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

Abstract

The mechanism by which ft blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved ,8-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic 13 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 graduallyfl-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 ,f blockade, contractile function improved substantially.The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of1f receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the ,8-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55±4% in the f-blocked group vs. 39±2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the f-blocked group.We conclude that chronic ft 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. (J. Clin. Invest. 1994. 93:2639-2648.) Key words: mitral valve insufficiency * adrenergic fi receptor blockaders * ventricular function * left heart failure * congestive hypertrophy

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With β-Blockade in Patients With Heart Failure

“…␤-Blockade improves LVEF by biologically augmenting myocyte and chamber contractility. [1][2][3][4] This improvement does not occur immediately but rather between 1 and 3 months of therapy. 3 A partial explanation of biological improvement in LVEF may be upregulation of sarcoplasmic reticulum calcium ATPase (SERCA2), a protein that controls calcium sequestration, and an increase in the relative amount of ␣-myosin heavy chain.…”

“…[1][2][3][4] This results in improved ventricular function, an increase in myocardial chamber efficiency, and a reversal in the pathological remodeling process. [1][2][3][4] In many cases, this translates into a survival benefit, [5][6][7][8] but in the BEST study, there was no clear survival benefit, despite an improvement in left ventricular ejection fraction (LVEF) with bucindolol. 9 However, not all patients have improved LVEF with ␤-blocker therapy.…”

Pathologic Manifestations on Surgical Biopsy and Their Correlation with Clinical Indices in Dogs with Degenerative Mitral Valve Disease

“…Myocardial systolic or diastolic dysfunction accrues from histopathologic changes that cause myocardial decompensation, which in turn induces clinical signs such as cough, dyspnea, and exercise intolerance 3, 4, 8, 9, 10. However, knowledge is incomplete regarding the pathologic progression of myocardial degeneration and attendant difficulties in evaluating myocardial dysfunction in DMVD.…”

“…Because the clinical signs of DMVD develop slowly over a period of years, they are often recognized only after cardiac remodeling has already occurred 19. Several studies in dogs with experimentally induced mitral valve insufficiency showed severe myocardial degeneration (e.g., myofibrillar loss, increased perinuclear space, and hypertrophy) in the LV as early as 4 months after induction of mild mitral regurgitation 10, 20, 21. Similarly, apoptosis of cardiac myocytes was detected before ventricular hemodynamic impairment or systolic dysfunction in experimental dogs with ventricular pacing 22.…”

“…These microenvironmental changes worsen myocardial function by inducing pathologic degeneration characterized by loss of myofibrils, myocardial necrosis, and severe deposition of interstitial connective tissue 6, 8, 9, 10, 11. Also, cardiogenic pulmonary congestion, a result of backward failure, causes pulmonary pathologic changes, such as thickened alveolar septa, the presence of heart failure cells, and hyperplasia of type II pneumocytes 12, 13.…”