Summary
Two medium-sized branches of the left coronary artery were prepared in each of 10 anesthetized open chest dogs for later occlusion. The first artery was occluded during 90 minutes and reperfused thereafter. This occlusion produced the control infarct. Methylprednisolone (50 mg/kg i.v.) was injected, and the second artery was occluded also for 90 minutes and reperfused thereafter. Both infarcts were made visible by staining left ventricular rings with p-nitrobluetetrazolium. Infarct size was compared with the size of the perfusion area, which we obtained from the postmortem angiogram. Both infarcts were equal in size and comprised 50% of the area of perfusion of the occluded artery. Methylprednisolone in a single high dose given prophylactically did not influence infarct size nor any of the measured parameters.
Zusammenfassung
An 10 Hunden wurde die Wirkung von Methylprednisolon auf die Myokarddurchblutung und die resultierende Infarktgröße nach experimentellem Koronarverschluß untersucht. An jedem Herzen wurden hintereinander zwei mittelgroße Äste der linken Koronararterie für 90 min okkludiert und anschließend reperfundiert. Der Verschluß der 1. Arterie erfolgte unter Kontrollbedingungen, es resultierte der Kontrollinfarkt. Vor dem Verschluß der 2. Arterie wurde Methylprednisolon (50 mg/kg Körpergewicht i.v.) injiziert, es resultierte der Testinfarkt. Die hämodynamischen Parameter (LVP, LV-dp/dt, AOP, HR) wurden kontinuierlich registriert, der myokardiale Sauerstoffverbrauch wurde vom Computer mit Hilfe der Bretschneider-Formel kalkuliert. Die myokardiale Durchblutung wurde mit Hilfe der “Tracer microsphere”-Technik bestimmt. Das Gebiet der myokardialen Nekrose wurde mit Hilfe der p-NBT-Färbung definiert, das Perfusionsgebiet wurde mit Hilfe der Post-mortem-Angiographie bestimmt Die Infarktgröße wurde als Quotient aus Nekrose- und Perfusionsgebiet in Prozent ausgedrückt. Die hämodynamischen Bedingungen waren in beiden Verschlußperioden vergleichbar, der Kollateralfluß betrug im Gebiet der Kontrollarterie 13,9±6,2% und im Gebiet der Testarterie 14,5±7,8% der Normaldurchblutung. Die resultierenden Infarktgrößen waren ohne Unterschied, der Kontrollinfarkt betrug 51±22%, der Testinfarkt 48±25%. Durch Methylprednisolon konnte weder der Kollateralfluß noch die resultierende Infarktgröße nach Koronarligatur beeinflußt werden.
Similar content being viewed by others
References
Wildenthal, K.: Lysosomal alterations in ischemic myocardium: result or cause of myocellular injury? J. Mol. Cell. Cardiol.10, 595–603 (1978).
Okuda, M., A. M. Lefer: Lysosomal hypothesis in evolution of myocardial infarction. Subcellular fractionation and electron microscopic cytochemical study. Jap. Heart J.20, 643–656 (1979).
Schaper, J.: Ultrastructure of the myocardium in acute ischemia. In: The Pathology of Myocardial Perfusion. W. Schaper (ed.), pp. 581–673 Elsevier/North-Holland Biomedical Press (Amsterdam, New York, Oxford 1979).
Welman, E., T. J. Peters: Enhanced lysosome fragility in the anoxic perfused guineapig heart: Effects of glucose and mannitol. J. Mol. Cell. Cardiol.9, 101 (1977).
Johnson, A. S., S. R. Scheinberg, R. A. Gersch, H. C. Saltzstein: Effect of cortisone on the size of experimentally produced myocardial infarcts. Circulation7, 224 (1953).
Vyden, J. D., K. Nagasawa, B. Rabinowitz, W. W. Parmley, H. Tomada, E. Corday, H. J. C. Swan: Effects of methylprednisolone administration in acute myocardial infarction. Amer. J. Cardiol.34, 677 (1974).
Barzilai, D., J. Plavnick, A. Hazani: Use of hydrocortisone in the treatment of acute myocardial infarction. Chest61, 488 (1972).
