Abstract
We have shown 1 that bilateral nephrectomy greatly modifies the action of barbiturates in dogs; they do not recover from barbital, but do so from other barbiturates such as nembutal, pernoston, etc. As a further extension of this study, we used nephropathogenic agents to produce tubular lesions in mammals and investigated the action of barbiturates in animals with nephrosis. Dogs and rabbits were used for these experiments.
A. Tartaric Acid. Two dogs received 600 mg. of tartaric acid (neutralized with sodium carbonate) per kg. subcutaneously and subsequently given 225 mg. of sodium barbital per kg. by vein. The recovery from anesthesia was delayed, but the total excretion was but slightly subnormal (71-76%). After complete recovery and stoppage of excretion, the same animals, now showing evidence of grave tubular lesions, were again given 225 mg. of sodium barbital per kg. intravenously. They did not recover from the anesthesia and excreted less than 2% of the drug. Histological studies showed almost complete tubular disintegration, the glomeruli remaining fairly intact. Animals receiving 600 mg. of tartaric acid but no barbital do not become anesthetized and outlive the barbitalized animals. (See also Underbill, Wells and Goldschmidt. 2 )
B. Uranium Acetate. Three dogs and 2 rabbits were given 2 mg. uranium acetate in a 0.1% solution intravenously in divided doses over a period of 2 days. These animals did not recover from the depression produced by 225 mg. of sodium barbital per kg. by vein and excreted 41%, 38%, 8.7%, 2.3% and 1% of the drug respectively. The concentration of barbital in the urine was 1.0 mg. per cc, or less. Two dogs and one rabbit received in addition to uranium and sodium barbital, from 35 cc. to 50 cc. of a 10% glucose solution per kg. intravenously, excreting 56%, 38%, and 18% of the drug in the urine. Even though there appears to be an increase in the percentage of elimination in the diuretic animals, they never recovered from the barbital narcosis. The concentration of barbital in the urine was lower than in the non-diuretic animals. None of these animals, whether they were given glucose or not, ever recovered from barbital anesthesia and died within 114 hours following the administration of barbital. Three dogs similarly treated with uranium acetate, recovered within the usual periods from nembutal, pernoston, and neonal anesthesia.
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