Effects of chronic β-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation

Hiroyuki Tsutsui, Francis G. Spinale, Masayoshi Nagatsu, Phillip G. Schmid, Kazuaki Ishihara, Gilberto DeFreyte, George Cooper IV, Blase A. Carabello

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154 Citations (Scopus)

Abstract

The mechanism by which β blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved β-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic β blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually β-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic β blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of β receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the β-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55±4% in the β-blocked group vs. 39±2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the β-blocked group. We conclude that chronic β blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements.

Original languageEnglish
Pages (from-to)2639-2648
Number of pages10
JournalJournal of Clinical Investigation
Volume93
Issue number6
DOIs
Publication statusPublished - Jun 1994

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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