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. 1992 Feb;89(2):618–629. doi: 10.1172/JCI115628

Chronic coronary artery constriction leads to moderate myocyte loss and left ventricular dysfunction and failure in rats.

P Anversa 1, X Zhang 1, P Li 1, J M Capasso 1
PMCID: PMC442895  PMID: 1531347

Abstract

Coronary artery narrowing, ranging from 19% to 61%, was induced in rats and ventricular performance, myocardial damage, and myocyte hypertrophy were examined 1 mo later. Animals were separated into two groups, exhibiting ventricular dysfunction and failure, respectively. Dysfunction consisted of a 2.4-fold increase in left ventricular end diastolic pressure (LVEDP), 15% decrease in left ventricular peak systolic pressure (LVPSP), 24% reduction in developed pressure (DP), and a 16% depression in-dP/dt. Failure was defined on the basis of a 4.7-fold elevation in LVEDP, and a 26%, 47%, 45%, and 41% decrease in LVPSP, DP, +dP/dt, and -dP/dt. Moreover, in this group, right ventricular end diastolic and systolic pressures increased 5.5- and 1.2-fold. Left and right ventricular weights expanded 23% and 51% with dysfunction and 30% and 56% with failure. Left ventricular hypertrophy was characterized by ventricular dilation and wall thinning which were more severe in the failing animals. Foci of damage were found in both groups but tissue injury was more prominent in the endomyocardium and in failing rats. Finally, myocyte loss in the ventricle was 10% and 20% with dysfunction and failure whereas the corresponding enlargements of the unaffected myocytes were 34% and 53%. Thus, coronary narrowing led to abnormalities in cardiac dynamics with an increase in diastolic wall stress and extensive ventricular remodeling in spite of a moderate loss of myocytes and compensatory reactive hypertrophy of the viable cells.

