Electrophysiological and Beta-Receptor Blocking Effects of MJ 1999 on Dog and Rabbit Cardiac Tissue

Effects of MJ 1999 (1 x 10 -9 M to 1 x10 -2 M) on rabbit right atrial and canine Purkinje fiber preparations were studied. MJ 1999 had a pA 2 of 6.1 against the chronotropic effect of isoproterenol on rabbit SA node. Significant slowing first occurred with MJ 1999 at 1 x 10 -4 M. The spontaneous firing rate of Purkinje fibers in vitro did not change significantly after exposure to MJ 1999 1 x 10 -4 M. Idioventricular rate was slowed and idioventricular escape time was prolonged in dogs with atrioventricular block after MJ 1999, 2.0 mg/kg. MJ 1999, 1 x 10 -7 M to 5 x 10 -4 M, had no effect on resting potential, overshoot and amplitude of phase 0 of transmembrane potentials (TMP) recorded from canine ventricular muscle, canine Purkinje fibers or rabbit atrial fibers nor did it affect phase 0 V · max of TMP recorded from the Purkinje or atrial fibers. Similar concentrations of MJ 1999 had no effect on membrane responsiveness in Purkinje fibers. In Purkinje fibers, control action potential duration (APD) was 325 msec and the effective refractory period (ERP) 277 msec. MJ 1999, 1 x 10 -3 M, increased the APD to 470 msec and ERP to 404 msec. In ventricular muscle fibers, APD was 230 msec and the ERP was 223 msec, under control conditions. MJ 1999, 1 x 10 -3 M, increased the APD to 281 msec and ERP to 267 msec. Changes in APD and ERP induced by MJ 1999 were magnified at slower rates of stimulation. The effects of MJ 1999 on both APD and ERP were more marked in Purkinje fibers than in ventricular muscle fibers. The effects of MJ 1999 on phase 0 of the TMP and on repolarization and refractoriness of the TMP differ markedly from those seen with quinidine, procainamide, and lidocaine.