Keitaro Hashimoto

The mechanism of sensitization of the ventricle to epinephrine by halothane

Abstract Epinephrine-induced ventricular arrhythmias were studied in dogs anesthetized with pentobarbital during inhalation of oxygen with or without halothane. Bigeminy or multifocal ventricular tachycardia was produced by intravenous injection of epinephrine when its positive chronotropic effect was at its maximum. These arrhythmias were readily induced under halothane which slowed the sinus rate. The severity and the duration of these arrhythmias were dependent on the supraventricular input which was conducted from the atrium and controlled by an electronic stimunator. Atrial driving at a sufficiently high rate could override these arrhythmias. This rate was almost the same as the maximal sinus rate which was attained by the same dose of epinephrine without halothane. Decrease of supraventricular input by destroying the sinus node also facilitated the induction of ventricular arrhythmia and the threshold dose of epinephrine was the same either in the presence or in the absence of halothane. It is concluded that the mechanism of sensitization to epinephrine by halothane to produce minor ventricular arrhythmia is mainly due to the slowing of the sinus rate by halothane and its direct effect on the ventricular myocardium is a cubsidiary factor.

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.

Cardiac irregularities induced by intracoronary injection of epinephrine and acetylcholine into various portions of the canine ventricle

Abstract Autoperfusion of the canine posterior septal artery (PSA), the anterior septal artery (ASA), and the anterior descending artery (ADA) were performed. A-V block was induced by acetylcholine, and P-R shortening or A-V junctional tachycardia was induced by epinephrine injected into either the PSA or the ASA. The results of this experiment confirmed the dual blood supply of the A-V junctional area from the two arteries. Epinephrine injected into the ADA induced multifocal ventricular tachycardia during halothane anesthesia. This arrhythmia was abolished by driving the atrium electrically at the rate observed before halothane anesthesia. Consequently, the slow heart rate induced by halothane probably plays some role in the induction of halothane-epinephrine arrhythmia, that is, the sensitization of the myocardium to epinephrine. The site of origin of this arrhythmia may be within the terminal Purkinje fibers, since only this tissue has latent pacemaker activity in that part of the myocardium supplied by the ADA. A-V junctional tachycardia induced by epinephrine injected into the ASA was also enhanced by halothane and abolished during atrial pacing, indicating that the A-V node is sensitized to epinephrine by halothane.

Pharmacological analysis of chronotropic responses of the S-A node to caffeine

Abstract The sinus node artery was perfused in situ in 12 dogs. Selective administration of caffeine into the sinus node artery produced double peaked positive chronotropic responses, i.e., initial rapid acceleration of the sinus rhythm followed by slow but long-lasting acceleration. The initial positive chronotropic response to caffeine was not suppressed by treatment with a β-adrenergic blocking agent, propranolol or H 56/28, or by treatment with tetrodotoxin whereas these substances effectively blocked the secondary positive chronotropic response. It is suggested that the initial positive chronotropic response to caffeine is a direct effect on the S-A node and the secondary positive response is due to catecholamine release from adrenergic nerve terminals by excitation of nerve fibers.