Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 May;79(5):1431–1439. doi: 10.1172/JCI112971

Steroid administration after myocardial infarction promotes early infarct expansion. A study in the rat.

J A Mannisi, H F Weisman, D E Bush, P Dudeck, B Healy
PMCID: PMC424414  PMID: 3571494

Abstract

Whether steroids lead to thinner scars and larger aneurysms by delaying collagen deposition or worsening infarct expansion before significant collagen deposition begins is unknown. Rats underwent either transmural infarction by left coronary ligation or sham operation. Both infarct and sham rats were randomized to methylprednisolone 50 mg/kg i.p. X 4 or saline treatment within 24 h after operation. Sacrifice occurred before (3 d) or after (7 d) collagen deposition typically begins. Despite similar infarct size, infarct wall thickness was 1.35 +/- 0.08 mm in the saline and 0.99 +/- 0.12 mm in the methylprednisolone group (P less than 0.001) at 3 d. This decrease in wall thickness was explained by a decrease in the number of myocytes across the infarct wall (r = 0.99; P less than 0.001), suggesting that steroids promote myocyte slippage. Furthermore, methylprednisolone caused no further infarct thinning or cavity dilatation beyond 3 d. Thus, high-dose methylprednisolone given within 24 h after transmural infarction worsens infarct expansion before collagen is laid down by promoting the slippage of necrotic myocytes.

Full text

PDF
1432

Images in this article

1432Image
on p.1432
1433Image
on p.1433
1433Image
on p.1433
1435Image
on p.1435
1435Image
on p.1435

