Key result
In cardiomyopathic hamsters, combining metoprolol and spironolactone did not improve hemodynamics more than either drug alone but exerted additive effects on cardiac remodeling.
Why the study?
Does the combination of metoprolol and spironolactone improve hemodynamics and cardiac remodeling in dilated cardiomyopathic hamsters?
Does the combination of metoprolol and spironolactone improve hemodynamics and cardiac remodeling in dilated cardiomyopathic hamsters?
In a hamster model of dilated cardiomyopathy, combining metoprolol and spironolactone provides additive benefits on cardiac remodeling compared to either drug alone.
No added hemodynamic benefit from combination in hamster model; leaves open additive remodeling effects for clinical investigation.
The use of beta-blockers reduces angiotensin II levels, but could not adequately suppress aldosterone production. Thus, the combination of a beta-blocker with an aldosterone receptor antagonist could exert additive effects. The effects of metoprolol and spironolactone and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters (CMH) were investigated. The Bio TO-2 dilated strain of CMH was treated orally with metoprolol (10 mg/kg/day), spironolactone (20 mg/kg/day), or both according to a 2 x 2 factorial design (24 animals per group) from 120 days of age and during 120 days. As compared to corresponding untreated groups, metoprolol significantly decreased mean blood pressure (-7%), and metoprolol and spironolactone significantly increased cardiac output (18% and 19%, respectively), mesenteric blood flow (11% and 14%), and femoral blood flow (13% and 17%), and significantly decreased systemic (-24% and -15%), mesenteric (-14% and -13%) and femoral (-19% and -10%) vascular resistances. Metoprolol significantly increased renal blood flow (22%) and significantly decreased renal vascular resistance (-23%). Metoprolol and spironolactone significantly decreased the cavity area of the left ventricle (-21% and -32%, respectively) and the collagen density of the left (-36% and -39%) and right (-38% and -43%) ventricles. Although the combination did not induce stronger effects than each drug alone on the systemic and most regional hemodynamic variables, it did have a stronger effect on the cardiac remodeling (compared to control group: -24%, -34%, and -46% for the left ventricle cavity area, -33%, -35%, and -62% for collagen density in the left ventricle, and -52%, -57%, and -59% for collagen density in the right ventricle, respectively, in the metoprolol, spironolactone, and metoprolol + spironolactone groups). In CMH, metoprolol and spironolactone combined did not improve hemodynamics more than each drug alone, but did exert additive effects on cardiac remodeling.
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Goineau et al. (2002) studied Dilated cardiomyopathy (n=96). Metoprolol and spironolactone combination vs. Untreated control, metoprolol alone, and spironolactone alone was evaluated on Hemodynamics and cardiac remodeling. In cardiomyopathic hamsters, combining metoprolol and spironolactone did not improve hemodynamics more than either drug alone but exerted additive effects on cardiac remodeling.
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