THE ACTION OF RAUWOLFIA ALKALOIDS ON THE HEART RATE AND ON THE FUNCTIONAL REFRACTORY PERIOD OF ATRIO-VENTRICULAR TRANSMISSION IN THE HEART-LUNG PREPARATION OF THE DOG

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The heart-lung preparation of the dog was used in an examination of the action of 10 rauwolfia alkaloids on the heart rate, the functional refractory period of atrio-ventricular transmission and the A-V propagation time.

Two distinct pharmacological groups were found. One group, consisting of ajmaline, serpentine, aricine, reserpinine and -yohimbine, caused a decrease in heart rate accompanied by prolongation of the functional refractory period of A-V transmission and of the A-V propagation time.

The second group consists of the reserpinetype alkaloids—raunescine, isoraunescine, deserpidine, reserpine and rescinnamine. In the early period of their action the heart rate was increased and the functional refractory period and A-V propagation time were shortened. After 90 to 150 minutes, using a dose equivalent in effect to 3 mg reserpine, the heart rate fell while the functional refractory period and the A-V propagation time returned towards their original duration and were frequently further prolonged.

Raunescine, deserpidine, reserpine and rescinnamine amine lacked this transient cardioaccelerator and facilitating action on A-V transmission in experiments where the HLP was depleted of intrinsic sympathomimetic amines by previous treatment of the experimental animal with reserpine. Instead, slowing of the heart and prolongation of the functional refractory period and of A-V propagation time occurred under these conditions.

Both groups of rauwolfia alkaloids possess a depressant action on heart rate and A-V transmission. The transient cardioacceleration and facilitation of A-V transmission found with the reserpine-type group is explained by release from the heart of sympathomimetic amines, especially norepinephrine, which are known to cause these effects. The depressant action of the reserpine-type alkaloids is thus concealed until the release of sympathomimetic amines is no longer sufficient to counteract it.

The retarding action of the rauwolfia alkaloids on A-V transmission distinguishes their action from that of veratramine which also decreases the heart rate, but in equivalent rate-decreasing doses is known to have no effect on A-V transmission.