USE-DEPENDENT EFFECTS OF PIRMENOL ON VMAX AND CONDUCTION IN GUINEA-PIG VENTRICULAR MYOCARDIUM

1. The use-dependent effects of pirmenol, a new antiarrhythmic drug, on the maximal rate of rise (V̇(max)) of the action potential, conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential characteristics of the muscles. 2. Pirmenol decreased V̇(max) and the overshoot of action potentials in a dose-dependent fashion. Also, doses of pirmenol greater than 1 mM abolished the generation of action potentials. Low concentrations of pirmenol (3 and 10 μM) prolonged the action potential duration, while concentrations greater than 0.1 mM shortened it markedly. 3. The resting block of V̇(max) in the presence of 10 and 30 μM pirmenol was 9.48 ± 3.12 and 20.36 ± 3.61%, and that of conduction velocity 2.87 ± 1.52 and 6.58 ± 2.09%, respectively. 4. The degree of use-dependent block induced by 10 and 30 μM pirmenol during 0.2, 1, 2 and 3 Hz stimulations was dose- and rate-dependent. 5. In the presence of 30 μM pirmenol, mean values of time constants for the onset of the use-dependent inhibition of V̇(max) and conduction velocity during a 2 Hz stimulation were 1.32 ± 0.15 and 1.28 ± 0.09 s, respectively. The recovery time constants averaged 15.83 ± 2.14 (for V̇(max)) and 27.80 ± 8.74 (for conduction velocity) s in the presence of 30 μM pirmenol. 6 These results showed that the characteristics of the use-dependent inhibition of V̇(max) and conduction velocity induced by pirmenol are similar to those of slow kinetic drugs such as disopyramide rather than of fast ones.