Bradycardia and the role of beta-blockade in the amelioration of left ventricular dysfunction

It is clear that beta-blockers are effective for treatment of congestive heart failure, but their mechanism of action remains controversial. Hypothesized mechanisms include normalization of beta-receptor function and myocardial protection from the effects of catecholamines, possibly by the institution of bradycardia. We hypothesized that beta-blockade-induced bradycardia was an important mechanism by which these agents were effective for correction of LV dysfunction.

In 2 groups of dogs with mitral regurgitation and LV dysfunction, beta-blockers were instituted. In 1 group that received beta-blockers and pacing (group beta+P), a pacemaker prevented the natural bradycardia that beta-blockers cause. In both groups, substantial LV dysfunction developed. Before beta-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 beta+P. A similar reduction occurred in the group that eventually received only beta-blockers (group betaB). In group betaB, end-systolic stiffness improved after 3 months of beta-blockade from 2.9+/-0.2 to 3.5+/-0.4 and was not different from baseline. However, in group beta+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.

We conclude that institution of bradycardia is a major mechanism by which beta-blockers are effective for restoration of contractile function in a model of LV dysfunction.