Additive Effects of Hypothermia and Phenobarbitol upon Cerebral Oxygen Consumption in the Rat

Abstract

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.

No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia

“…10,48 Although we did not currently measure cerebral oxygen or glucose consumption, their inhibition can be assumed. In view of the coupling of CBF and metabolism, and as shown in many other studies, 22 it appears that the effects of barbiturates and hypothermia on cerebrometabolic rates are additive. 31,47,49,71 Barbiturates decrease blood flow by exerting a direct constrictive effect on cerebral arteries.…”

“…5 However, it is unknown whether barbiturate medications provide additional neuroprotection under hypothermic conditions. It has been shown that additional administration of barbiturates leads to a further reduction in the CMRO 2 and the cerebral metabolic rate of glucose; 22,31,49,71 however, it has not yet been confirmed that these additional reductions result in additional neuroprotection. 38 We conducted this study to investigate whether administration of barbiturates in burst-suppressive doses increases the protective efficacy of induced mild hypothermia.…”

Effect of Long-Term Mild Hypothermia or Short-Term Mild Hypothermia on Outcome of Patients with Severe Traumatic Brain Injury

“…It is believed that the beneficial effects of mild to moderate hypothermia act via metabolic and biochemical processes. Such mechanisms include temperature-dependent reduction of CMRO2, decrease of free radical production (Hagerdal, 1979;Hayashi et al, 1997;Vink et al, 1987), limitation of BBB disruption (Jiang et al, 1992;Smith and Hall, 1996) and brain edema (Shiozaki et al, 1993) attenuation of ionic disruption (Welsh et al, 1990), and decrease of excitatory amino-acid releases (Busto et al, 1989;Mitani and Kataoka, 1991b), reduction of cerebral lactate accumulation (Jiang et al, 2004), shunt of an increased fraction of glucose metabolism (Kaibara et al, 1999), inhibition of excessive calcium neuronal entry and intracellular calcium overload (Mitani and Kataoka, 1991a).…”

Hypothermia and thiopentone sodium: Individual and combined neuroprotective effects on cortical cultures exposed to prolonged hypoxic episodes

“…It is understandable here that the protective effect of combined application of hypothermia and TPS on ischemic neurons is not simply additive, as postulated by Lafferty et al (1978) and Hagerdal et al (1979). There is considerable variation in the magnitude of neuroprotection of hypothermia and TPS combinations in relation to the degree of ischemic insults.…”

“…There is considerable controversy concerning neuroprotection that pertains to the degree of hypothermic temperatures (McDonald et al, 1991; Clifton et al, 2001), dosage of barbiturates (Warner et al; 1996; Shibuta et al, 1998), and dosage regime with combined application of hypothermia and barbiturates (Hagerdal et al, 1979; Steen et al, 1983). However, no reports on culture studies have compared these aspects in detail.…”