and Affiliations

  • G. R. Brodowicz
    • 1
    • 2
  • D. R. Lamb
    • 1
  1. 1.Exercise Physiology LaboratoryThe Ohio State UniversityColumbusUSA
  2. 2.Exercise Physiology Laboratory, School of HPEPortland State UniversityPortlandUSA

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