Author + information
- Received December 20, 1993
- Revision received July 7, 1994
- Accepted July 13, 1994
- Published online December 1, 1994.
- Kenneth M. McDonald, MD, MRCPI∗,
- Thomas Rector, PhD,
- Peter F. Carlyle, BS,
- Gary S. Francis, MD, FACC and
- Jay N. Cohn, MD, FACC
- ↵∗Address for correspondence: Dr. Kenneth M. McDonald, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware Street SE, Minneapolis, Minnesota 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 betaadrenoceptor 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 study was supported by Program Project Grant PO132427 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and a grant from Bristol Myers Squibb Pharmaceutical Company, Princeton, New Jersey.
- Received December 20, 1993.
- Revision received July 7, 1994.
- Accepted July 13, 1994.