Effects of changrolin on contractility and excitability of isolated cat papillary muscle

Changrolin is a new anti-arrhythmic drug. Its effects on the contractility and excitability as well as its interaction with nicotinamide or CaCl2 were studied on isolated cat papillary muscles driven by electrical stimuli. The cumulative concentration of changrolin 3,6 and 12μg/ml decreased the amplitude of contractions of papillary muscle by 21±10, 38±11 and 51±11%, respectively. This negative inotropic effect was completely antagonized by nicotinamide (4.8 mg/ml) and isoproterenol (0.2μg/ml). The combination of changrolin and CaCl2 produced intermittent or even complete cessations of papillary muscle contractions which were restored by increasing the intensity of stimulation(V). Changrolin 6μg/ml caused the intensity-duration curve shifting upward, and CaCl2 or nicotinamide enhanced this effect. It was suggested that nicotinamide or CaCl2 potentiated the inhibitory effect of changrolin on excitability of papillary muscle.