Tokumasa Tsukada

Antiarrhythmic effects of bupuranolol against canine ventricular arrhythmias induced by halothane-adrenaline or two-stage coronary ligation.

Summary We compared the β-adrenoceptor blocking actions of bupuranolol and propranolol using the response to isoprenaline of the strength of contraction of the canine blood-perfused ventricular muscle, of the rate and strength of contraction of the isolated guinea pig heart and of a guinea pig tracheal ring preparation. The potency ratios of bupuranolol to propranolol were 3.6, 3.0, 3.4, and 2.4, respectively. Bupuranolol decreased the maximum dV/dt of the canine ventricular action potential and had no sympathomimetic action. Bupuranolol effectively suppressed halothane-adrenaline ventricular arrhythmias in the dog, reflecting its potency as a β-adrenoceptor antagonist. In contrast, bupuranolol did not suppress ventricular arrhythmias induced by two-stage coronary ligation in the dog. Compared to propranolol and certain other antiarrhythmic drugs, bupuranolol had weaker effects on prolonging the effective refractory period than on the maximum dV/dt of canine ventricular muscle. This suggests that lengthening of the refractory period may be important for suppressing the two-stage coronary ligation arrhythmia and that the mechanism of this arrhythmia might be reentry.

Effects of Nicorandil on the Conductive Coronary Artery of the Dog

The effects of nicorandil (2-nicotinamidoethyl nitrate, SG-75) on the conductive coronary artery were studied and compared with the effects of nitroglycerin and nifedipine. In isolated perfused canine heart preparations with a support dog, nicorandil produced a decrease in the resistance of the conductive coronary artery at reduced perfusion pressures, whereas nitroglycerin had similar effects even at normal perfusion pressures. In anesthetized closed-chest dogs, nicorandil and nitroglycerin produced an increase in the diameter of the conductive coronary artery (nicorandil < nitroglycerin). Nifedipine failed to produce dilatation of the conductive coronary artery in both preparations. In isolated ring preparations of conductive coronary artery, all three compounds produced relaxation of the potassium-induced contracture, but only nicorandil and nitroglycerin reversed the lanthanum-induced contracture.

Antiarrhythmic and electrophysiological effects of CH-200.

A new antiarrhythmic drug CH-200, 5-phenacyl-thieno[3,2-c]yridinium, was compared with procainamide and lidocaine in a two-stage coronary ligation arrhythmia model for its efficacy and electrophysiological properties. CH-200 suppressed arrhythmia in beagle dogs more effectively than did procainamide and lidocaine. The antiarrhythmic effects of CH-200 and procainamide developed slowly and lasted longer than those of lidocaine. Electrophysiological studies with CH-200 showed that it decreased max dV/dt of the action potential. This effect was dependent on the heart rate: the higher the rate, the stronger the effect. CH-200, procainamide and lidocaine prolonged the effective refractory period and this effect seemed to be responsible for suppressing the arrhythmia after coronary ligation. CH-200 and procainamide increased the frequency of ventricular pacemaker activity, while lidocaine decreased it. These effects appear to be unimportant for the antiarrhythmic effects.

Catecholamine Turnover in the Central Nervous System and Effects of Clonidine and Guanfacine

ABSTRACT Noradrenaline and dopamine levels in the cerebrum and cerebellum (C & C) and noradrenaline levels in the brain stem (BS) were higher, and the rate of diethyldithiocarbamate (DDC)-induced disappearance of noradrenaline in C & C and BS was lower in young spontaneous hypertensive rat (SHR) than in Wistar Kyoto rats (WKY). In the adult SHR and WKY noradrenaline and dopamine levels in C & C and BS were not different from each other. The noradrenaline level in BS of DOCA-hypertensive rats (DHR) was higher than that of age-matched Wistar Imamichi rats (WI), while noradrenaline and dopamine levels in C & C were not significantly different. In adult SHR and DHR, noradrenaline disappearance in C & C was slower than in WKY and WI, respectively, while faster in BS of SHR and DHR than of WKY and WI, respectively. In adult SHR, Clonidine and guanfacine produced no change in noradrenaline and dopamine content of the C & C, BS and corpus striatum (CS) when compared to WKY; however, they caused marked dose-dependent retardations of noradrenaline disappearance in C & C and BS following DDC and of α-methyl-p-tyrosine-induced disappearance of dopamine in CS. These results indicate the possibility that a higher level and an augmented disappearance of noradrenaline in BS are related to the development of hypertension.