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. 1973 Mar;52(3):599–607. doi: 10.1172/JCI107221

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Peter Libby 1,2,3,4, Peter R Maroko 1,2,3,4, Colin M Bloor 1,2,3,4, Burton E Sobel 1,2,3,4, Eugene Braunwald 1,2,3,4
PMCID: PMC302298  PMID: 4685084

Abstract

The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (S̄T̄) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronary occlusion. In the control group S̄T̄ and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, S̄T̄ fell from 3.5±0.8 to 1.1±0.4 mV (P<0.01) and NST was reduced from 6.7±1.1 to 1.4±0.8 (P<0.01). In order to study the influence of hydrocortisone on necrosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N = 102 specimens, r = -0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs). Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK = -0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the ½ h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion.

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Selected References

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  1. BEAUFAY H., VAN CAMPENHOUT E., DE DUVE C. Tissue fractionation studies. II. Influence of various hepatotoxic treatments on the state of some bound enzymes in rat liver. Biochem J. 1959 Dec;73:617–623. doi: 10.1042/bj0730617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BREU W. Das Nebennierenrindenhormon in der Behandlung des frischen Myokardinfarktes. Munch Med Wochenschr. 1951 Mar 30;93(13):666–671. [PubMed] [Google Scholar]
  3. Barzilai D., Plavnick J., Hazani A., Einath R., Kleinhaus N., Kanter Y. Use of hydrocortisone in the treatment of acute myocardial infarction. Summary of a clinical trial in 446 patients. Chest. 1972 May;61(5):488–491. doi: 10.1378/chest.61.5.488. [DOI] [PubMed] [Google Scholar]
  4. Buchanan W. E., Schwartz T. B. Lysosomal enzyme activity in heart and skeletal muscle of cortisone-treated rats. Am J Physiol. 1967 Apr;212(4):732–736. doi: 10.1152/ajplegacy.1967.212.4.732. [DOI] [PubMed] [Google Scholar]
  5. CHAPMAN D. W., SKAGGS R. H., THOMAS J. R., GREENE J. A. The effect of cortisone in experimental myocardial infarction. Am J Med Sci. 1952 Jan;223(1):41–44. doi: 10.1097/00000441-195201000-00007. [DOI] [PubMed] [Google Scholar]
  6. Carter J. W., Thomas C. S., Jr The circulatory response to pharmacological levels of hydrocortisone. J Surg Res. 1970 Sep;10(9):437–442. doi: 10.1016/0022-4804(70)90067-3. [DOI] [PubMed] [Google Scholar]
  7. DALL J. L., BUCHANAN J. Steroid therapy in heart-block following myocardial infarction. Lancet. 1962 Jul 7;2(7245):8–12. doi: 10.1016/s0140-6736(62)92930-6. [DOI] [PubMed] [Google Scholar]
  8. DALL J. L., PEEL A. A. A TRIAL OF HYDROCARTISONE IN ACUTE MYOCARDIAL INFARCTION. Lancet. 1963 Nov 23;2(7317):1097–1098. doi: 10.1016/s0140-6736(63)92864-2. [DOI] [PubMed] [Google Scholar]
  9. DALL J. L. THE EFFECT OF STEROID THERAPY ON NORMAL AND ABNORMAL ATRIO-VENTRICULAR CONDUCTION. Br Heart J. 1964 Jul;26:537–543. doi: 10.1136/hrt.26.4.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FISCHER S., 3rd, EDWARDS W. S. TISSUE NECROSIS AFTER TEMPORARY CORONARY ARTERY OCCLUSION. Am Surg. 1963 Sep;29:617–619. [PubMed] [Google Scholar]
  11. FRIEDBERG C. K., KAHN M., SCHEUER J., BLEIFER S., DACK S. Adams-Stokes syndrome associated with chronic heart block. Treatment with corticosteroids. J Am Med Assoc. 1960 Mar 12;172:1146–1152. doi: 10.1001/jama.1960.03020110030008. [DOI] [PubMed] [Google Scholar]
  12. GERISCH R. A., COMPEAU L. Treatment of acute myocardial infarction in man with cortisone. Am J Cardiol. 1958 Apr;1(4):535–536. [PubMed] [Google Scholar]
