Protective Effects of Combinations of Hypothermia and Barbiturates in Cerebral Hypoxia in the Rat

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Abstract
The protective effects of phenobarbital and hypothermia in cerebral hypoxia were studied in Wistar rats with unilateral carotid ligation. The animals were exposed to hypoxia (PaO2 [arterial partial pressure for O2] 25-15 torr) for 25 min. Cerebral protection was evaluated by means of effects on cerebral tissue ATP, phosphocreatine (PCr), lactate, NADH values. At PaO2 25 torr, cerebral blood flow (CBF) and cerebral O2 consumption (CMRO2) were decreased by 25% either with phenobarbital, 50 mg/kg, or by hypothermia, 32.degree. C or decreased by 40-50% with hypothermia, 27.degree. C, phenobarbital, 150 mg/kg, or the combination of 32.degree. C and phenobarbital, 50 mg/kg. The group given phenobarbital, 50 mg/kg, as well as the normothermic hypoxic control group, had marked metabolic changes, with a 30-50% decrease in PCr and a 4- to 6-fold increase in lactate levels on the ligated side compared with the hypothermic rats. The hypothermic rats showed almost no metabolic sign of hypoxia. All rats in the group that received phenobarbital, 150 mg/kg, developed cardiac arrhythmias and decreases in blood pressure. No animal in this group survived. At PaO2 15 torr, hypothermia to 32.degree. C alone or combined with phenobarbital, 50 mg/kg, decreased PCr 40-50% and increased lactate values 4- to 5-fold on the ligated side compared with hypothermia to 27.degree. C alone. With the exception of an elevated lactate level on the ligated side, there was no metabolic sign of hypoxia with hypothermia to 27.degree. C. As judged by metabolic criteria, hypothermia offered better cerebral protection from hypoxia than did a dose of phenobarbital that gave the same decreases in CBF and CMRO2. Hypothermic rats had less severe metabolic acidosis and higher arterial O2 contents, which might partly explain the greater protective effect.