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The effect of arterial hypotension on cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PGr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) was studied in male Wistar rats with unilateral carotid ligation exposed to arterial by hypoxia (PaO2 25 torr) for 20 min. while the body temperature was maintained at 32 degrees C and 27 degrees C. Brain metabolite levels were normal in normotensive hypothermic animals exposed to hypoxia, but reduction in arterial pressure to 75 torr caused a significant (p less than 0.05) decrease in ATP and PCr values and a significant increase in lactate and NADH levels. These changes were comparable to those of normothermic normotensive, hypoxic animals. Furthermore, there was no significant differences in the brain metabolite levels between the two hypotensive hypoxic groups. These results indicate that arterial hypotension severely alters the cerebral protective effect of hypothermia against injury caused by hypoxia, and that further reduction in body temperature (from 32 degrees C to 27 degrees C) will not prevent the harmful effect of hypoxia upon the brain in hypotensive rats.

Male Wistar rats with unilateral carotid ligation were exposed to arterial hypoxia (PaO2 20-23 torr for 20 min) while body temperature was controlled at 37 degrees C, 36 degrees C, or 34 degrees C. Brain cortical concentrations of ATP, phosphocreatine (PCr) and lactate were measured microfluorometrically. Normothermic hypoxic rats had severe metabolic changes with low brain ATP and extremely high brain lactate. When rectal temperature was controlled at 36 degrees C during hypoxia, brain ATP was not different from that observed in normothermic, normoxic rats, and brain lactate was significantly lower than during normothermic hypoxia. At 34 degrees C, brain lactate was even less, but still three times higher than that observed in normothermic normoxic rats. PCr was significantly higher following hypoxia at 34 degrees C than at 37 degrees C. In part, this latter finding may reflect preservation of intracellular pH at 34 degrees C. A decrease of body temperature of 1-3 degrees C can minimize or prevent brain energy failure during hypoxia as well as decrease the magnitude of brain tissue acidosis. Thus, in experiments examining "cerebral protective effects" of therapies during brain hypoxia-ischemia, stringent control of body temperature is necessary. Furthermore, a possible clinical benefit resulting from modest reduction in body temperature in patients with marginal cerebral oxygenation is suggested.

In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.

The quantitative effects of a combination of hypothermia and phenobarbital on cerebral oxygen uptake (CMRo2) was studied in rats, curarized and artificially ventilated with 70% nitrous oxide in oxygen. Cerebral blood flow (CBF) was measured with a modification of the KETY & SCHMIDT (1948) technique, using 133xenon as a tracer. Arteriovenous difference in oxygen content over the brain was measured and CMRo2 was calculated. Four groups were studied. Group 1 was a control group. The three experimental groups were injected with phenobarbital intraperitoneally: Group 2 with 50 mg/kg body weight; Group 3 with 150 mg/kg; and Group 4 with 50 mg/kg of phenobarbital, and, in addition, body temperature was lowered to 32 degrees C in this group. CMRo2 in groups 2, 3 and 4 was reduced by 22, 37 and 43%, respectively, compared to Group 1. The changes in CBF were of the same magnitude. In a previous study we have found that CMRo2 decreases by 5% per 1 degree C decrease in body temperature. The value for CMRo2 in Group 4 is close to the value obtained if the effect of 50 mg/kg body weight of phenobarbital on CMRo2 is added to the effect of a temperature reduction of 5 degrees C. It is concluded that the effects of barbiturates and hypothermia on CMRo2 are additive.