A Depressant Effect of Acetylcholine on the Idio‐ventricular Pacemaker of the Isolated Perfused Rabbit Heart

Abstract

In Langendorff preparations of the isolated rabbit heart, excision of the atria and severance of the atrio-ventricular bundle resulted in the onset of idio-ventricular rhythm at a rate much below the original sino-atrial rate. The mean decrease in rate in twelve experiments was 61%. Acetylcholine perfusion decreased the idio-ventricular rate still further. Physostigmine augmented this effect while atropine prevented or abolished it. Similar results were obtained with a rat heart. The results indicate that a cholinergic receptor mechanism is present at pacemaker sites in mammalian ventricles. However, when rabbit ventricles, beating under atrio-ventricular nodal rhythm or idio-ventricular rhythm, were cooled to the point of cardiac arrest, acetylcholine failed to cause reappearance of the cardiac beat.Acetylcholine has been shown to affect the transmembrane atrial resting and action potentials in a number of species (Cranefield and Hoffman, 1958), and these effects present a basis for understanding the actions of this substance on rate, conduction velocity, and refractory period of atrial tissue. Effects on the transmembrane action potential of the frog ventricle have also been demonstrated, but experiments in which the effect of acetylcholine on the mammalian ventricular action potential was examined have proved negative (Brooks, Hoffman, Suckling, and Orias, 1955). Further, the generally accepted fact that the ventricle does not receive cholinergic innervation has been suggested as a reason for these negative results (Hoffman and Suckling, 1953;Brooks et al., 1955). The experiments presented here indicate that acetylcholine can decrease the idioventricular rate of the isolated perfused rabbit and rat heart, and that this effect is augmented by physostigmine and is reversed or prevented by atropine. The effect of acetylcholine on isolated rabbit ventricles cooled to the point of cardiac arrest was also examined. The results of 19 experiments are described. by McEwen (1956). The heart rate was measured from the electrocardiogram, which was recorded by leads from the two ventricles. In a few early experiments, heart rate was counted with the aid of a stopwatch by observing ventricular contractions on a kymograph drum. For the production of atrio-ventricular nodal rhythm the atria and interatrial septum were excised at the level of the atrio-ventricular groove. In the experiments on idio-ventricular rhythm, the atrio-ventricular bundle was severed by an additional cut in the inter-ventricular septum. Drugs employed were added to the bottles containing the perfusion fluid. Drug concentrations are expressed as g./l. of the base. When hearts were cooled, this was accomplished by the gradual adding of tap water and ice to the water-bath in which the perfusion coil was immersed. The rate of cooling was about 1/min. RESULTSIdio-ventricular Rhythm and the Effect of Acetylcholine Table I shows the change in rate produced in the isolated perfused rabbit heart by excision of the atria and severance of the atrio-ventricular b...

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea‐pig heart

“…The hearts were stimulated at 1P25 Hz (5 ms duration, voltage 10% or less above threshold) after the elimination of atrial and nodal pacemakers according to the method of Benforado (1958). For these experiments 3H-ouabain 5 x 10-6M was perfused for 15 min either alone or in the presence of a second agent through hearts that previously had been equilibrated for the usual 64 min period.…”

Rhythm generating mechanisms in rat sino-atrial node and ventricle

“…On carefully cutting off the right atrium and severing the atrio-ventricular bundle by incising the inter-ventricular septum of the mounted and perfused heart, the heart stopped and then started to beat on its own (without any pacing). The new heart rate was low compared to the initial SA nodal rhythm and was considered as the idio-ventricular rhythm (Benforado, 1958). The basal heart rate in ventricular rhythm was 57 ± 16 (n= 21).…”

“…Hearts were isolated and perfused with Physiological salt solution (PSS) with a cannula placed in the aorta above the aortic valve, to perfuse the coronary arteries (Langendorff preparation). For experiments on idio-ventricular rhythm the right atrium was carefully excised after cannulation and the atrio-ventricular bundle was severed by a cut in the inter-ventricular septum (Benforado, 1958). ECG electrodes in contact with the surface of heart, were used to record the surface electrogram.…”

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

“…ACh also has been shown to decrease idioventricular rate in isolated rabbit hearts. 8 Complete data on dose-response relationships are also lacking for these studies, however.…”