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Selected References

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  1. Anversa P., Beghi C., Kikkawa Y., Olivetti G. Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circ Res. 1986 Jan;58(1):26–37. doi: 10.1161/01.res.58.1.26. [DOI] [PubMed] [Google Scholar]
  2. Anversa P., Loud A. V., Levicky V., Guideri G. Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy. Am J Physiol. 1985 Jun;248(6 Pt 2):H876–H882. doi: 10.1152/ajpheart.1985.248.6.H876. [DOI] [PubMed] [Google Scholar]
  3. Anversa P., Palackal T., Sonnenblick E. H., Olivetti G., Meggs L. G., Capasso J. M. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res. 1990 Oct;67(4):871–885. doi: 10.1161/01.res.67.4.871. [DOI] [PubMed] [Google Scholar]
  4. Anversa P., Ricci R., Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol. 1986 May;7(5):1140–1149. doi: 10.1016/s0735-1097(86)80236-4. [DOI] [PubMed] [Google Scholar]
  5. Anversa P., Vitali-Mazza L., Visioli O., Marchetti G. Experimental cardiac hypertrophy: a quantitative ultrastructural study in the compensatory stage. J Mol Cell Cardiol. 1971 Dec;3(3):213–227. doi: 10.1016/0022-2828(71)90042-3. [DOI] [PubMed] [Google Scholar]
  6. Buja L. M., Willerson J. T. Clinicopathologic correlates of acute ischemic heart disease syndromes. Am J Cardiol. 1981 Feb;47(2):343–356. doi: 10.1016/0002-9149(81)90407-0. [DOI] [PubMed] [Google Scholar]
  7. Buja L. M., Willerson J. T. The role of coronary artery lesions in ischemic heart disease: insights from recent clinicopathologic, coronary arteriographic, and experimental studies. Hum Pathol. 1987 May;18(5):451–461. doi: 10.1016/s0046-8177(87)80030-8. [DOI] [PubMed] [Google Scholar]
  8. Capasso J. M., Jeanty M. W., Palackal T., Olivetti G., Anversa P. Ventricular remodeling induced by acute nonocclusive constriction of coronary artery in rats. Am J Physiol. 1989 Dec;257(6 Pt 2):H1983–H1993. doi: 10.1152/ajpheart.1989.257.6.H1983. [DOI] [PubMed] [Google Scholar]
  9. Capasso J. M., Li P., Anversa P. Nonischemic myocardial damage induced by nonocclusive constriction of coronary artery in rats. Am J Physiol. 1991 Mar;260(3 Pt 2):H651–H661. doi: 10.1152/ajpheart.1991.260.3.H651. [DOI] [PubMed] [Google Scholar]
  10. Capasso J. M., Palackal T., Olivetti G., Anversa P. Left ventricular failure induced by long-term hypertension in rats. Circ Res. 1990 May;66(5):1400–1412. doi: 10.1161/01.res.66.5.1400. [DOI] [PubMed] [Google Scholar]
  11. Feild B. J., Russell R. O., Jr, Dowling J. T., Rackley C. E. Regional left ventricular performance in the year following myocardial infarction. Circulation. 1972 Oct;46(4):679–689. doi: 10.1161/01.cir.46.4.679. [DOI] [PubMed] [Google Scholar]
  12. Fletcher P. J., Pfeffer J. M., Pfeffer M. A., Braunwald E. Left ventricular diastolic pressure-volume relations in rats with healed myocardial infarction. Effects on systolic function. Circ Res. 1981 Sep;49(3):618–626. doi: 10.1161/01.res.49.3.618. [DOI] [PubMed] [Google Scholar]
  13. Grossman W., Jones D., McLaurin L. P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975 Jul;56(1):56–64. doi: 10.1172/JCI108079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Harrison D. G., White C. W., Hiratzka L. F., Doty D. B., Barnes D. H., Eastham C. L., Marcus M. L. The value of lesion cross-sectional area determined by quantitative coronary angiography in assessing the physiologic significance of proximal left anterior descending coronary arterial stenoses. Circulation. 1984 Jun;69(6):1111–1119. doi: 10.1161/01.cir.69.6.1111. [DOI] [PubMed] [Google Scholar]
  16. JOHNS T. N. P., OLSON B. J. Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg. 1954 Nov;140(5):675–682. doi: 10.1097/00000658-195411000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LINZBACH A. J. Heart failure from the point of view of quantitative anatomy. Am J Cardiol. 1960 Mar;5:370–382. doi: 10.1016/0002-9149(60)90084-9. [DOI] [PubMed] [Google Scholar]
  18. Loud A. V., Anversa P. Morphometric analysis of biologic processes. Lab Invest. 1984 Mar;50(3):250–261. [PubMed] [Google Scholar]
  19. Maseri A., Chierchia S. Coronary artery spasm: demonstration, definition, diagnosis, and consequences. Prog Cardiovasc Dis. 1982 Nov-Dec;25(3):169–192. doi: 10.1016/0033-0620(82)90015-9. [DOI] [PubMed] [Google Scholar]
  20. McKay R. G., Pfeffer M. A., Pasternak R. C., Markis J. E., Come P. C., Nakao S., Alderman J. D., Ferguson J. J., Safian R. D., Grossman W. Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986 Oct;74(4):693–702. doi: 10.1161/01.cir.74.4.693. [DOI] [PubMed] [Google Scholar]
  21. Oalmann M. C., Palmer R. W., Guzmán M. A., Strong J. P. Sudden death, coronary heart disease, atherosclerosis and myocardial lesions in young men. Am J Epidemiol. 1980 Nov;112(5):639–649. doi: 10.1093/oxfordjournals.aje.a113036. [DOI] [PubMed] [Google Scholar]