Da Luz, P. L., J. S. Forrester, H. L. Wyatt, G. A. Diamond, M. Chag, H. J. C. Swan: Myocardial reperfusion in acute experimental ischemia: beneficial effects of prior treatment with steroids. Circulation53, 847 (1976).
Hearse, D. J., M. S. Humphrey: Enzyme release during myocardial anoxia: a study of metabolic protection. J. Mol. Cell. Cardiol.7, 463 (1975).
Libby, P., P. R. Maroko, C. M. Bloor, B. E. Sobel, E. Braunwald: Reduction of experimental myocardial infarct size by corticosteroid administration. J. Clin. Invest.52, 599 (1973).
Mac Lean, D., P. R. Maroko, M. C. Fishbein, E. Braunwald: Effects of corticosteroids on myocardial infarct size and healing following experimental coronary occlusion. Amer. J. Cardiol.39, 280 (1977).
Jorrison, J., R. Lawrence, R. Pizzarello, K. Geller, T. Maley, S. Gulotta: Modification of myocardial injury in man by corticosteroid administration. Circulation53, (Suppl. 1), 200 (1976).
Shatney, C. H., D. J. McCarter, R. C. Lillehei: Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction. Amer. J. Cardiol.37, 572 (1976).
Spath, J. A., D. L. Lane, A. M. Lefer: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in cat. Circulat. Res.35, 44 (1974).
Wexler, B. C.: Comparative effects of cortisone, dianabol and enovid on isoprenaline induced myocardial infarction in arteriosclerotic vs nonarteriosclerotic rats. Brit. J. Exp. Path.57, 663 (1976).
Schaper, W., M. Hofmann, K. D. Müller, K. Genth, M. Carl: Experimental occlusion of two small coronary arteries in the same heart. A new validation method for infarct size manipulation. Basic Res. Cardiol.74, 224–229 (1979).
Schaper, W., J. Frenzel, W. Hort: Experimental coronary artery occlusion. I. Measurement of infaret size. Basic Res. Cardiol.74, 46–53 (1979).
Bretschneider, H. J.: Die hämodynamischen Determinanten des myokardialen Sauerstoffverbrauchs. In: Die therapeutische Anwendung Beta-sympathikolytischer Stoffe. p. 45 H. J. Dengler, Hrsg. Schattauer (Stuttgart-New York 1972).
Lewi, P. J., W. Schaper, D. G. van Riel, W. W. Braet, L. H. Snoeks W. J. Flameng, R. F. Nyens: The use of a minicomputer in cardiovascular pharmacology. Arzneimittelfschg.23, 436 (1973).
Winkler, B., J. Mulch, W. Flameng, W. Schaper: Prediction of MVO2 from the pressure pulse in acute coronary occlusion and following reflow after aortic cross-clamping. Pflügers Arch.368, R-18 (1977).
Nachlas, M. M., T. K. Shnitka: Macroscopic identification of early myocardial infarcts by alterations in dehydrogenase activity. Amer. J. Pathol.42, 379 (1963).
Opie, L. H.: Myocardial infarct size. Part I. Basic considerations. Amer. Heart J.100, 355 (1980).
Jonnings, R. B., K. H. Hawkins, J. E. Lowe, M. L. Hill, S. Klotman, K. A. Reimer: Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. Amer. J. Pathol.92, 187 (1978).
Welman, E., A. P. Selwyn, K. M. Fox: Plasma lysosomal enzyme activity and the assessment of cell death in acute myocardial infarction. In: Advances in Clinical Cardiology Vol. 1, Quantification of Myocardial Ischemia, H. W. Heiss (ed.), G. Witzstrock Publ. (New York 1980).
Nunez, R., E. Calva, M. Marsch, E. Briones, F. López-Soriano: NAD glycohydrolase activity in hearts with acute experimental infarction. Amer. J. Physiol.231, 1173–1177 (1976).
Weissmann, G.: Effects of corticosteroids on the stability and fusion of biomembranes. In: Asthma, Ed. Lichtenstein, L., Austin, K. F., New York, London, Academic Press, p. 221 (1973).
