Cellular electrophysiology and beta-adrenergic-blocking activity of dilevalol, the R,R-isomer of labetalol, on isolated canine cardiac tissues.

Dilevalol is a beta-adrenergic receptor-blocking drug derived from labetalol. Many beta blockers exert local anesthetic effects or alter repolarization in cardiac tissue. Because the cellular electrophysiologic effects of dilevalol have not been studied, we investigated the actions of dilevalol on canine cardiac tissues using standard microelectrode techniques. We also tested the beta-blocking actions of dilevalol in isolated Purkinje fibers. This was done by measuring the inhibition of the positive chronotropic response to 10(-6) M isoproterenol before and after treatment with the drug. Dilevalol at 10(-9) M produced slight beta blockade, whereas 10(-6) M produced maximal (approximately 90%) effects. In normal Purkinje fibers, dilevalol less than or equal to 10(-6) M did not change the dV/dtmax or action potential duration (APD). Dilevalol at 10(-5) M produced rate-dependent decreases of dV/dtmax, and decreased the plateau amplitude while prolonging total APD of the Purkinje fibers. In ventricular muscle cells, dilevalol greater than or equal to 10(-8) M increases APD, whereas less than or equal to 10(-5) M does not decrease dV/dtmax. Dilevalol less than or equal to 10(-6) M does not decrease automaticity in Purkinje fibers at either the high or the low level of membrane potential. In summary, dilevalol produces significant beta blockade in normal cardiac tissues. The dose-response curve for this action is comparable to that of propranolol. Dilevalol also prolongs APD in ventricular muscle cells. Dilevalol may reduce arrhythmias through either class II or class III effects.