The influence of molecular form of local anesthetic-type antiarrhythmic agents on reduction of the maximum upstroke velocity of canine cardiac Purkinje fibers.

1 The effects of OPC-88117, a new antiarrhythmic agent, on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2 In papillary muscles, OPC-88117 above 3 x 10-6M caused a dose-dependent prolongation of action potential duration (APD). The curves relating membrane potential and V,,ax were shifted by OPC-88117 to the direction of more negative potentials (9 mV at 10-M).6 In single ventricular myocytes treated with OPC-88117 (1-3 x 1O-4M), the V,,.ax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7 These findings suggest that the primary electrophysiological effect of OPC-88117 on the cardiac muscle cell is prolongation of APD (Class III action) and that at high concentrations, it may also possess a lignocaine-like sodium channel inhibitory effect (Class I action).

Section: Action Potentials Ofpapillary Musclementioning

confidence: 43%

Electrophysiological effects of OPC‐88117, a new antiarrhythmic agent on papillary muscles and single ventricular myocytes isolated from guinea‐pig hearts

Toyama

Kodama

Honjo

et al. 1989

“…Since the entire tissue was excited simultaneously and there was no conduction within the preparation under the present experimental conditions, the decrease in Vmax by Ro 22-9194 or moricizine without any accompanying change in RP reflects an inhibitory effect of these drugs on the fast sodium inward current, INa (Gintant et al, 1983;Grant et al, 1984). The potency of Vmax inhibition by Ro 22-9194 in guinea-pig papillary muscles constantly driven at 1.0 Hz (IC20 = 11 AM) is approximately one tenth of moricizine (IC20 = 1.3 JAM) but is still comparable to those of quinidine, disopyramide or mexiletine (Campbell, 1983).…”

Section: Discussionmentioning

confidence: 83%

Electrophysiological effects of Ro 22–9194, a new antiarrhythmic agent, on guinea‐pig ventricular cells

Maruyama

Kodama

Anno

et al. 1995

“…The characteristics of the use-dependent inhibition of V,,.x induced by pirmenol are similar to those of slow kinetic drugs, such as disopyramide which was shown to have a recovery time constant of 12.0 to 37.8s (Campbell, 1983a;Varro et al, 1985), rather than of fast kinetic drugs, according to the classification proposed by Courtney (1980a). Previous studies indicate that the onset rate of the use-dependent block correlates directly with molecular weight, (Courtney, 1979;1980a,b) and increases with increasing drug concentration (Courtney, 1980a;Gintant et al, 1983;Grant et al, 1984). The studies of 2 ms I I--Onset recovery of Vmax from the block show a strong correlation between molecular weight and recovery times (Courtney, 1980a,b;Grant et al, 1984).…”

Section: Recoveryfrom the Use-dependent Effect Ofpirmenolmentioning

confidence: 80%

Use‐dependent effects of pirmenol on and conduction in guinea‐pig ventricular myocardium

Hasegawa

Hirai

Noguchi

et al. 1990

1 The use-dependent effects of pirmenol, a new antiarrhythmic drug, on the maximal rate of rise (V,) 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 V,,,x 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 1OpM) prolonged the action potential duration, while concentrations greater than 0.1 mm shortened it markedly.3 The resting block of V,,.x in the presence of 10 and 30M 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 30M pirmenol during 0.2, 1, 2 and 3Hz stimulations was dose-and rate-dependent. 5 In the presence of 30Mm pirmenol, mean values of time constants for the onset of the use-dependent inhibition of V,,,x and conduction velocity during a 2Hz stimulation were 1.32 + 0.15 and 1.28 + 0.09s, respectively. The recovery time constants averaged 15.83 + 2.14 (for V,,.x) and 27.80 + 8.74 (for conduction velocity) s in the presence of 30 gM pirmenol.6 These results showed that the characteristics of the use-dependent inhibition of V,,mx and conduction velocity induced by pirmenol are similar to those of slow kinetic drugs such as disopyramide rather than of fast ones.