Weissmann, G., S. Hoffstein, H. Kaplan: Early lysosomal disruption in myocardial infarction and protection by methylprednisolone. Clin Res.23, 383 (1975).
Feola, M., M. Rovetto, R. Soriano: Glucocorticoid protection of the myocardial cell membrane and the reduction of edema in experimental acute myocardial ischemia. J. Thorac. Cardiovasc. Surg.72, 631 (1976).
Hoffstein, S., G. Weissmann, A. Fox: Lysosomes in myocardial infarction studies by means of cytochemistry and subcellular fractionation with observations on the effects of methylprednisolone. Circulation53, 34 (1976).
Braunwald, E., P. R. Maroko: Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. Amer. J. Cardiol.37, 550 (1976).
Masters, T. N., N. B. Harbold, D. G. Hall, R. D. Jackson, D. C. Mullen, H. K. Daugherty, F. Robicsek: Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia. Amer. J. Cardiol.37, 577 (1976).
Osher, J., T. Lang, S. Meerbaum, K. Hashimoto, J. Farcot, E. Corday: Methylprednisolone treatment in acute myocardial infarction: effect on regional and global myocardial function. Amer. J. Cardiol.37, 564 (1976).
Bulkley, B. H., W. C. Roberts: Steroid therapy during acute myocardial infarction-a cause of delayed healing and of ventricular aneurysm. Amer. J. Med.56, 244 (1974).
Mac Lean, D., P. R. Maroko, M. C. Fishbein, E. Braunwald: Effects of corticosteroids on myocardial infarct size and healing following experimental coronary occlusion. Amer. J. Cardiol.39, 280 (1977).
Kloner, R. A., M. C. Fishbein, H. Lew, P. R. Maroko, E. Braunwald: Mummification of the infarcted myocardium by high dose corticosteroids. Circulation57, 56 (1978).
Schaper, W.: Residual perfusion of acutely ischemic heart muscle. In: The Pathophysiology of Myocardial Perfusion. W. Schaper (ed.) pp. 345–378. Elsevier/North-Holland Biomedical Press (Amsterdam, New York, Oxford 1979).
Schaper, W., H. Frenzel, W. Hort, B. Winkler: Experimental coronary artery occlusion. II. Spatial and temporal evolution of infarcts in the dog heart. Basic Res. Cardiol.74, 233–239 (1979).
Hofmann, M., M. Hofmann, K. Genth, W. Schaper: The influence of reperfusion on infarct size after experimental coronary artery occlusion. Basic Res. Cardiol.75, 572–582 (1980).
Müller, K. D., H. Klein, W. Schaper: Changes in myocardial oxygen consumption 45 minutes after experimental coronary occlusion do not alter infarct size. Cardiovasc. Res.14, 710–718 (1980).
DeBoer, L. W., H. W. Strauss, R. A. Kloner, R. E. Rude, R. F. Davis, P. R. Maroko, E. Braunwald: Autoradiographic method for measuring the ischemic myocardium at risk: effects of verapamil on infarct size after experimental coronary artery occlusion. Proc. Natl. Acad. Sci. USA77, 6119–6123 (1980).
Lowe, J. E., K. A. Reimer, R. B. Jennings: Infarct size as a function of the amount of myocardium at risk. Amer. J. Pathol.90, 363 (1978).
Vogel, M. W., V. G. Zannoni, G. D. Abrams, B. R. Lucchesi: Inability of methylprednisolone sodium succinate to decrease infarct size or preserve enzyme activity measured 24 hours after coronary occlusion in dog. Circulation55, 588 (1977).
Roberts, R., V. de Mello, B. E. Sobel: Deleterious effects of methylprednisolone in patients with myocardial infarction. Circulation53 (Suppl. I), 204 (1976).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Genth, K., Hofmann, M. & Schaper, W. Ineffectiveness of methylprednisolone to reduce infarct size in experimental coronary occlusion. Basic Res Cardiol 77, 182–187 (1982). https://doi.org/10.1007/BF01908171
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01908171