Electrophysiological effects of 5-hydroxypropafenone on guinea pig ventricular muscle fibers

The effects of 5-hydroxypropafenone (5-OH-P), the main metabolite of propafenone, were studied in guinea pig papillary muscles obtained from untreated animals and from animals pretreated with 5-OH-P, 3 mg/kg for 24 days. In untreated muscles perfused with 2.7 and 5.4 mM K+, 5-OH-P depressed action potential amplitude and Vmax, reduced the resting membrane potential, and prolonged the effective refractory period (ERP), but had no effect on the duration of the action potential (APD), recovery time (RT), or ERP/RT ratio. 5-OH-P also shifted the membrane responsiveness curve downward and to the left (i.e., in hyperpolarizing direction), prolonged the ERP/APD ratio, depressed the amplitude and Vmax, and shortened the duration of the slow action potentials induced by isoproterenol in K+-depolarized muscles. Pretreatment with 5-OH-P had no effect on phase 0 characteristics or resting membrane potential, but it shortened the APD, ERP, and RT and decreased the ERP/APD ratio. Further addition of 5-OH-P produced similar but more marked changes than in untreated muscles. In papillary muscles perfused with 10 mM K+, the depressant effects of 5-OH-P on phase 0 characteristics and ERP/APD ratio were potentiated. A slight lengthening of the APD was also observed. Because all these effects are similar to those previously described with propafenone, it is concluded that 5-OH-P is an active metabolite which exhibits class 1 antiarrhythmic effects and which may be responsible for some of the cardiodepressant and antiarrhythmic effects previously described for propafenone.