Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Abstract

Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4-8 jug/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.KEY WORDS right bundle branch determinants of conductivity spontaneous phase 4 depolarization transmembrane action potential innervation of the heart • Early investigations indicated that cells of the specialized conduction system below the atrioventricular (AV) junction are unaffected by small concentrations of acetylcholine (1). Specifically, the slope of spontaneous phase 4 depolarization from cells of the bundle of His, bundle branches, and peripheral Purkinje fibers is reported to be essentially unchanged by the infusion of acetylcholine. A method of exposing the entire proximal portion of the specialized AV conduction system of the canine heart in vitro was devised by one of the authors (M.V.E.), and the regular observation of automaticity afforded the opportunity to reexamine certain aspects of this property.From the Krannert Institute of Cardiology, Marion County General Hospital, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.This work was supported in part by U. S. Public Health Service Grants HE-6308, HTS-5363, and HE-5749 from the National Heart Institute and by the Herman C. Krannert Fund, the Indiana Heart Association, and the AMA Committee for Research on Tobacco and Health. Drs. Bailey, Elizari, and Anderson are U. S. Public Health Service Trainees in Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.Received July 30, 1971. Accepted for publication November 29, 1971. The purpose of this paper is to report our studies of the effects of small doses of acetylcholine on spontaneity and conduction within the proximal portion of the HisPurkinje conduction pathways. MethodsAdult mongrel dogs of either sex weighing 15-20 kg were anesthetized with sodium pentobarbital (30 mg/kg, i.v.) and intubated; respiration was controlled with a Harvard respirometer. The hearts were excised rapidly through a right thoracotomy, and the portion of the septum containing the AV junction, the bundle of His, and both bundle branches was removed, placed in a Lucite muscle chamber, and superfused with oxygenated Tyrode's solution maintained at a temperature of 31 ± 0.2°C. Then the entire bundle of His was exposed from the nodal His (NH) region of the AV junction to the origins of both bundle branches. Portions of the proximal part of the specialized AV conduction system were isolated, when appropriate, by transection. The tissue was then allowed to stabilize for several hours until muscular contraction ceased and to minimize changes in diastolic depolarization as a function of time and in...

Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

“…However, there are conflicting data regarding the importance of direct vagal effects in the ventricular myocardium and the HPS. Several studies have shown that vagal stimulation and ACh infusion exert a negative chronotropic effect on His-Purkinje tissues in vitro and in vivo (52,(60)(61)(62)(63). In addition, ventricular refractory periods are shortened in response to atropine in patients pretreated with propranolol, suggesting a direct cholinergic effect in this tissue (64).…”

Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.

“…No other consistent effects on action potential characteristics were observed. Studies by other investigators have shown that ACh can increase maximum diastolic potential, 5 ' 6 rate of rise of phase 0, 5 action potential amplitude, 5 ' 6 and conduction velocity. 5 In both of these studies, preparations were used which had lower membrane potentials than those in our study prior to supervision with ACh.…”

“…Studies by other investigators have shown that ACh can increase maximum diastolic potential, 5 ' 6 rate of rise of phase 0, 5 action potential amplitude, 5 ' 6 and conduction velocity. 5 In both of these studies, preparations were used which had lower membrane potentials than those in our study prior to supervision with ACh. In reviewing the contents of Table 1, it is apparent that in our study small increases in MDP did occur with ACh; however, these are statistically insignificant.…”

“…Studies of isolated tissues indicated that ACh has no significant effect on the normal Purkinje fiber action potential or automaticity. 3 However, more recent studies have suggested that ACh does in fact decrease automaticity in the proximal 5 and distal 6 ventricular conducting system. Bailey et al 5 found that His-Purkinje preparations were hyperpolarized by ACh and that action potential amplitude, maximum rate of rise of phase 0, and conduction velocity were concomitantly increased (presumably as a result of increased membrane potential).…”

“…Bailey et al 5 found that His-Purkinje preparations were hyperpolarized by ACh and that action potential amplitude, maximum rate of rise of phase 0, and conduction velocity were concomitantly increased (presumably as a result of increased membrane potential). The rate of spontaneous impulse initiation of these preparations was decreased by ACh.…”