Abstract
The fact that 1-2-4 dinitrophenol, which greatly accelerates the oxidative metabolism of tissues, increases blood sugar concentration has been reported by Magne, Mayer and Plantefol 1 and confirmed by Hall, Field, Sahyun, Cutting and Tainter. 2 Since the large increase in oxygen usage of the tissues provoked by the drug might readily outstrip the ability of the respiratory and circulatory mechanisms to deliver oxygen and so lead to general bodily asphyxia, it seemed possible that the hyperglycemia might be of such asphyxial origin. The experiments described herein were designed to test this hypothesis.
Cats, anesthetized with pentobarbital, received doses of 15 or 20 mg. per kilo of 1-2-4 dinitrophenol intramuscularly in the form of its sodium salt. Blood samples at half-hour intervals were analyzed for sugar by the method of Sahyun, 3 for oxygen and total carbon dioxide content by the manometric method of Van Slyke and Neill, 4 and for plasma pH by the colorimetric method of Hawkins. 5 Five experiments with 20 mg. per kilo, 2 with 15 mg. per kilo and 4 controls without any drug were performed. Within each group, the experiments agreed with each other satisfactorily. The results in animals with the higher dose and in the controls are presented in Table I. The animals receiving 15 mg. per kilo gave values intermediate between those of the other groups.
From our results there is no indication of the development of asphyxia under the influence of dinitrophenol; the oxygen content of the blood is unchanged, the total carbon dioxide content falls, while the plasma pH rises. The findings thus support our 2 earlier conclusion that, at least before the terminal collapse sets in, the drug produces neither anoxemia, asphyxia nor acidosis. They are also in agreement with the determinations of plasma pH made by DeEds, 6 employing the glass electrode. The tendency to acapnia and alkalosis, which has appeared in these experiments, is no greater in the experiments with the drug than in the controls. The fact that the usual metabolic response was present and vigorous is attested by the marked increases in rectal temperature and respiratory rate.
In spite of the absence of asphyxia, there developed a marked hyperglycemia, the rise in blood sugar being approximately 3 times as great as that in the controls. The difference of the means of the final blood sugar values between the dinitrophenol animals and controls was 73.85 mg. per 100 cc. Since this difference exceeds its own probable error by 4.4 times, it is statistically significant.
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