Angiotensin-converting enzyme inhibition and beta-adrenoceptor blockade regress established ventricular remodeling in a canine model of discrete myocardial damage

Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.

OBJECTIVES. This study was designed to assess the effect of angiotensin-converting enzyme inhibition and beta-adrenoreceptor blockade on established ventricular remodeling. BACKGROUND. Angiotensin-converting enzyme inhibitor therapy attenuates the development of ventricular remodeling when given shortly after myocardial infarction. However, regression of established ventricular remodeling after infarction has received little attention. METHODS. The relative effects of angiotensin-converting enzyme inhibitor therapy and beta-adrenoceptor blockade on established ventricular remodeling were assessed in a canine model characterized by increased left ventricular mass and chamber dilation as a result of localized myocardial necrosis produced by transmyocardial direct current shock. Dogs were randomly assigned to 3 months of therapy with captopril (25 mg twice daily, n = 7) or metoprolol (100 mg twice daily, n = 7) or to a control group with no intervention (n = 6), 11 +/- 4 (mean +/- SD) months after acute myocardial damage. RESULTS. Compared with the control group, dogs in both the captopril and metoprolol groups had reduced left ventricular mass as measured by magnetic resonance imaging (-8.1 +/- 3.8 vs. 1.7 +/- 2.8 g, p = 0.003 and -9.6 +/- 5.6 vs. 1.7 +/- 2.8 g, p = 0.001), respectively. Captopril and metoprolol also produced a reduction in left ventricular end-diastolic volume (-7.6 +/- 6.0 and -6.0 +/- 5.8 ml, respectively) compared with the control value (-1.6 +/- 3.8 ml) (p = 0.14 [NS]). Both agents reduced mean arterial pressure but had disparate effects on pulmonary wedge pressure and right atrial pressure. There was no significant correlation between change in ventricular mass or volume and change in any measured hemodynamic or neurohormonal variable. CONCLUSIONS. These data suggest that pharmacologic intervention with angiotensin-converting enzyme inhibition or beta-adrenoceptor blockade can result in regression of established ventricular remodeling. The mechanism of this response will require further study, but these data did not support a close association between regression of remodeling and hemodynamic unloading of the ventricle or systemic neuroendocrine factors.

This article has been cited by other articles:

				S. Gupta, D. Young, and S. Sen Inhibition of NF-{kappa}B induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H20 - H29. [Abstract] [Full Text] [PDF]

				H. N. Sabbah The cardiac support device and the Myosplint: treating heart failure by targeting left ventricular size and shape Ann. Thorac. Surg., June 1, 2003; 75(90060): S13 - 19. [Abstract] [Full Text] [PDF]

				W. F. Saavedra, R. S. Tunin, N. Paolocci, T. Mishima, G. Suzuki, C. W. Emala, P. A. Chaudhry, P. Anagnostopoulos, R. C. Gupta, H. N. Sabbah, et al. Reverse remodeling and enhancedadrenergic reserve from passive externalsupport in experimental dilated heart failure J. Am. Coll. Cardiol., June 19, 2002; 39(12): 2069 - 2076. [Abstract] [Full Text] [PDF]

				R. S. B. Beanlands, C. Nahmias, E. Gordon, G. Coates, R. deKemp, G. Firnau, and E. Fallen The Effects of {beta}1-Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction : A Double-Blind, Placebo-Controlled, Positron-Emission Tomography Study Circulation, October 24, 2000; 102(17): 2070 - 2075. [Abstract] [Full Text] [PDF]

				C. M. Kramer, P. D. Nicol, W. J. Rogers, P. S. Seibel, C. S. Park, and N. Reichek beta -Blockade improves adjacent regional sympathetic innervation during postinfarction remodeling Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1429 - H1434. [Abstract] [Full Text] [PDF]

				D. V. Exner, D. L. Dries, M. A. Waclawiw, B. Shelton, and M. J. Domanski Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the studies of left ventricular dysfunction J. Am. Coll. Cardiol., March 15, 1999; 33(4): 916 - 923. [Abstract] [Full Text] [PDF]

				E. J. Eichhorn and M. R. Bristow Medical Therapy Can Improve the Biological Properties of the Chronically Failing Heart: A New Era in the Treatment of Heart Failure Circulation, November 1, 1996; 94(9): 2285 - 2296. [Abstract] [Full Text]

				J. N. Cohn Structural Basis for Heart Failure : Ventricular Remodeling and Its Pharmacological Inhibition Circulation, May 15, 1995; 91(10): 2504 - 2507. [Full Text]