450 E. V. FLOCK AND J. L. BOLLMAN 
fistula’ are often as great as those in dehepatized dogs, and much of the increase is 
due to glutamine content. Glutamine is also increased many-fold in the cerebrospinal 
fluid where its concentration greatly exceeds that in blood plasma. 
Increases in content of glutamine may be produced in the brain by other methods 
than removal of the liver or alteration of the circulation to the liver. Small increases 
have been produced by parenteral administration of glutamine into the brain of 
rats’: ° and dogs!”. Elevated levels of glutamine in the cerebrospinal fluid have also 
been produced by oral administration of glutamine!!. DE RuIssEAu ef al.1® have 
produced rapid increases in glutamine of the rat brain by administration of lethal 
doses of ammonium salts. Protective doses of arginine with or without glutamic 
acid and a-ketoglutaric acid, which increased the survival time of these rats, did 
not prevent the large increases in glutamine in the brain. EISEMAN et al.}3 adminis- 
tered 1° ammonium hydroxide in lactate—Ringer’s solution to dogs by bilateral 
carotid infusion and found that the content of glutamine of the brain increased 
markedly with the time of infusion. No significant changes in the other amino acids 
of the brain were found after the administration of ammonia. In contrast, when the 
glutamine in the brain was elevated by removal of the liver or alteration of the cir- 
culation to the liver, smaller but definite increases in other amino acids, such as 
phenylalanine and tyrosine were found in the brain. The typical electro-encephalo- 
gram during coma induced by intoxication with ammonia differs from that seen in 
coma of liverless animals and from the essentially normal recordings obtained 
during the coma of animals with Eck’s fistula.’ 
We have measured the total free amino acids in the brain, plasma, skeletal muscle 
and cardiac muscle of rats under a variety of conditions and have examined the 
relationship of the content of glutamine to the level of total free amino acids. The 
effect of administration of insulin on the amino acids and the effect of variations 
in body temperature have also been studied in normal rats, eviscerated rats, and 
eviscerated-adrenalectomized rats. 
EXPERIMENTAL METHODS AND MATERIAL 
Adult male rats of the Sprague-Dawley strain, weighing from 210 to 330g and 
maintained on Fromm’s dog food, were used in these studies. Hepatectomy was 
done by a two-stage evisceration. Ether anesthesia was used for both stages. In the 
first stage, the vena cava was ligated with surgical silk just above the kidneys and 
a cellophane band was placed around the portal vein so that adequate collateral 
circulation would be established. About 6 weeks later, the liver was removed with 
the stomach, intestines, spleen, and pancreas. Cystostomy with a small polyvinyl 
catheter in these and in control rats made continuous collection of urine possible. 
The adrenal glands were also removed from some of the rats at the time of eviscera- 
tion, and in some others I or 2 days prior to evisceration. 
A continuous intravenous infusion was administered at the rate of 1.25 ml/h 
to each rat. It contained physiologic saline solution, penicillin and streptomycin in 
sufficient quantities so that 1000 units of penicillin and 5 mg of streptomycin were 
given per 24h. Insulin when used and glucose were also given in the continuous 
infusion. The dose of insulin was 4 units/24 h and it was given to some of the rats 
who were receiving glucose at the rate of 44-125 mg/1o0o g of rat per h. Other rats 
References p. 460 
