Inotropic and electrophysiological effects of PY 108-068 on isolated cardiac preparations

The inotropic and electrophysiological effects of PY 108-068 (PY), a new Ca-antagonist agent, were studied on isolated atria and guinea-pig papillary muscles. On isolated atria PY produced a dose-dependent decrease in amplitude and rate of spontaneous contractions. This negative inotropic effect was more evident at fast stimulation rates. PY decreased the maximum inotropic and chronotropic responses to isoprenaline and caused a dose-response parallel shift of the Ca dose-response curve. On papillary muscles, PY produced a shortening in action potential duration without changes in the resting potential and the Vmax and amplitude of phase O. PY also produced a dose-dependent decrease in amplitude and Vmax and a shortening of the duration of the slow action potentials elicited by isoprenaline in K (27 mM)-depolarized papillary muscles. These results suggest that in isolated right atria and guinea-pig papillary muscles PY produced a selective inhibition of Ca Influx via the slow inward current.