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bulkley B. H., Roberts W. C. Steroid therapy during acute myocardial infarction. A cause of delayed healing and of ventricular aneurysm. Am J Med. 1974 Feb;56(2):244–250. doi: 10.1016/0002-9343(74)90603-2. [DOI] [PubMed] [Google Scholar]
  2. Caulfield J. B., Borg T. K. The collagen network of the heart. Lab Invest. 1979 Mar;40(3):364–372. [PubMed] [Google Scholar]
  3. Fishbein M. C., Maclean D., Maroko P. R. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am J Pathol. 1978 Jan;90(1):57–70. [PMC free article] [PubMed] [Google Scholar]
  4. Forrester J. S., Diamond G., Parmley W. W., Swan H. J. Early increase in left ventricular compliance after myocardial infarction. J Clin Invest. 1972 Mar;51(3):598–603. doi: 10.1172/JCI106849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein S. Letter: Pacing the WPW patient. Circulation. 1976 Jan;53(1):204–205. doi: 10.1161/01.cir.53.1.204. [DOI] [PubMed] [Google Scholar]
  6. Hammerman H., Kloner R. A., Hale S., Schoen F. J., Braunwald E. Dose-dependent effects of short-term methylprednisolone on myocardial infarct extent, scar formation, and ventricular function. Circulation. 1983 Aug;68(2):446–452. doi: 10.1161/01.cir.68.2.446. [DOI] [PubMed] [Google Scholar]
  7. Hammerman H., Schoen F. J., Braunwald E., Kloner R. A. Drug-induced expansion of infarct: morphologic and functional correlations. Circulation. 1984 Mar;69(3):611–617. doi: 10.1161/01.cir.69.3.611. [DOI] [PubMed] [Google Scholar]
  8. Hochman J. S., Bulkley B. H. Expansion of acute myocardial infarction: an experimental study. Circulation. 1982 Jun;65(7):1446–1450. doi: 10.1161/01.cir.65.7.1446. [DOI] [PubMed] [Google Scholar]
  9. Hochman J. S., Bulkley B. H. Pathogenesis of left ventricular aneurysms: an experimental study in the rat model. Am J Cardiol. 1982 Jul;50(1):83–88. doi: 10.1016/0002-9149(82)90012-1. [DOI] [PubMed] [Google Scholar]
  10. Hood W. B., Jr, Bianco J. A., Kumar R., Whiting R. B. Experimental myocardial infarction. IV. Reduction of left ventricular compliance in the healing phase. J Clin Invest. 1970 Jul;49(7):1316–1323. doi: 10.1172/JCI106347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kloner R. A., Fishbein M. C., Lew H., Maroko P. R., Braunwald E. Mummification of the infarcted myocardium by high dose corticosteroids. Circulation. 1978 Jan;57(1):56–63. doi: 10.1161/01.cir.57.1.56. [DOI] [PubMed] [Google Scholar]
  12. Kolata G. The Proper Display of Data: Two statisticians looked at graphs in scientific publications and they suggest means of improvement. Science. 1984 Oct 12;226(4671):156–157. doi: 10.1126/science.226.4671.156. [DOI] [PubMed] [Google Scholar]
  13. Linzbach A. J. Hypertrophy, hyperplasia and structural dilatation of the human heart. Adv Cardiol. 1976;18(0):1–14. doi: 10.1159/000399507. [DOI] [PubMed] [Google Scholar]
  14. Maclean D., Fishbein M. C., Braunwald E., Maroko P. R. Long-term preservation of ischemic myocardium after experimental coronary artery occlusion. J Clin Invest. 1978 Mar;61(3):541–551. doi: 10.1172/JCI108965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Osher J., Lang T. W., Meerbaum S., Hashimoto K., Farcot J. C., Corday E. Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function. Am J Cardiol. 1976 Mar 31;37(4):564–571. doi: 10.1016/0002-9149(76)90397-0. [DOI] [PubMed] [Google Scholar]
  16. Pirzada F. A., Ekong E. A., Vokonas P. S., Apstein C. S., Hood W. B., Jr Experimental myocardial infarction. XIII. Sequential changes in left ventricular pressure-length relationships in the acute phase. Circulation. 1976 Jun;53(6):970–975. doi: 10.1161/01.cir.53.6.970. [DOI] [PubMed] [Google Scholar]
  17. Reimer K. A., Jennings R. B. The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation. Circulation. 1979 Oct;60(4):866–876. doi: 10.1161/01.cir.60.4.866. [DOI] [PubMed] [Google Scholar]
  18. Schuster E. H., Bulkley B. H. Expansion of transmural myocardial infarction: a pathophysiologic factor in cardiac rupture. Circulation. 1979 Dec;60(7):1532–1538. doi: 10.1161/01.cir.60.7.1532. [DOI] [PubMed] [Google Scholar]
  19. Sonnenblick E. H., Ross J., Jr, Covell J. W., Spotnitz H. M., Spiro D. The ultrastructure of the heart in systole and diastole. Chantes in sarcomere length. Circ Res. 1967 Oct;21(4):423–431. doi: 10.1161/01.res.21.4.423. [DOI] [PubMed] [Google Scholar]
  20. Spotnitz H. M., Spotnitz W. D., Cottrell T. S., Spiro D., Sonnenblick E. H. Cellular basis for volume related wall thickness changes in the rat left ventricle. J Mol Cell Cardiol. 1974 Aug;6(4):317–331. doi: 10.1016/0022-2828(74)90074-1. [DOI] [PubMed] [Google Scholar]
  21. Vinegar R., Schreiber W., Hugo R. Biphasic development of carrageenin edema in rats. J Pharmacol Exp Ther. 1969 Mar;166(1):96–103. [PubMed] [Google Scholar]
  22. Vogel W. M., Zannoni V. G., Abrams G. D., Lucchesi B. R. Inability of methylprednisolone sodium succinate to decrease infarct size or preserve enzyme activity measured 24 hours after coronary occlusion in the dog. Circulation. 1977 Apr;55(4):588–595. doi: 10.1161/01.cir.55.4.588. [DOI] [PubMed] [Google Scholar]
  23. Vyden J. K., Nagasawa K., Rabinowitz B., Parmley W. W., Tomoda H., Corday E., Swan H. J. Effects of methylprednisolone administration in acute myocardial infarction. Am J Cardiol. 1974 Nov;34(6):677–686. doi: 10.1016/0002-9149(74)90157-x. [DOI] [PubMed] [Google Scholar]
  24. Weibel E. R. Selection of the best method in stereology. J Microsc. 1974 Apr;100(3):261–269. doi: 10.1111/j.1365-2818.1974.tb03938.x. [DOI] [PubMed] [Google Scholar]
  25. Weisman H. F., Bush D. E., Mannisi J. A., Bulkley B. H. Global cardiac remodeling after acute myocardial infarction: a study in the rat model. J Am Coll Cardiol. 1985 Jun;5(6):1355–1362. doi: 10.1016/s0735-1097(85)80348-x. [DOI] [PubMed] [Google Scholar]
  26. Wiener S. L., Wiener R., Urivetzky M., Shafer S., Isenberg H. D., Janov C., Meilman E. The mechanism of action of a single dose of methylprednisolone on acute inflammation in vivo. J Clin Invest. 1975 Sep;56(3):679–689. doi: 10.1172/JCI108138. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES