The difficulties in the way of injection may now be considered more fully. A lethal dose of alcohol injected into the stomach or under the skin of an animal becomes lethal only after it has been absorbed into and distributed by the blood stream. Hence the importance of knowing whether the alcohol is absorbed promptly so as not to undergo loss or change in the tissues. In a word the rate of absorption must be rapid.
If also by injecting a lethal amount of alcohol under the skin or into the muscles, serious secondary injuries, such, for example, as abscesses and the like, result, a source of error is possible; for a dose of alcohol under the toxic equivalent aided by these secondary influences might thus produce death.
It was evident to Joffroy and Serveaux that in order to prevent errors arising from the rate of absorption and to reduce to lowest terms the danger of secondary injuries, a method should be employed which would insure that the entire amount of alcohol be in the blood at the same time. This could be accomplished in only one way, that was by adding the alcohol directly to the blood stream. They therefore turned their attention to intravenous injections.
While this method of adding the alcohol directly to the blood stream would control the rate of absorption and largely allay secondary injuries, yet it was found productive of errors the overcoming of which was imperative to an accurate measure of toxicity. In the first place it has been shown that if alcohol be injected too rapidly injuries both to the veins and to the viscera arise. On the other hand, if it be added too slowly, a loss of alcohol may occur through the kidneys and other ways of elimination.
The first problem of Joffroy and Serveaux was to find a way by which the injection could be made at constant pressure. This was accomplished by substituting for the Hypodermic syringe which had been generally used the "flaçon de Mariotte." This gave a constant pressure which was easily regulated at any time during the experiment. By injecting one cubic centimeter per minute for each kilogram of body weight they found no injury occurring either to the veins or to the viscera. With this rate it was also found that the entire amount could be injected before any considerable time had elapsed for elimination to take place.
With the error of rate of injection thus controlled they were ready to try the measure of toxicity. A series on rabbits gave discouraging extremes varying from 4.33 to 13.18 cubic centimeters per kilogram necessary to kill.[1] With variations so great as nearly 3 to 1 it was evident
- ↑ The exact amounts were as follows: 4.32 c.c, 8.92, 7.26, 12.18, 6.35, 8.44, 4.90, 7.54 c.c. per kilogram.
