FURTHER STUDIES OF THE EFFECT OF EPHEDRINE ON THE CIRCULATION

¹ From the Laboratories of Pharmacology and Physiology, University of Wisconsin, Madison, Wisconsin

1. Ephedrine given intravenously in anesthetized dogs in the dosage from 0.005 to 30 mgm. per kilo, raises arterial blood pressure, the optimum dose lying between 1 and 10 mgm. per kilo. Larger doses usually lower the blood pressure. The change in pressure does not entirely depend on the quantity given, but also on the condition of the animal prior to its administration. Repeated intravenous injections of optimum doses, when given at intervals of twenty-five minutes, are not as effective as the first in raising blood pressure in regard to duration and height. Repeated intravenous injections of sub-optimum doses, on the other hand, when given close together will show a summative effect in elevating pressure.

2. Ephedrine in stimulating doses (those that raise blood pressure) given intravenously; intramuscularly, orally or subcutaneously, in anesthetized or non-anesthetized animals with intact vagi usually slows the pulse rate. Acceleration always takes place when the vagi are paralyzed by atropine. Ephedrine in depressing doses (those that lower the blood pressure) always decreases the pulse rate irrespective of the condition of the vagi.

3. Prolonged vasoconstriction is observed in the perfusion of isolated mammalian organs. In plethysmographic studies, it is found that the splenic vessels are constricted, the renal vessels first constricted then dilated, and the intestinal and leg vessels usually dilated. The rise of blood pressure cannot therefore be entirely due to peripheral constriction. Cardiac stimulation, as concluded before, is one of the factors.

4. Ephedrine sulphate applied locally to the frog's heart may accelerate the heart rate by a few beats per minute in a concentration of 1:1000, but depresses it both in rate and amplitude in a concentration of 1:100. In the perfusion of the terrapin's heart, ephedrine sulphate may accelerate the rate by a few beats per minute in a concentration of 1:10,000, but produces bradycardia and usually a decrease in amplitude in concentrations of 1:1000 and 1:100, with frequent occurrence of auricular extrasystoles, and finally passing to a state of feeble contractions followed by standstill at diastole. Perfusion experiments of the isolated rabbit's heart by Langendorff's method shows that ephedrine sulphate dissolved in Locke's solution stimulates the heart by increasing both the rate and the strength of contractions in a concentration of 1:100,000, but depresses both in concentrations of 1:10,000 and 1:5000. Concentrations of 1:2000 and 1:1000 bring about partial block, the latter finally causing stoppage. Colloidal solutions, such as peptone or horse serum added to Locke's solution, reduce the depressant action of ephedrine.

5. By electrocardiographic studies in non-anesthetized and anesthetized dogs, small doses of ephedrine given intravenously cause nothing more than some alteration of the T wave—flattening, reversion or occasionally augmentation. Massive doses in dogs and rabbits appear to depress the automatic and conductive system in a descending order; that is, from the S-A node to the terminations of the Purkinje system. There is, therefore, an occurrence of bradycardia, prolongation of the P-R interval, partial A-V block, nodal rhythm, ventricular escape or extrasystoles, bundle branch block and finally ventricular fibrillation.

6. With the vagal reflex abolished in anesthetized dogs, ephedrine is shown to increase the cardiac output during the rise of blood pressure and increase of pulse rate. It decreases slightly the diastolic size of the heart, as measured from x-ray plates, which, however, does not seem to be sufficient to overbalance the increase of volume output since a very marked increase of pulse rate is produced.

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