Electrophysiological effects of sulfinpyrazone on canine cardiac Purkinje fibers

Sulfinpyrazone, administered prophylactically following myocardial infarction, has been reported to reduce the incidence of sudden death. Because direct antiarrhythmic action may, in part, account for this finding, electrophysiological effects of sulfinpyrazone were studied in isolated superfused canine cardiac Purkinje fibers. Using conventional microelectrode recording techniques and programmed electrical stimulation, transmembrane action potential (AP) characteristics and effective refractory period (ERP) were determined in seven experiments under control conditions and during sequential 30-min periods of tissue exposure to 10^-6, 10^-5, and 10^-4 M sulfinpyrazone (pacing cycle lengths 1000 and 500 ms). In six out of seven experiments, recordings were repeated during a 30- to 45-min drug-free recovery period. In four additional experiments, spontaneously depolarizing Purkinje fibers with low resting membrane potentials (-55 to -65 mV) were superfused with 10^-4 M sulfinpyrazone for 45 min following a drug-free control period. AP resting potential, rate of rise of AP phase 0, AP duration, and ERP were not altered significantly from control or recovery values by sulfinpyrazone exposure. Similarly, neither the AP phase 4 slope nor the mean cycle length (678 ± 32 ms vs. control 665 ± 20 ms, N = 4) of spontaneously firing Purkinje fibers was affected by drug. Thus, sulfinpyrazone did not exhibit direct electrophysiological actions comparable to those associated with conventional antiarrhythmic drugs.