EFFECTS OF CHRONIC BETA-ADRENERGIC-BLOCKADE ON THE LEFT-VENTRICULAR AND CARDIOCYTE ABNORMALITIES OF CHRONIC CANINE MITRAL REGURGITATION

The mechanism by which beta blockade improves left ventricular dysfunc tion in various cardiomyopathies has been ascribed to improved contrac tile function of the myocardium or to improved beta-adrenergic respons iveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develop s in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardiu m. Two groups of six dogs with chronic severe mitral regurgitation wer e studied. After 3 mo both groups had developed similar and significan t left ventricular dysfunction. One group was then gradually beta-bloc ked while the second group continued to be observed without further in tervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractili ty of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. H owever, contractility of cardiocytes isolated from the beta-blocked ve ntricles was virtually normal. Consistent with these data, myofibrilla r density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contra ctile elements to generate force in the beta-blocked group. We conclud e that chronic beta blockade improves left ventricular function in chr onic experimental mitral regurgitation. This improvement was associate d with an improvement in the innate contractile function of isolated c ardiocytes, which in turn is associated with an increase in the number of contractile elements.