Nature of the Potentiating Substance in Cardiac Muscle

An extrasystole, rest, an increase in frequency, or above threshold stimulation with mass electrodes all potentiated the contractions of isolated cat papillary muscle and atrial appendage (but not strips from the posterior wall of the atria). The augmentation diminished or disappeared after the strips had been several days in the bath, after large doses of dibenamine, and after degeneration of the sympathetic nerve supply to the heart. In general, the augmentation phenomena were affected to about the same degree, which suggests a common mechanism. The results are consistent with our working hypothesis that all of the augmentation phenomena are due to intracardiac liberation of norepinephrine during each contraction, possibly from nerve endings. Evidence is presented that acetylcholine is released during activity in the cat papillary muscle as well as in the atria, and that the positive inotropic action of acetylcholine is probably due to the subsequent release of norepinephrine. Acetylcholine is apparently not a requisite for potentiation, however. The relative amounts of norepinephrine and acetylcholine liberated may determine whether augmentation or depression of contractility will be manifested.