Koroku Hashimoto

Cardiac actions of methoxamine with special reference to its antagonistic action to epinephrine.

The cardiac action of large doses of methoxamine and its antagonistic action to epinephrine were studied, using a dog heart-lung preparation. In doses of 4 mg. and above, methoxamine showed a marked negative inotropic action, while it produced only a slight decrease in the heart rate. Pretreatment of animals with 0.1 mg./Kg. of reserpine did not modify the inotropic action, but the decrease in the heart rate disappeared. Simultaneous with these changes, a decrease in the coronary flow and a rise of the pulmonary arterial pressure were observed. Methoxamine in doses of 1 mg. and more abolished both the positive inotropic and the positive chronotropic actions of epinephrine. The negative inotropic action of methoxamine was ascribed to a nonspecific, as yet undetermined mechanism, and the antagonistic action was ascribed to the competitive antagonism at the receptor site (thus methoxamine may be looked upon as a blocking agent of adrenergic β receptor). The weak negative chronotropic action was taken to be an expression of the blockade of the humoral effects of the intrinsic sympathomimetic amines.

Effects of halothane on automaticity and contractile force of isolated blood-perfused canine ventricular tissue.

The effects of halothane on canine ventricular automaticity and contractility were studied in intact and isolated heart preparations in which the right anterior papillary muscle and sinoatrial node of a recipient dog were separately perfused with arterial blood from a donor animal. One percent halothane inhaled by the donor dog decreased blood pressure and heart rate in the donor animal and sensitized the ventricle of the donor dog to the arrythmic effects of norepinephrine. One per cent halothane inhaled by donor dogs also produced negative inotropic and chronotropic responses in the isolated, perfused sinoatrial and ventricular oprparations, but had no effect on positive chronotropic or inotropic responses to norepinephrine or perivascular nerve stimulation. Norepinephrine administered to donor dogs produced no arrhythmia in either spontaneously beating or electrically paced recipient hearts even though producing ventricular fibrillation in the donor. The results suggest that re-entry mechanisms play an important role in halothane-catecholamine-induced arrhythmias.

The physiological and pharmacological studies on the isolated bullfrog's heart.

The isolated bullfrogs heart was perfused with heparinized blood and then its O2-uptake, CO2-production, cardiac output, venous and aortic pressure, and EKG were able to be measured simultaneously by our apparatus, which was described in detalis.