THE MECHANISM OF THE ATRIAL REFRACTORY PERIOD CHANGE PRODUCED BY OUABAIN

¹ Department of Pharmacology, University of Mississippi Medical Center, Jackson, Mississippi

The effects of ouabain on the atrial refractory period (RP) were investigated in the isolated rabbit atrium in an effort to uncover a possible explanation for the many contradictory statements in the literature concerning such effects. The response to ouabain was characterized by a latent period followed by a decrease in RP which reached a maximum at 20 minutes. Following this decrease, the RP again rose to reach a level above that of the initial control level by 60 minutes. This response was not affected by atropine, hexamethonium, or phenoxybenzamine. Atria treated with reserpine or the beta adrenergic blocking agent pronethalol showed only an increased RP in response to ouabain. The decrease was eliminated and the latent period shortened. The characteristic ouabain response could be restored to reserpinized atria by incubation of the atria with norepinephrine.

The data are interpreted to indicate that in the isolated system ouabain exerts two opposing actions on the RP: 1) a release of norepinephrine, which tends to decrease the RP, and 2) a direct action of ouabain itself tending to increase the RP.

The vagal stimulation produced by ouabain, resulting in a release of acetylcholine, will tend to decrease the RP and must also be considered in the intact animal.

The measured RP response to ouabain in any individual animal will depend on the relative contributions of these three factors.