In order to investigate the pathologic physiology of coronary insufficiency of neurohormonal origin, the experimental studies were carried out on dogs. The relationships among cardiac work, cardiac oxygen uptake, cardiac mechanical efficiency and electrocardiograms, and the effects of administrations of adrenaline and noradrenaline and of electrical stimulations of the cervical and spinal sympathetic nerves, were studied. In an early stage of all experiments, the electrocardiogram showed a coronary insufficiency pattern in accordance with increase in cardiac efficiency. In many cases, this insufficiency pattern disappeared with restoration of the original state or decrease in cardiac efficiency.

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As a toxic manifestation of digitalis ten episodes of paroxysmal atrial tachycardia with block, five episodes of nonparoxysmal A-V nodal tachycardia with block, two episodes of paroxysmal A-V nodal tachycardia and one episode of atrial flutter with block were observed in fourteen cases. Excessive dosage of digitalis, long-standing heart disease and siginificant potassium depletion resulting from the use of diuretics appeared to have precipitated these arrhythmias. Possible mechanisms operating in the production of the arrhythmias were discussed with reference to potassium and the existence of nonparoxysmal type of atrial tachycardea was suggested.

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Recently some observations concerning to the antiarrhythmic action of phenothiazine derivatives especially chlorpromazine are reported. The first observation of the antiarrhythmic activity of chlorpromazine was reported by Courvoisier (1953), Kawasaki has demonstrated a suppressive effect of this drug on ectopic excitation of heart muscle produced by experimental myocardial infarction and barium intoxication in dogs. In this paper the author attempts to find a relationship between antiarrhythmic potency and chemical structure of phenothiazine derivatives and to evaluate the clinical effectiveness of chlorpromazine alone or the combined therapy with procaine amide and quinidine on various types of arrhythmias. A) Screening Method The extrasystoles were evoked in adult healthy dogs each weighing about 10kg, by intravenous injection of thiopental sodium in a dose of 0.025kg and 2% barium chloride solution in a dose of 3 mg/kg respectively. These extrasystoles continued about 60 minutes. For screening of antiarrythmic activity, a drug to be tested is injected intravenously immediately after a definite provocation of experimental arrhythmia. A positive result represents a complets cessation of arrhythmia within one minute after injection of a test material. Twenty-three preparations of phenothiazine delivatives were tested by this method. B) Relationship between antiarrhythmic action and the chemical structures 1) Most potency group : 4695R.P. was the most potency one among the phenothiazine delivatives in this experiments (Table I). The minimum effective doses was 0.1mg/kg, about one tenth that of chlorpromazine. 2) Moderate potent group : Chlorpromazine, Promazine, Acepromazine, were classified in this group. Minimum effective doses were about 1mg/kg. 3) Less potent group : 7024 R. P. Trimeprazine, 4909 R. P. Chlorpromazine S oxide, . . . These pharmacons were classified in this group. Minimum effective doses were varying from 3mg/kg to 100mg/ kg. As shown in Table I, the substistution of R (10 position of phenothiazine nucleus) has a great influence on their antiarrhythmic potency. By increasing or decreasing the number of C atoms or substitution to isoaliphatic chain in dimethylamino propyl radical of R position of chlorpromazine, their potencies were significantly decreased.

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