Effects of ryanodine on ouabain-induced spontaneous mechanical and electrical oscillations in guinea-pig heart.

The effects of ryanodine on ventricular arrhythmias in guinea-pigs in vivo, on delayed after potentials and after contractions, and on spontaneous oscillations of the membrane potential (SOP) and of resting tension (SOT) of guinea-pig papillary muscle under ouabain intoxication were studied. After addition of ouabain (1 microM) the after potentials, after contractions, and SOP and SOT amplitude were significantly increased. The power spectra of SOT and SOP under these conditions had a resonance harmonic with the frequency of about 5 Hz. Three to 5 mins after the addition of ryanodine (0.1-0.5 microM), the after potentials, after contractions, and SOP and SOT were abolished, suggesting a close relationship between these oscillations and the oscillatory activity of sarcoplasmic reticulum. In in vivo experiments, ouabain-induced (75-115 micrograms/kg) ventricular arrhythmias were terminated 4 to 5 min after intravenous injection of ryanodine (15 micrograms/kg); within 8-10 min, sinus rhythm was completely restored. We attribute the antiarrhythmic effect of ryanodine to a cellular effect and alteration of SR function, rather than to effects that are secondary to this.