Acetylcholine-induced reversal of canine and feline atrial myocardial depression during stretch, cardiac failure, and drug toxicity.

Abstract

Microelectrode and isometric recording techniques were used to evaluate the effects of acetycholine (ACh) on depressed isolated preparations of dog and cat atrial muscle. Atrial muscles were maintained at 36-37 degrees C with warmed Tyrode's solution and were stimulated at frequencies of 30 or 60/min. Depolarization to resting potentials of approximately -50 mv was noted (1) after excessive stretch was applied, (2) in muscles obtained from cats in overt right heart failure, and (3) during exposure of the muscles to excessive concentrations of acetylstrophanthidin or lidocaine. Depolarized muscles demonstrated action potentials of smaller amplitude and rate of rise. Exposure to ACh (2.7 X 10(-6)M) had a minimal effect on resting potential in normal dog and cat atrial muscle and was accompanied by significant negative inotropic actions. The same concentration of ACh markedly increased resting potential and action potential amplitude and induced positive inotropic effects in depolarized muscles; these effects also occurred during beta-adrenergic blockade. We suggest that the positive inotropic effect of ACh in depressed muscles may result from (1) a more synchronous contraction of cells within each muscle, (2) recruitment of previously quiescent cells in contraction, (3) possibly increased calcium inflow in individual cells during depolarizations of greater magnitude, and (4) an increase in the number of interacting sites between actin and myosin after resting potential is improved.