Abstract
It is taught that epinephrine is much less effective by hypodermic or intramuscular injection than by the intravenous route. These differences are due to the rate of absorption, and this in turn to the vasoconstriction (Sollmann 1 ). The unabsorbed epinephrine at the site of injection is apparently not destroyed, for the local blanching may persist from one to 8 hours (root of rabbit's ear, Auer and Meltzer, 2 Meltzer and Auer 3 ; scarified skin, Sollmann and Pilcher 4 ). When this epinephrine becomes gradually absorbed, it exerts its systemic actions. (Fornet, 5 Lyon 6 ). It follows therefore, that if epinephrine were administered by a route such that it be slowly absorbed, its action would not be as sudden as by the intravenous route.
During an experiment in which epinephrine was injected subcu-taneously in the rat, a considerable percentage of the animals showed skin changes at the site of injection, ranging from loss of hair to necrosis and, in a few cases, gangrene. As the experiment included the use of various doses, a record of the animals was kept with respect to size of the dose of epinephrine and degree of skin change.
The epinephrine was diluted with isotonic sodium chloride so that 1 cc. contained 0.4 mg. The full dose given was 0.1 mg. per 250 gm. of rat. In the case of the 1/2, 1/4, 1/8 doses, the proper dilution was made. Abbott's epinephrine hydrochloride was used throughout the experiment.
Table I shows the relative changes with the various doses.
The question arose as to whether these changes were due to the vasoconstrictor effect of the epinephrine or the acid which it contains, The acidity of our sample was determined by means of the hydrogen electrode. A solution of the corresponding strength of HCl was made and amounts equivalent to the quantities contained in the full dose of epinephrine were given subcutaneously. Forty-two rats were used. Twelve showed very slight hair loss but in no case, any signs of necrosis. It seemed, therefore, that the extensive skin effects were due to the epinephrine itself.
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