The relation of the choline cycle to cardiac decompensation: Acetylcholine metabolism in the dog heart-lung preparation

Abstract

1. 1. The cholinesterase occurring in dog heart muscle is predominantly of the nonspecific type. 2. 2. Pentobarbital failure is often accompanied by a decreased cholinesterase activity in the heart muscle. 3. 3. Ouabain administration to the heart decompensated by pentobarbital results in a maintenance of or an increase in cholinesterase activity concomitantly with its positive inotropic effect. 4. 4. Decompensation can be produced by large doses of penicillin G, physostigmine, or diisopropyl fluorophosphate, agents known to be inhibitory in the choline cycle. Failure by penicillin G is poorly remediable by ouabain. Ouabain is effective to a variable degree in physostigmine and diisopropyl fluorophosphate failure. 5. 5. Choline in large doses is positively inotropic in the atropinized dog heart-lung preparation failed by any of these compounds. Its administration hinders subsequent failure by physostigmine or pentobarbital, and results in a partial relief of physostigmine inhibition of cholinesterase. 6. 6. Benzoylcholine has positive inotropic activity in failure produced by penicillin G and impedes decompensation by physostigmine. Benzoylcholine inhibits the positive inotropic effect of choline. 7. 7. Ouabain may function to relieve esterase inhibition or (less likely) to release acetylcholine from its protein complex. 8. 8. The hypothesis is offered that these types of decompensation are the result of interference with the choline cycle as it pertains to cell membrane integrity, and that other types of decompensation may have a similar etiology.