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The effects of ellagic acid, a phenolic phytochemical contained in fruits and vegetables, on sarcoplasmic reticulum Ca 2+ uptake and myocardial contraction were examined in mouse ventricular myocardia. In cardiomyocytes loaded with Fura-2 (a fluorescent Ca 2+ indicator), isoprenaline (a -adrenoceptor agonist) produced a decrease in the basal fluorescence ratio. This decrease was inhibited by propranolol (a -adrenoceptor antagonist) and cyclopiazonic acid (a sarcoplasmic reticulum Ca 2+-ATPase inhibitor). Ellagic acid produced a decrease in basal fluorescence ratio, which was completely inhibited by cyclopiazonic acid. In isolated myocardial tissue preparations, isoprenaline increased the contractile force and shortened the time required for relaxation. Ouabin, a cardiac glycoside, increased the contractile force but did not affect the time required for relaxation. Ellagic acid shortened the time required for relaxation but did not affect the contractile force. The beating rate of isolated right atria was increased by isoprenaline, but ellagic acid had no effect. In conclusion, ellagic acid accelerates sarcoplasmic reticulum Ca 2+ uptake and myocardial relaxation without affecting the contractile force or the beating rate. Ellagic acid, which has such non-conventional mode of action, may be of value in the long-term maintenance of cardiac function.

The effect of blocking the persistent component of the sodium channel current (late I Na ) on the automatic activity of the isolated guinea pig pulmonary vein myocardium was examined. NCC-3902 blocked late I Na , but did not affect other major ion channel currents stably expressed in cell lines. In isolated pulmonary vein cardiomyocytes, NCC-3902 blocked the late I Na induced by a ramp depolarizing voltage clamp pulse similar to that of the pacemaker depolarization observed in the pulmonary vein myocardium. In isolated pulmonary vein tissue, NCC-3902 decreased the frequency of automatic firing of the myocardium through a reduction of the pacemaker depolarization slope. In isolated pulmonary vein cardiomyocytes, NCC-3902 significantly reduced the firing frequency of Ca 2 transients, but had no effect on Ca 2 sparks. NCC-3902 affected neither the spontaneous beating rate of the right atrium nor the contractile force of the ventricular myocardium. Selective blockers of late I Na like NCC-3902, which inhibit the automatic activity of the pulmonary vein myocardium, appear to be promising as drugs for the pharmacological treatment of atrial fibrillation.

The negative inotropic effects of nine Vaughan Williams class I antiarrhythmic drugs were examined in guinea pig ventricular tissue preparations. The drugs decreased the contractile force of papillary muscles with different potencies: the potency order was propafenone > aprindine > cibenzoline > flecainide > ranolazine > disopyramide > pilsicainide > mexiletine > GS-458967. The potency of drugs correlated with the reported IC 50 values to block the L-type Ca 2 channel rather than the Na channel. The effects of drugs were roughly the same when examined under a high extracellular K solution, which inactivates the Na channel. Furthermore, the attenuation of the extracellular Ca 2 -induced positive inotropy was strong with propafenone, moderate with cibenzoline, and weak with pilsicainide. These results indicate that the negative inotropic effects of class I antiarrhythmic drugs can be largely explained by their blockade of the L-type Ca 2 channel.