EXPERIMENTAL STUDIES
Effect of carvedilol in comparison with metoprolol on myocardial collagen postinfarction
Shan Wei, PhD*,
Louis T. C. Chow, FRCPath and
John E. Sanderson, MD, FRCP, FACC*
* Division of Cardiology, Department of Medicine and Therapeutics, Hong Kong SAR, China
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
Manuscript received March 8, 1999;
revised manuscript received December 30, 1999,
accepted February 28, 2000.
Reprint requests and correspondence: Professor J. E. Sanderson, MD, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, 9/F Clinical Sciences Bldg, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
jesanderson{at}cuhk.edu.hk
OBJECTIVES
We sought to compare the effects of two different beta-blockers, carvedilol and metoprolol, to an angiotensin-converting enzyme (ACE) inhibitor (captopril) on myocardial collagen deposition during healing and ventricular remodeling after myocardial infarction (MI).
BACKGROUND
Beta-adrenergic blockade has been shown to be beneficial post-MI and in chronic heart failure. Carvedilol is a new-generation vasodilating beta-blocker with additional alpha1-adrenoceptor antagonism and an antiproliferative action, but it is not known if it is more beneficial than standard selective beta-blockers.
METHODS
Using a rat model of MI, induced by left coronary ligation, we studied the effects of 11 weeks of therapy with oral carvedilol, metoprolol or captopril on hemodynamics, tissue weights, collagen volume fraction and hydroxyproline content.
RESULTS
Both beta-blockers caused similar decreases in heart rate and LVEDP compared with untreated post-MI rats. At equivalent beta-adrenoceptor blocking doses, however, carvedilol, but not metoprolol, attenuated the increase in collagen content in noninfarcted regions and prevented the increase in right ventricular weight/body weight (all p < 0.05), and its effect was similar to captopril. Metoprolol treatment tended to increase right ventricular weight and heart weight (p < 0.05). There were no differences in infarct size between the groups.
CONCLUSIONS
Long-term treatment with both beta-blockers, as well as an ACE inhibitor, benefited the healing process in rats post-MI. At equivalent myocardial beta-adrenoceptor blocking doses, however, carvedilol significantly reduced myocardial collagen in the noninfarcted myocardium and cardiac hypertrophy in the right ventricle, whereas metoprolol had no effect on myocardial collagen deposition.
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Abbreviations and Acronyms
| | CVF | = collagen volume fraction | | DMSO | = dimethy sulphoxide | | IA | = infarcted area | | LV | = left ventricular | | LVEDP | = left ventricular end-diastolic pressure | | MAP | = mean arterial pressure | | MI | = myocardial infarction | | NIA | = noninfarcted area | | RV | = right ventricular |
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