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(Circulation. 1995;92:2904-2910.)
© 1995 American Heart Association, Inc.

Articles

Positive and Negative Inotropic Effects of DL-Sotalol and D-Sotalol in Failing and Nonfailing Human Myocardium Under Physiological Experimental Conditions

Christian Holubarsch, MD; Ralf Schneider, MD; Burkert Pieske, MD; Thorsten Ruf, MD; Gerd Hasenfuss, MD; Gustav Fraedrich, MD; Herbert Posival, MD; Hanjörg Just, MD

From the Department of Cardiology and Angiology (C.H., R.S., B.P., T.R., G.H., H.J.), Internal Medicine, University of Freiburg; the Department of Cardiovascular Surgery (G.F.), University of Freiburg, Chirurgische Universitätsklinik; and the Center of Thoraxic- and Cardiovascular Surgery (H.P.), Cardiac Transplantation Center NRW, Germany.

Background DL-Sotalol has class III antiarrhythmic activity through prolongation of the repolarization phase of the action potential as well as ß-adrenoceptor–blocking properties. Although the former effect was found to exert positive inotropic effects in animal experimental studies, the latter may be detrimental in heart failure due to negative inotropism. In contrast to DL-sotalol, D-sotalol is suggested to exert only positive inotropic effects, which were never tested in isolated human myocardium.

Methods and Results Therefore, we investigated the effects of racemic DL-sotalol and its enantiomer D-sotalol in human right atrial muscle strip preparations and in left ventricular muscle strip preparations from nonfailing and end-stage failing human hearts. DL-sotalol and D-sotalol significantly (P<.01) increased peak developed force in atrial preparations by 14.0±3.4% and 16.7±3.8%, respectively, but had no effect in ventricular myocardium. In nonfailing ventricular myocardium, both DL-sotalol and D-sotalol shifted the dose-response curve for isoproterenol to higher concentrations (P<.01); however, DL-sotalol was 100-fold more effective than D-sotalol. In nonfailing myocardium, a positive force-frequency relation was found between 30 and 120 beats per minute, but isoproterenol was much more powerful in its inotropic effects. In failing myocardium, reduction in stimulation rate from 120 to 30 beats per minute increased peak developed force more pronounced than did the application of isoproterenol.

Conclusions (1) D-Sotalol has no relevant ß-adrenoceptor–blocking activity compared with DL-sotalol. (2) Neither DL-sotalol nor D-sotalol exhibit positive inotropic effects in human left ventricular myocardium. (3) Heart rate reduction increases contractile force in end-stage failing human myocardium due to an inverse force-frequency relation and thereby counteracts the potential negative inotropic properties of ß-blockade.

Key Words: receptors • adrenergic • beta • myocardium • sotalol

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