(Circulation. 2000;101:653.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Bradycardia and the Role of ß-Blockade in the Amelioration of Left Ventricular Dysfunction
From the Department of Medicine, Cardiology Division, and the Gazes Cardiac Research Institute, Medical University of South Carolina (M.N., F.G.S., M.K., H.T., G.D.F., G.C., B.A.C.), and the Ralph H. Johnson Department of Veterans Affairs (G.C., B.A.C.), Charleston, SC.
Correspondence to Blase A. Carabello, MD, Chief, Medical Service (111), Veterans Affairs Medical Center, 2002 Holcombe Blvd, Houston, TX 77030.
Background—It is clear that ß-blockers are effective for treatment of congestive heart failure, but their mechanism of action remains controversial. Hypothesized mechanisms include normalization of ß-receptor function and myocardial protection from the effects of catecholamines, possibly by the institution of bradycardia. We hypothesized that ß-blockade–induced bradycardia was an important mechanism by which these agents were effective for correction of LV dysfunction.
Methods and Results—In 2 groups of dogs with mitral regurgitation and LV dysfunction, ß-blockers were instituted. In 1 group that received ß-blockers and pacing (group ß+P), a pacemaker prevented the natural bradycardia that ß-blockers cause. In both groups, substantial LV dysfunction developed. Before ß-blockade, the end-systolic stiffness constant decreased from 3.5±0.1 to 2.7±0.2 (P<0.01) at 3 months in group ß+P. A similar reduction occurred in the group that eventually received only ß-blockers (group ßB). In group ßB, end-systolic stiffness improved after 3 months of ß-blockade from 2.9±0.2 to 3.5±0.4 and was not different from baseline. However, in group ß+P, end-systolic stiffness failed to improve (2.7±0.2) after 3 months of mitral regurgitation, and was 2.9±0.2 at the end of the studies. The contractile function of cardiocytes isolated from the ventricles at the end of the studies confirmed these in vivo estimates of contractility.
Conclusions—We conclude that institution of bradycardia is a major mechanism by which ß-blockers are effective for restoration of contractile function in a model of LV dysfunction.
Key Words: contractility • heart failure • receptors, adrenergic, beta
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