The formation of acetylcholine in the heart; its effect on the systemic output and its importance for auricular fibrillation caused by aconitine

Abstract

Burn & Walker (1954) described experiments carried out in the heart-lung preparation of the dog which indicated that acetylcholine (ACh) was liberated in that preparation without stimulation of the vagus nerves. They observed that the addition of substances like eserine or neostigmine to the blood, even in low concentration, caused a large fall in the rate of the beat. These substances inhibit the destruction of acetylcholine, and since in addition the fall in rate which they caused was abolished by a small amount of atropine, the conclusion was drawn that the effects observed were due to continuous liberation of small amounts of ACh. Briscoe & Burn (1954) demonstrated that the isolated heart of the rabbit formed ACh, and it was therefore reasonable to suppose that the ACh liberated in the heart-lung preparation came from the heart and not from the lungs.Burn, Vaughan Williams & Walker (1955a) showed that in the heart-lung preparation ACh, infused at constant rate, prolonged the P-R interval, reduced the systemic output of blood and produced A-V block. They also showed that the application of a few stimuli to the auricular appendage during the infusion of the appropriate amount of ACh caused auricular fibrillation. In a later paper (1955b) they found that the addition of inhibitors of cholinesterase to the heart-lung preparation without ACh infusion had similar effects. The P-R interval was prolonged, the systemic outflow was reduced and, in sufficient concentration, there was A-V block. When stimulation was applied to the auricle, the rate at which A-V block began was much reduced. Finally, after stimulation at higher rates in the presence of eserine or paraoxon, auricular fibrillation occurred for a length of time which depended on the concentration of the inhibitor. All this evidence gave further support to the view that ACh was liberated by the heart.

The release of substances like acetylcholine and adrenaline by the isolated rabbit heart

“…When the hearts were driven electrically by stimuli applied near the apex of the ventricle at a rate nearly four times as fast as the spontaneous rate, the amount of ACh-like substance was two and a half times as great. This result agrees with the finding of Burn, Vaughan Williams & Walker (1956) in the heart-lung preparation of the dog, who also drove the heart electrically by stimuli applied to the apex of the ventricle. They found that when stimulation was performed in the presence of eserine, at the end of stimulation the spontaneous rate was slower and the P-R interval was increased considerably.…”

“…Evidence has also been obtained that the perfused heart liberates adrenaline and noradrenaline. This also conforms with the results of Burn et al (1956) in the heart-lung preparation; for they found that, when they injected atropine, driving the ventricle by stimulating the apex then resulted, when the stimuli were stopped, in a raised spontaneous rate which persisted for more than 5 min.…”

Electrophysiological Effects of Diphenylhydantoin on Canine Purkinje Fibers

“…Agents which shorten the action potential previously have been associated with an increased likelihood of extrasystoles and fibrillation, in both atria and ventricles. Burn et al (27,28) discussed atrial fibrillation induced by electrical stimulation or aconitine in the presence of acetylcholine. They felt that fibrillation was due to different cardiac fibers getting out of phase in the presence of shortened repolarization so that re-excitation could occur.…”

Excitation and inhibition of rabbit atria by the vagus nerves

“…It remains to consider why, in some preparations, these contractions were followed by the resumption of a normal rhythm. There is now a good deal of evidence that the beating heart, isolated from vagal influences, liberates acetylcholine (Briscoe & Burn, 1954;Burn & Walker, 1954;Day, 1956;Burn, Vaughan Williams & Walker, 1956). The acetylcholine which is thus liberated is most probably formed by choline acetylase, the presence of which was demonstrated by Comline (1946).…”

“…

Recently MeEwen (1956) has described experiments on the rabbit heart isolated with vagus nerves; he also set up atria with vagus nerves andfound that vagal inhibition was still obtained even after 40 hr.Marshall & Vaughan Williams (1956) studied the effect of cooling on isolated rabbit atria and found that when the temperature fell to a point which varied for different preparations, usually between 15 and 200 C, small potentials could be recorded by a pair of external electrodes placed on the pacemaker, but these were not propagated and caused no tension change. They found that when acetylcholine (10-7 g/ml.)

…”