RESUMEN
BACKGROUND: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mM) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS: Both drugs increased contractility of trabecular muscle preparations, while, in Purkinje strands, vesnarinone failed to increase developed force during continuous pacing at 2 Hz. Vesnarinone lengthened APD in both preparations; although this effect was more marked in Purkinje strands. Ventricular muscle APD was not affected by amrinone (1 µM to 1 mM), while, in Purkinje strands, amrinone produced a biphasic effect on APD. Low concentrations (1-100 µM) of amrinone shortened Purkinje fiber APD, while only the highest concentration (1 mM) used lengthened APD. In addition, in Purkinje strand preparations the effects of vesnarinone (10 µM) on APD and developed force were proportional to pacing cycle length at frequencies slower than 2 Hz; however, at frequencies faster than 2 Hz vesnarinone decreased developed force while APD was lengthened. In ventricular trabecular muscle preparations, the effects of vesnarinone were not affected by frequency. CONCLUSIONS: These results indicate clear differences between the effects of vesnarinone and amrinone in isolated cardiac preparations. These differences in experimental effects in isolated cardiac preparations may help provide an explanation for the disappointing clinical response of patients in heart failure to amrinone, while vesnarinone has appeared to be beneficial.
RESUMEN
BACKGROUND: The racemate of sotalol (dl-sotalol) and its dextrorotatory isomer (d-sotalol) are equally effective in increasing isolated cardiac action potential durations. dl-Sotalol, however, is reported to be more effective than d-sotalol in increasing ventricular effective refractoriness following coronary artery occlusion. These differences are attributed to the beta-adrenergic blocking properties of dl-sotalol. We wished to determine if in isolated human ventricular muscle preparations the effects of 30 µM d0 and dl-sotalol could be modified by preexposure to 1 µM isoproterenol. METHODS AND RESULTS: Microelectrodes were used to record action potential duration (APD) in the presence and absence of isoproterenol during continuous pacing. Preparations were obtained from explanted hears of transplant recipients suffering idiopathic cardiomyopathies. Without isoproterenol, APD measured at 90% of repolarization (APD(90)) was significantly increased by both d- and dl-sotalol (352.0 +/- 17.7 to 418.0 +/- 23.8 ms, P <.05; and 339.2 +/- 17.0 to 405.0 +/- 25.3 ms, P <.05; respectively). Isoproterenol alone, prior to sotalol exposure, tended to shorten APD(90) in the two groups first exposed to this beta-adenoceptor agonist and subsequently exposed to either d-sotalol or dl-sotalol (317.5 +/- 16.5 to 286.3 +/- 28.8 ms and 288.0 +/- 16.2 to 254.0 +/- 15.0 ms, respectively). dl-Sotalol significantly increased APD(90) from its baseline value after isoproterenol (288.0 +/- 16.2 to 359.0 +/- 25.1 ms, P <.005) while d-sotalol did not (317.5 +/- 16.5 to 316.2 +/- 28.5 ms, NS). CONCLUSIONS: The beta-adrenergic blocking properties of dl-sotalol may be important in determining antiarrhythmic efficacy when tonic sympathetic nervous activity is high.