  13. GREEN J. P. STEROID THERAPY AND WOUND HEALING IN SURGICAL PATIENTS. Br J Surg. 1965 Jul;52:523–525. doi: 10.1002/bjs.1800520710. [DOI] [PubMed] [Google Scholar]
  14. GRIFFITH G. C., WALLACE W. B., COCHRAN B., Jr, NERLICH W. E., FRASHER W. E. The treatment of shock associated with myocardial infarction. Circulation. 1954 Apr;9(4):527–532. doi: 10.1161/01.cir.9.4.527. [DOI] [PubMed] [Google Scholar]
  15. Ginks W. R., Sybers H. D., Maroko P. R., Covell J. W., Sobel B. E., Ross J., Jr Coronary artery reperfusion. II. Reduction of myocardial infarct size at 1 week after the coronary occlusion. J Clin Invest. 1972 Oct;51(10):2717–2723. doi: 10.1172/JCI107091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HEPPER N. G., PRUITT R. D., DONALD D. E., EDWARDS J. E. The effect of cortisone on experimentally produced myocardial infarcts. Circulation. 1955 May;11(5):742–748. doi: 10.1161/01.cir.11.5.742. [DOI] [PubMed] [Google Scholar]
  17. HOOVER M. P., MANNING G. W. The effects of cortisone and ACTH on artificially induced cardiac infarction in the dog. Am Heart J. 1954 Mar;47(3):343–347. doi: 10.1016/0002-8703(54)90291-4. [DOI] [PubMed] [Google Scholar]
  18. Harnarayan C., Bennett M. A., Pentecost B. L., Brewer D. B. Quantitative study of infarcted myocardium in cardiogenic shock. Br Heart J. 1970 Nov;32(6):728–732. doi: 10.1136/hrt.32.6.728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hunt T. K., Ehrlich H. P., Garcia J. A., Dunphy J. E. Effect of vitamin A on reversing the inhibitory effect of cortisone on healing of open wounds in animals and man. Ann Surg. 1969 Oct;170(4):633–641. doi: 10.1097/00000658-196910000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. JOHNSON A. S., SCHEINBERG S. R., GERISCH R. A., SALTZSTEIN H. C. Effect of cortisone on the size of experimentally produced myocardial infarcts. Circulation. 1953 Feb;7(2):224–228. [PubMed] [Google Scholar]
  21. Jennings R. B. Early phase of myocardial ischemic injury and infarction. Am J Cardiol. 1969 Dec;24(6):753–765. doi: 10.1016/0002-9149(69)90464-0. [DOI] [PubMed] [Google Scholar]
  22. LACROIX E., LEUSEN I. The influence of cortisone on the oxygen consumption of myocard and diaphragm slices of the rat. Arch Int Pharmacodyn Ther. 1958 Feb 1;114(1):103–117. [PubMed] [Google Scholar]
  23. Leighty E. G., Stoner C. D., Ressallat M. M., Passananti G. T., Sirak H. D. Effects of acute asphyxia and deep hypothermia on the state of binding of lysosomal acid hydrolases in canine cardiac muscle. Circ Res. 1967 Jul;21(1):59–64. doi: 10.1161/01.res.21.1.59. [DOI] [PubMed] [Google Scholar]
  24. Maroko P. R., Kjekshus J. K., Sobel B. E., Watanabe T., Covell J. W., Ross J., Jr, Braunwald E. Factors influencing infarct size following experimental coronary artery occlusions. Circulation. 1971 Jan;43(1):67–82. doi: 10.1161/01.cir.43.1.67. [DOI] [PubMed] [Google Scholar]
  25. Maroko P. R., Libby P., Covell J. W., Sobel B. E., Ross J., Jr, Braunwald E. Precordial S-T segment elevation mapping: an atraumatic method for assessing alterations in the extent of myocardial ischemic injury. The effects of pharmacologic and hemodynamic interventions. Am J Cardiol. 1972 Feb;29(2):223–230. doi: 10.1016/0002-9149(72)90633-9. [DOI] [PubMed] [Google Scholar]
  26. Maroko P. R., Libby P., Ginks W. R., Bloor C. M., Shell W. E., Sobel B. E., Ross J., Jr Coronary artery reperfusion. I. Early effects on local myocardial function and the extent of myocardial necrosis. J Clin Invest. 1972 Oct;51(10):2710–2716. doi: 10.1172/JCI107090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Maroko P. R., Libby P., Sobel B. E., Bloor C. M., Sybers H. D., Shell W. E., Covell J. W., Braunwald E. Effect of glucose-insulin-potassium infusion on myocardial infarction following experimental coronary artery occlusion. Circulation. 1972 Jun;45(6):1160–1175. doi: 10.1161/01.cir.45.6.1160. [DOI] [PubMed] [Google Scholar]
