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Macaque monkeys acclimatized to a restraint chair were fitted with indwelling venous and urinary catheters. After basal rates of urine production and creatinine clearance were determined, a 50 mg dose of plasma dialysate albumin fraction obtained from the woodchuck was administered intravenously in a total volume of 2.5 ml. Plasma fractions were collected during the winter interval of hibernation (hibernation "trigger" or HT), or during the summer active (SAWA) period. Although the SAWA fraction exerted no effects on renal function, HT caused a significant reduction in creatinine clearance. In addition, a tendency toward reduced urine flow and creatinine production occurred following the HT infusion. These findings suggest that over and above the hypothermia, aphagia and opioid-like behavioral depression induced by HT, the albumin fraction (HT) present endogenously in the woodchuck during winter torpor, exerts a direct action on the kidney of the primate, possibly on the mechanisms underlying glomerular filtration and the tubular reabsorption process.

In ovariectomized adult female macaque monkeys, cannulae were affixed bilaterally to the skull for intracerbroventricular injection. Baseline temperature, heart rate, food and water intakes were monitored in each animal after it had been acclimatized to a primate restraining chair. Lyophilized serum albumin fractions extracted from the blood of hibernating woodchucks or summer active, nonhibernating woodchucks were reconstituted in an artificial CSF. Following the intracerebroventricular injection of 3.0 to 4.0 mg of hibernating woodchuck albumin (HWA) in a volume of 300 to 400 microliters, a decline in the temperature of the monkey occurred which varied in magnitude and duration. A marked inhibition of food intake, accompanied by a decline in prandial water intake, persisted for 24 to 36 hours. This hypophagia was due mainly to a reduction in the number of feeding episodes during the periods of observation. Although heart rate declined intermittently, respiratory rates remained unchanged. Summer active woodchuck albumin (SAWA) or bovine serum albumin (BSA) given in the identical range of doses, as well as artificial CSF, exerted little or no effect either on body temperature of the primate or on its food intake. These results demonstrate for the first time that a plasma "trigger" factor, obtained from a hibernating animal in torpor, exerts a direct physiological action on the brain of a mammal which is incapable of entering into hibernation. Vital metabolic, thermoregulatory and other control processes mediated by diencephalic and other systems in the CNS are directly suppressed by the "trigger" factor. The clinical implications of these findings are presented.

1. Characterization of fetal, winter-hibernating, winter-active, summer-active and summer-induced hibernating hemoglobins of 13-lined ground squirrels (Citellus tridecemlineatus) by isoelectric focusing (IEF) pH 7.0-9.0 indicated that this molecule is extremely responsive to the various activity states of this hibernator. 2. Major alterations of ground squirrel hemoglobin occur with the varying activity states as evidenced by the distinctive changes in the isoelectric points (pIs) of these protein components. 3. Hemoglobin from winter-hibernating or summer-induced hibernating ground squirrels does not revert to a fetal type of hemoglobin. 4. The presence of an additional hemoglobin peak pI 6.55 in the summer-induced hibernator may serve as a possible assay for hibernation inducing trigger(s) (HIT) molecules under study in our laboratory.