Toshiyuki Shibuya

Effective Plasma Concentrations of Antiarrhythmic Drugs Against Sustained Halothane-Adrenaline Arrhythmia in Dogs

Summary We determined the minimum effective plasma concentrations of several antiarrhythmic agents against canine halothane-adrenaline arrhythmia. Sustained ventricular tachycardia was produced by continuous adrenaline infusion at rates of 1.5 to 4 μg/kg/min under 1.5% halothane anesthesia. Procainamide, 20 mg/kg, produced ventricular fibrillation in three of nine dogs. Disopyramide, 3 mg/kg, suppressed the arrhythmia in nine of 11 dogs at a minimum effective plasma concentration of 4.2 μg/ml, but produced ventricular fibrillation in the remaining two dogs. Phenytoin, 5 mg/kg, was effective at a minimum concentration of 12 μg/ml. Lidocaine, 10 mg/kg, suppressed the arrhythmia at a minimum concentration of 15 μg/ml, which is much higher than the human toxic plasma level. These drugs may have suppressed the adrenaline arrhythmia by inhibiting the sodium channel, because their effective concentrations were very close to membrane-stabilizing concentrations in vitro. Small doses of 30 μg/kg propranolol and 0.1 mg/kg N-696, two β-blockers, and 0.1 mg/kg verapamil, a calcium channel blocker, yielding a concentration of 0.03 μg/ml, suppressed the arrhythmia, probably by indirectly or directly blocking the calcium channel.

Effects of parathyroid hormone and related polypeptides on the heart and coronary circulation of dogs.

Summary The effects of parathyroid hormone and related polypeptides on the heart were examined using the canine heart-lung preparation supported by a donor. Synthetic bovine parathyroid hormone (PTH) containing 34 amino acids [PTH-(1–34)] and natural bovine PTH containing 84 amino acids [PTH-(1–84)] showed slight positive chronotropic and inotropic action and prominent coronary vasodilator action. The effects of the two compounds were very similar. The cardiac stimulatory action was not blocked by pindolol. The coronary vasodilation occurred without increase in the myocardial oxygen consumption, suggesting that it is due to a direct action on the coronary vasculature. All effects occurred soon after intra-arterial injection, lasted only about 20 min, and were not accompanied by changes in plasma Ca and Pi levels. Fragments of PTH, PTH-(24–34) containing 11 amino acids, PTH-(24–28) containing 5 amino acids, and PTH-(25–27) containing 3 amino acids showed very weak transient coronary dilatory action without cardiac stimulatory effects.

A possible autonomic modulation of sinus node recovery time in overdrive suppression test

The effect of blood pressure fall on sinus node recovery time (SNRT) was studied in 17 patients during the overdrive suppression test. Their maximal SNRT was less than 150% of the mean P-P interval of the control state (=SCL) and CSNRT (=SNRT-SCL) was less than 550msec. Blood pressure was found to fall in about a half of the patients at a high pacing rate. Concomitantly, SNRT was found to shorten in those who showed such a fall in blood pressure. The subjects were then divided into two groups; one with a shorter SNRT at 150bpm than at 90bpm of pacing rate and the other without such shortening. The changes in SNRT and CSNRT were both significant in the first group (p less than 0.02 and p less than 0.001, respectively). The fall in blood pressure at 150 bpm was significant in the group with shortened SNRT and CSNRT and it was larger than in the other group: 23 +/- 14mmHg vs. 1 +/- 5mmHg (p less than 0.001). This result suggests a possible modulation of SNRT by a fall of blood pressure via baroreflex.

Ventricular arrhythmia with postural dependency

Ventricular arrhythmias associated with recumbency were noted in a 17-year-old man with mild idiopathic myocarditis. These arrhythmias were refractory to several anti-arrhythmic drugs. Frequent ventricular arrhythmias were reproducibly recorded in the supine position and in a 15 degree tilt from the horizontal, while they were completely abolished in positions tilted more than 30 degrees from the horizontal, at which time sinus rate increased to more than 70 beats/min. The ventricular arrhythmias were suppressed during treadmill exercise and markedly aggravated when the underlying sinus rate was decreased during sleep or lying flat in bed. The arrhythmias were entirely abolished by atropine 1 mg. Furthermore, they were suppressed during atrial pacing at the rates of 80 and 90 bpm. Ventricular tachycardia could not be induced by programmed right ventricular stimulation. The appearance of postural arrhythmias in this patient correlated with relative bradycardia suggesting that they may be related to enhanced vagal nerve activity.