  28. McConn R., Del Guercio L. R. Respiratory function of blood in the acutely ill patient and the effect of steroids. Ann Surg. 1971 Sep;174(3):436–450. doi: 10.1097/00000658-197109000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Motsay G. J., Alho A., Jaeger T., Dietzman R. H., Lillehei R. C. Effects of corticosteroids on the circulation in shock: experimental and clinical results. Fed Proc. 1970 Nov-Dec;29(6):1861–1873. [PubMed] [Google Scholar]
  30. Nachlas M. M., Siedband M. P. The influence of diastolic augmentation on infarct size following coronary artery ligation. J Thorac Cardiovasc Surg. 1967 May;53(5):698–706. [PubMed] [Google Scholar]
  31. OPDYKE D. F., LAMBERT A., STOERK H. C., ZANETTI M. E., KUNA S. Failure to reduce the size of experimentally produced myocardial infarcts by cortisone treatment. Circulation. 1953 Oct;8(4):544–548. doi: 10.1161/01.cir.8.4.544. [DOI] [PubMed] [Google Scholar]
  32. Oskoui M., Aviado D. M. Bronchopulmonary and cardiac effects of hydrocortisone. Arch Int Pharmacodyn Ther. 1969 Jun;179(2):314–325. [PubMed] [Google Scholar]
  33. Page D. L., Caulfield J. B., Kastor J. A., DeSanctis R. W., Sanders C. A. Myocardial changes associated with cardiogenic shock. N Engl J Med. 1971 Jul 15;285(3):133–137. doi: 10.1056/NEJM197107152850301. [DOI] [PubMed] [Google Scholar]
  34. RAGAN C., HOWES E. L. Effect of cortisone on production of granulation tissue in the rabbit. Proc Soc Exp Biol Med. 1949 Dec;72(3):718-21, illust. doi: 10.3181/00379727-72-17555. [DOI] [PubMed] [Google Scholar]
  35. Ravens K. G., Gudbjarnason S. Changes in the activities of lysosomal enzymes in infarcted canine heart muscle. Circ Res. 1969 Jun;24(6):851–856. doi: 10.1161/01.res.24.6.851. [DOI] [PubMed] [Google Scholar]
  36. Rosalki S. B. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med. 1967 Apr;69(4):696–705. [PubMed] [Google Scholar]
  37. SAMBHI M. P., WEIL M. H., UDHOJI V. N. ACUTE PHARMACODYNAMIC EFFECTS OF GLUCOCORTICOIDS; CARDIAC OUTPUT AND RELATED HEMODYNAMIC CHANGES IN NORMAL SUBJECTS AND PATIENTS IN SHOCK. Circulation. 1965 Apr;31:523–530. doi: 10.1161/01.cir.31.4.523. [DOI] [PubMed] [Google Scholar]
  38. SAVRANOGLU N., BOUCEK R. J., CASTEN G. G. The extent of reversibility of myocardial ischemia in dogs. Am Heart J. 1959 Nov;58:726–731. doi: 10.1016/0002-8703(59)90231-5. [DOI] [PubMed] [Google Scholar]
  39. WEISSMANN G., DINGLE J. Release of lysosomal protease by ultraviolet irradiation and inhibition by hydrocortisone. Exp Cell Res. 1961 Oct;25:207–210. doi: 10.1016/0014-4827(61)90328-7. [DOI] [PubMed] [Google Scholar]
  40. WEISSMANN G., THOMAS L. THE EFFECTS OF CORTICOSTEROIDS UPON CONNECTIVE TISSUE AND LYSOSOMES. Recent Prog Horm Res. 1964;20:215–245. [PubMed] [Google Scholar]
  41. WHEAT M. W., Jr ULTRASTRUCTURE AUTORADIOGRAPHY AND LYSOSOME STUDIES IN MYOCARDIUM. J Mt Sinai Hosp N Y. 1965 Mar-Apr;32:107–121. [PubMed] [Google Scholar]
  42. Watanabe T., Covell J. W., Maroko P. R., Braunwald E., Ross J., Jr Effects of increased arterial pressure and positive inotropic agents on the severity of myocardial ischemia in the acutely depressed heart. Am J Cardiol. 1972 Sep;30(4):371–377. doi: 10.1016/0002-9149(72)90567-x. [DOI] [PubMed] [Google Scholar]
  43. Wilson R. F., Fisher R. R. The hemodynamic effects of massive steroids in clinical shock. Surg Gynecol Obstet. 1968 Oct;127(4):769–776. [PubMed] [Google Scholar]
  44. YABUKI S., BLANCO G., IMBRIGLIA J. E., BENTIVOGLIO L., BAILEY C. P. Time studies of acute, reversible, coronary occlusions in dogs. J Thorac Cardiovasc Surg. 1959 Jul;38(1):40–45. [PubMed] [Google Scholar]

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