An Analysis of the Cardiovascular Action of Levo-Epinephrine and Levo-Nor-Epinephrine

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Abstract
A prepn. was prepared which allowed the recording of the pressures at a number of strategic points in the system and of the total blood flow (with the exception of the coronary circulation). Thus, it was possible to obtain an insight into the effects of a cardiovascular drug on all the parameters of the circulation. Epinephrine can cause a contraction of the walls of the larger arteries and veins (decrease of constants of capacitance) tending to increase the blood flow, but at the same time produce an arteriolar contraction (increase in peripheral resistance) which has the opposite effect on the flow. The method of analysis proposed has advantages, since it gives an insight into the effects of a compound on the parameters of the circulation which are more basic indications of the drug action than the observed changes in the dependent variables. It was concluded that epinephrine in small doses can cause a dilatation of the arterioles producing an increase in flow and a decrease in arterial pressure. Higher doses cause an improvement of myocardial contractions and an increase in tone of the larger arteries and of the veins. Such changes may result in an increase in blood flow, an increase in systemic arterial pressure, and a decrease in atrial pressure. Moderate doses of epinephrine may have similar effects on the myocardium and on the large vessels, but in addition they may cause arteriolar constriction. Depending upon the dominance of the effect of the compound either on the heart and larger vessels or on the arterioles, the blood flow will rise or drop. All these changes cooperate, however, in increasing the systemic arterial pressure. Epinephrine in large doses may increase the flow and systemic arterial pressure to such a degree that the heart can maintain the necessary work output only under the stimulus of a developing systolic residue. The effect of the latter can override the effect of the compound on the myocardium, resulting in a greatly increased atrial pressure. In most expts. the differences between the effects of epinephrine and nor-epinephrine are small. In small doses which do not produce arteriolar contraction, nor-epinephrine tends to produce a more marked increase in tone of the larger vessels than epinephrine. Norepinephrine produces a constrictor effect of the arterioles at smaller concn. than epinephrine. In moderate doses norepinephrine seems to cause a larger arteriolar contraction and/or a smaller tone increase of the larger vessels than epinephrine. The effects of the 2 compounds on myocardial function and on the heart rate do not seem to differ materially.

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