Acute effects of amiodarone on action potentials of isolated guinea-pig ventricular muscle exposed to simulated ischemic solution and metabolic inhibitors.

1. Acute effects of an antiarrhythmic agent, amiodarone (AM), on action potentials from isolated guinea-pig ventricular papillary muscles exposed to simulated ischemic solution and Tyrode's solution containing NaCN or dinitrophenol (DNP) were examined. 2. In the papillary muscles exposed to simulated solution (K+ = 6 mM, glucose = 2.3 mM, pH = 7.1, PO2 less than 40 mmHg) or metabolic inhibitors (10(-3) M NaCN or 10(-4) M DNP), resting membrane potential (RMP) and maximum upstroke velocity (Vmax) of action potential were decreased with increasing time to the exposure, and action potential duration (APD) was shortened. In these conditions, addition of 4.4 x 10(-5) M AM produced transient and small increase in the APD and Vmax, followed by progressive APD-shortening and decrease in Vmax and RMP. 3. These results suggest that acute AM's antiarrhythmic effects reported are not due to APD prolonging action (Vaughan Williams Class III) of the drug, but mainly due to its local anesthetic action (Class I).