6533b7d6fe1ef96bd1265d35

RESEARCH PRODUCT

Effect of coronary perfusion rate on the hydrolysis of exogenous and endogenous acetylcholine in the isolated heart

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description

1. The effect of perfusion rate on the hydrolysis of acetylcholine in isolated chicken hearts was studied by measuring both the spontaneous and the evoked output of endogenous acetylcholine into the perfusate in response to vagal stimulation and the arterio-venous difference of exogenous acetylcholine. 2. A decrease in the perfusion rate from 30 to 20 and 10 ml/min caused a graded and significant decline of both the spontaneous overflow of acetylcholine and the overflow evoked by stimulation of both vagus nerves (20 Hz, 1 ms, 40V) for 20 min. The spontaneous and evoked overflow at 30 ml/min were 2 and 3 times, respectively, the overflow at 10 ml/min. 3. Physostigmine (10−6M) raised both the spontaneous and the evoked acetylcholine outputs into the perfusate. The rise of the evoked output was much more pronounced at 10 ml/min (7.5-fold) than at 30 ml/min (2.5-fold) so that the differences in the output at these perfusion rates were abolished after inhibition of cholinesterase. 4. Although vagal stimulation in the presence of physostigmine caused an output of acetylcholine into the perfusate equivalent to the content of the heart determined before stimulation, no change of the cardiac acetylcholine content was observed. Thus the total acetylcholine content must have been resynthesized during the 20-min period of vagal stimulation. Physostigmine raised the acetylcholine content by the same extent, both before and after stimulation. 5. The arterio-venous difference of acetylcholine during infusion of this compound (10−7 M) for 10 min was increased from 37±8 to 56±7% (n=10) of the arterial concentration, when the perfusion rate was decreased from 30 to 10 ml/min. Physostigmine abolished the effect of the perfusion rate upon the appearance of acetylcholine in the effluent. Moreover, the arterio-venous differences were less than 5% after inhibition of cholinesterase. 6. It is concluded that extracellular inactivation of the parasympathetic transmitter of the heart is dependent on both the cholinesterase activity and the rate of the coronary flow.