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Ventricular remodeling: insights from pharmacologic interventions with angiotensin-converting enzyme inhibitors

  • Sidney Goldstein
  • Victor G. Sharov
  • Jane M. Cook
  • Hani N. Sabbah
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 14)

Abstract

Structural remodeling of the left ventricular (LV) myocardium develops in a time-dependent fashion following acute myocardial infarction and may be an integral component in the transition toward overt heart failure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular level, the remodeling process is associated with myocyte slippage, hypertrophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monotherapy with the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the progression of LV remodeling in dogs with LV dysfunction (ejection fractions 30-40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with enalapril (n = 7) or to no treatment (n = 7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and chamber sphericity increased significantly during the 3 months follow-up period. In contrast, in dogs treated with enalapril ESVI, EDVI and chamber sphericity remained essentially unchanged. Treatment with enalapril attenuated myocyte hypertrophy and the accumulation of interstitial collagen in comparison to untreated dogs. These data indicate that early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibition of direct action of angiotensin-II and possibly the decrease in bradykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling. (Mol Cell Biochem 147: 51–55, 1995)

Key words

ventricular enlargement myocyte hypertrophy interstitial fibrosis angiotensin converting enzyme inhibitors 

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References

  1. 1.
    Sabbah HN, Goldstein S: Ventricular remodeling: consequences and therapy. Europ Heart J 14: 24–29, 1993CrossRefGoogle Scholar
  2. 2.
    Sabbah HN, Stein PD, Kono T, Gheorghiade M, Levine TB, Jafri S, Hawkins ET, Goldstein S: A canine model of chronic heart failure produced by multiple sequential coronary microembolizations. Am J Physiol 260: H1379–H1384, 1991PubMedGoogle Scholar
  3. 3.
    Sabbah HN, Hansen-Smith F, Sharov VG, Kono T, Lesch M, Gengo PG, Steffen RP, Levine TB, Goldstein S: Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure. Circulation 87: 1729–1737, 1993PubMedCrossRefGoogle Scholar
  4. 4.
    Sabbah HN, Shimoyama H, Kono T, Gupta RC, Sharov VG, Scicli G, Levine TB, Goldstein S: Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. Circulation 84: 2852–2859, 1994CrossRefGoogle Scholar
  5. 5.
    Dodge HT, Sandler H, Baxley WA, Hawley RR: Usefulness and limitations of radiographic methods for determining left ventricular volume. Am J Cardiol 18: 10–24, 1966PubMedCrossRefGoogle Scholar
  6. 6.
    Sabbah HN, Kono T, Stein PD, Mancini GBJ, Goldstein S: Left ventricular shape changes during the course of evolving heart failure. Am J Physiol 263: H266–H270, 1992PubMedGoogle Scholar
  7. 7.
    Sabbah HN, Kono T, Stein PD, Mancini GBJ, Goldstein S:The SOLVD Investigators: Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327: 685–691, 1992CrossRefGoogle Scholar
  8. 8.
    Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E: Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 319: 80–86, 1988PubMedCrossRefGoogle Scholar
  9. 9.
    Konstam MA, Rousseau MF, Kronenberg, MW, Udelson JE, Melin J, Stewart D, Dolan N, Edens TR, Ahn S, Kinan D, Howe DM, Kilcoyne L, Metherall J, Benedict C, Yusuf S, Pouleur H: Effects of the angiotensin converting enzyme inhibitor enalapril on long-term progression of left ventricular dysfunction in patients with heart failure. Circulation 86: 431–438, 1992PubMedCrossRefGoogle Scholar
  10. 10.
    Mitchell GF, Lamas GA, Vaughan DE, Pfeffer MA: Left ventricular remodeling in the year after first anterior myocardial infarction: a quantitative analysis of contractile segment lengths and ventricular shape. J Am Coll Cardiol 19: 1136–1144, 1992PubMedCrossRefGoogle Scholar
  11. 11.
    Waagstein F, Caidahl K, Wallentin I, Bergh C-H, Hjalmarson A: Longterm beta-blockade in dilated cardiomyopathy. Effects of short and long-term metoprolol treatment followed by withdrawal and readministration of metoprolol. Circulation 80: 551–563, 1989PubMedCrossRefGoogle Scholar
  12. 12.
    Bonaduce D, Petretta M, Arrichiello P, Conforti G, Montemurro MV, Attisano T, Bianchi V, Morgano G: Effects of captopril treatment on left ventricular remodeling after anterior myocardial infarction: comparison with digitalis. J Am Coll Cardiol 19: 858–863, 1992PubMedCrossRefGoogle Scholar
  13. 13.
    Pfeffer JM, Pfeffer MA, Mirsky I, Braunweld E: Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci 79: 3310–3314, 1982PubMedCrossRefGoogle Scholar
  14. 14.
    Jalil E, Janicki JS, Pick R, Weber KT: Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension: response to captopril. Am J Hypertens 4: 51–55, 1991PubMedGoogle Scholar
  15. 15.
    Mukherjee D, Sen S: Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats. Circ Res 67: 1474–1480, 1990PubMedCrossRefGoogle Scholar
  16. 16.
    Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM: Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res 72: 1245–1254, 1993PubMedCrossRefGoogle Scholar
  17. 17.
    Eghbali M, Czaja MJ, Zeydel M, Weiner FR, Seifter S, Blumenfield OO: Collagen mRNAs in isolated adult heart cells. J Mol Cell Cardiol 20: 267–276, 1988PubMedCrossRefGoogle Scholar
  18. 18.
    Medugorac I, Jacob R: Characterization of left ventricular collagen in the rat. Cardiovasc Res 17: 15–21, 1983PubMedCrossRefGoogle Scholar
  19. 19.
    Dzau VJ: Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 77: I-4–1–13, 1988CrossRefGoogle Scholar
  20. 20.
    Khairallah PA, Robertson AL, Davila D: Effect of angiotensin-II on DNA, RNA and protein synthesis. In: J Genest, R. Koiw (eds) Hypertension. Springer-Verlag, New York, 1972, pp 212–220Google Scholar
  21. 21.
    Ganten D, Schelling P, Flugel RM, Ganten U: Effect of angiotensin and an angiotensin antagonist on iso-renin and cell growth in 3T3 mouse cells. Int Res Commun Med Sci 3: 327–332, 1975Google Scholar
  22. 22.
    Linz W, Henning R, Scholkens BA: Role of the angiotensin II receptor antagonism and converting enzyme inhibition in the progression and regression of cardiac hypertrophy in rats. J Hypertension 8:L S400–S401, 1991Google Scholar
  23. 23.
    Wiemer G, Scholkens BA, Becker RHA, Busse R: Ramilprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 18: 558–563, 1991PubMedCrossRefGoogle Scholar
  24. 24.
    Garg UC, Hassid A: Nitric oxide-generating vasodilators and 8-bromocyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 83: 1774–1777, 1989PubMedCrossRefGoogle Scholar
  25. 25.
    Linz W, Scholkens BA: A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 105: 771–772, 1992PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1995

Authors and Affiliations

  • Sidney Goldstein
    • 1
  • Victor G. Sharov
    • 2
  • Jane M. Cook
    • 2
  • Hani N. Sabbah
    • 2
  1. 1.Henry Ford Hospital2799 West Grand BoulevardDetroitUSA
  2. 2.Department of Medicine, Division of Cardiovascular MedicineHenry Ford Heart and Vascular InstituteDetroitUSA

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