Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine Purkinje fibres.

The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1-30 mumol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 mumol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 mumol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 +/- 5.2 ms (control, n = 6) to 217.1 +/- 17.8 ms (n = 6, P less than 0.05). In the presence of restacorin (10 mumol/l), a second slow component for recovery of maximal action potential upstroke rising velocity was expressed having a time constants of 8.5 +/- 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P less than 0.01) by 10 mumol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.