POSITIVE AND NEGATIVE INOTROPIC EFFECTS OF DL-SOTALOL AND D-SOTALOL IN FAILING AND NONFAILING HUMAN MYOCARDIUM UNDER PHYSIOLOGICAL EXPERIMENTAL CONDITIONS

Background DL-Sotalol has class III antiarrhythmic activity through pr olongation of the repolarization phase of the action potential as well as beta-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 negativ e inotropism. In contrast to DL-sotalol, D-sotalol is suggested to exe rt only positive inotropic effects, which were never tested in isolate d human myocardium. Methods and Results Therefore, we investigated the effects of racemic DL-sotalol and its enantiomer D-sotalol in human r ight atrial muscle strip preparations and in left ventricular muscle s trip preparations from nonfailing and end-stage failing human hearts. Dt-sotalol and D-sotalol significantly (P<.01) increased peak develope d force in atrial preparations by 14.0+/-3.4% and 16.7+/-3.8%, respect ively, but had no effect in ventricular myocardium. In nonfailing vent ricular myocardium, both DL-sotalol and D-sotalol shifted the dose-res ponse curve for isoproterenol to higher concentrations (P<.01); howeve r 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 m ore pronounced than did the application of isoproterenol. Conclusions (1) D-Sotalol has no relevant beta-adrenoceptor-blocking activity comp ared with DL-sotalol. (2) Neither DL-sotalol nor D-sotalol exhibit pos itive inotropic effects in human Left ventricular myocardium. (3) Hear t rate reduction increases contractile force in end-stage failing huma n myocardium due to an inverse force-frequency relation and thereby co unteracts the potential negative inotropic properties of beta-blockade .