Analysis of antiarrhythmic effect of ryanodine in guinea-pigs

The effects of ryanodine on (1) ventricular arrhythmias in guinea-pigs in vivo, (2) delayed afterpotentials and aftercontractions and (3) spontaneous oscillations of the membrane potential (SOP) and of resting tension (SOT) of guinea-pig papillary muscle under ouabain intoxication have been studied. After addition of ouabain (1 microM), the afterpotentials, aftercontractions and the amplitude of SOP and SOT were significantly increased. The power spectra of SOT and SOP under these conditions had a resonance harmonic with a frequency of about 5 Hz. The afterpotentials, aftercontractions, SOP and SOT were abolished 3 to 5 min after ryanodine addition (0.1 to 0.5 microM), suggesting a close relationship between these oscillations and the oscillatory activity of sarcoplasmic reticulum. During in vivo experiments, ouabain-induced (75 to 115 micrograms/kg) ventricular arrhythmias were terminated 4 to 5 min after the intravenous injection of ryanodine (15 micrograms/kg) and within 8 to 10 min, the sinus rhythm was completely restored. We conclude that the antiarrhythmic effect of ryanodine is related to the inhibition of the diastolic fluctuations of the membrane potential.