ACTION-POTENTIAL DURATION AND CONTRACTILITY IN CANINE CARDIAC TISSUES- ACTION OF INOTROPIC DRUGS

1. Inotropic and electrophysiologic effects of veratrine, vesnarinone, d-sotalol and tetraethylammonium (TEA) were compared. Action potentia l duration (APD) and contractility were measured in isolated canine Pu rkinje fiber and ventricular trabecular muscle preparations by using s tandard microelectrode techniques. Each drug significantly increased A PD and force development in either tissue. 2. Drug-induced increases i n force development were normalized to increases in APD. The order of efficacy was found to be vesnarinone>veratrine>TEA in ventricular myoc ardium, whereas it was veratrine>>vesnarinone=d-sotalol=TEA in Purkinj e fibers. 3. The force-APD relation was linear for all drugs in the co ncentrations used.4. Simultaneous measurements of APD, force developme nt and intracellular sodium ion activity (a(Na)(i)) in the presence of either veratrine or lidocaine indicated a linear relation between for ce development and changes in a(Na)(i). 5. The relation between APD an d force development was different in ventricular and Purkinje fiber pr eparations. Differences in the veratrine sensitivity of the force-APD relation observed between Purkinje and ventricular preparations sugges t that a(Na)(i)-dependent changes in Na+/Ca2+ exchange may play a more important role in regulation of force generation in Purkinje fibers t han in ventricular myocardium. GEN PHARMAC 31;3:415-418, 1998. (C) 199 8 Elsevier Science Inc.