  22. Olivetti G., Capasso J. M., Meggs L. G., Sonnenblick E. H., Anversa P. Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res. 1991 Mar;68(3):856–869. doi: 10.1161/01.res.68.3.856. [DOI] [PubMed] [Google Scholar]
  23. Olivetti G., Capasso J. M., Sonnenblick E. H., Anversa P. Side-to-side slippage of myocytes participates in ventricular wall remodeling acutely after myocardial infarction in rats. Circ Res. 1990 Jul;67(1):23–34. doi: 10.1161/01.res.67.1.23. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Pantely G. A., Bristow J. D. Ischemic cardiomyopathy. Prog Cardiovasc Dis. 1984 Sep-Oct;27(2):95–114. doi: 10.1016/0033-0620(84)90021-5. [DOI] [PubMed] [Google Scholar]
  26. Pfeffer J. M., Pfeffer M. A., Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res. 1985 Jul;57(1):84–95. doi: 10.1161/01.res.57.1.84. [DOI] [PubMed] [Google Scholar]
  27. Pfeffer M. A., Lamas G. A., Vaughan D. E., Parisi A. F., Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988 Jul 14;319(2):80–86. doi: 10.1056/NEJM198807143190204. [DOI] [PubMed] [Google Scholar]
  28. Pfeffer M. A., Pfeffer J. M., Fishbein M. C., Fletcher P. J., Spadaro J., Kloner R. A., Braunwald E. Myocardial infarct size and ventricular function in rats. Circ Res. 1979 Apr;44(4):503–512. doi: 10.1161/01.res.44.4.503. [DOI] [PubMed] [Google Scholar]
  29. Pfeffer M. A., Pfeffer J. M., Steinberg C., Finn P. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation. 1985 Aug;72(2):406–412. doi: 10.1161/01.cir.72.2.406. [DOI] [PubMed] [Google Scholar]
  30. Roberts C. S., Roberts W. C. Cross-sectional area of the proximal portions of the three major epicardial coronary arteries in 98 necropsy patients with different coronary events. Relationship to heart weight, age and sex. Circulation. 1980 Nov;62(5):953–959. doi: 10.1161/01.cir.62.5.953. [DOI] [PubMed] [Google Scholar]
  31. Roberts W. C., Jones A. A. Quantitation of coronary arterial narrowing at necropsy in sudden coronary death: analysis of 31 patients and comparison with 25 control subjects. Am J Cardiol. 1979 Jul;44(1):39–45. doi: 10.1016/0002-9149(79)90248-0. [DOI] [PubMed] [Google Scholar]
  32. Roberts W. C. The coronary arteries and left ventricle in clinically isolated angina pectoris: a necropsy analysis. Circulation. 1976 Sep;54(3):388–390. doi: 10.1161/01.cir.54.3.388. [DOI] [PubMed] [Google Scholar]
  33. Roeske W. R., Savage R. M., O'Rourke R. A., Bloor C. M. Clinicopathologic correlations in patients after myocardial infarction. Circulation. 1981 Jan;63(1):36–45. doi: 10.1161/01.cir.63.1.36. [DOI] [PubMed] [Google Scholar]
  34. Ross J., Jr, Sonnenblick E. H., Taylor R. R., Spotnitz H. M., Covell J. W. Diastolic geometry and sarcomere lengths in the chronically dilated canine left ventricle. Circ Res. 1971 Jan;28(1):49–61. doi: 10.1161/01.res.28.1.49. [DOI] [PubMed] [Google Scholar]
  35. Schuster E. H., Bulkley B. H. Ischemic cardiomyopathy: a clinicopathologic study of fourteen patients. Am Heart J. 1980 Oct;100(4):506–512. doi: 10.1016/0002-8703(80)90663-8. [DOI] [PubMed] [Google Scholar]
  36. Taylor G. J., Humphries J. O., Mellits E. D., Pitt B., Schulze R. A., Griffith L. S., Achuff S. C. Predictors of clinical course, coronary anatomy and left ventricular function after recovery from acute myocardial infarction. Circulation. 1980 Nov;62(5):960–970. doi: 10.1161/01.cir.62.5.960. [DOI] [PubMed] [Google Scholar]
  37. Vitali-Mazza L., Anversa P., Tedeschi F., Mastandrea R., Mavilla V., Visioli O. Ultrastructural basis of acute left ventricular failure from severe acute aortic stenosis in the rabbit. J Mol Cell Cardiol. 1972 Dec;4(6):661–671. doi: 10.1016/0022-2828(72)90119-8. [DOI] [PubMed] [Google Scholar]
  38. Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
  39. Warnes C. A., Roberts W. C. Sudden coronary death: relation of amount and distribution of coronary narrowing at necropsy to previous symptoms of myocardial ischemia, left ventricular scarring and heart weight. Am J Cardiol. 1984 Jul 1;54(1):65–73. doi: 10.1016/0002-9149(84)90305-9. [DOI] [PubMed] [Google Scholar]
  40. Warren S. E., Royal H. D., Markis J. E., Grossman W., McKay R. G. Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis. J Am Coll Cardiol. 1988 Jan;11(1):12–19. doi: 10.1016/0735-1097(88)90159-3. [DOI] [PubMed] [Google Scholar]
  41. White C. W., Wright C. B., Doty D. B., Hiratza L. F., Eastham C. L., Harrison D. G., Marcus M. L. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med. 1984 Mar 29;310(13):819–824. doi: 10.1056/NEJM198403293101304. [DOI] [PubMed] [Google Scholar]

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