EFFECT OF TETRODOTOXIN AND DL-PROPRANOLOL ON OUABAIN-INDUCED ARRHYTHMIAS
1973 年 20 巻 4 号 p. 225-233
詳細
1973 年 20 巻 4 号 p. 225-233
The effects of tetrodotoxin and dl-propranolol on ouabain-induced arrhythmias were investigated in in vivo and in vitro experiments. In ECG studies, ouabain given to rats successively every 2 min (3 mg/kg i. v.) caused ventricular arrhythmias with prolongation of the P-Q interval. Pretreatment of tetrodotoxin (0.25-4.0 μg/kg i. v.) antagonized dose-dependently the cardiotoxicity of ouabain. Pretreatment of dl-propranolol, however, rather worsened conduction disturbances by ouabain, although the drug prevented completely the ventricular tachycardia. In in vitro studies, the effects of these drugs were investigated on various physiological parameters such as automaticity of interventricular septal strip, functional refractoriness and vulnerability of ventricular muscle. Successive addition of ouabain into bathing medium produced a transient decrease followed by a progressive increase in automaticity in the later stage. In the presence of tetrodotoxin, the time course of the ouabain-induced biphasic change in automaticity was extremely delayed. Propranolol abolished the later increase in automaticity by ouabain and only progressively decreased the automaticity resulting in a final loss of spontaneous contractility as digitalization proceeded. Further, ouabain-induced shortening of functional refractory period was prevented by propranolol, but not by tetrodotoxin. Ventricular fibrillation threshold was elevated by tetrodotoxin but not by propranolol, whereas both the drugs could antagonize the ouabain-induced enhancement of ventricular vulnerability. The antiarrhythmic action of tetrodotoxin was discussed in comparison with that of dl-propranolol, and possible ionic mechanisms underlying the antidigitalis action of tetrodotoxin were suggested.
