Mild and Moderate Hypothermia (α-Stat) Do Not Impair the Coupling Between Local Cerebral Blood Flow and Metabolism in Rats

Abstract

Background and Purpose-The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). Methods-Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO 2 (␣-stat). Pericranial temperature was maintained normothermic (37.5°C, nϭ12) or was reduced to 35°C (nϭ12) or 32°C (nϭ12 35°C rϭ0.96, 32°C rϭ0.96, PϽ0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/mol during anesthesia (PϽ0.05), remained at 2.4 mL/mol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/mol, PϽ0.05). Conclusions-Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.

Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia studies in the rat: A comparative study

“…Dudley and colleagues (Dudley et al, 1982) reported that a 60mg/kg single dose of α-chloralose reduces the cerebral glucose utilization rate to 35−47% of that in the awake preparation in the cortex, and Nakao et al (2001) found thata 50mg/kg bolus followed by a 40 mg/kg/h maintenance dose reduced glucose utilization to 36% in the sensory motor cortex. These reductions in cerebral glucose metabolism in the cortex are very similar to the reductions observed with isoflurane at the concentrations used in the present study (Krafft et al, 2000;Ori et al, 1986). In addition, the α-chloralose dosing used (60 mg/kg bolus; 30 mg/kg/hr maintenance) is in line with the average dosing used in a variety of functional activation studies (64±15 mg/kg; 34±10 mg/kg/hr).…”

Acid–base management – is it relevant for the study design of hypothermic neuroprotection?

“…3) Table 3. Local cerebral blood flow of the experimental groups (with permission from [16,17] between local CBF and local cerebral glucose utilization was preserved but was shifted to a higher level (Fig. 3) (P < 0.05).…”

“…Table 1. Physiological variables of the experimental groups (with permission from [16,17] [16,17] [16,17]). …”

“…Local cerebral blood flow was measured in 41 different brain structures ( Table 2. Local cerebral glucose utilization of the experimental groups (with permission from [16,17] found during mild hypothermia in all structures except for three (cochlear nuclei, hippocampus CA1, and parietal cortex). Compared to pH-stat management, moderate hypothermia using a -stat management was associated with a decrease in local CBF in all but five brain structures (cochlear nuclei, dentate nuclei, superior olive, internal capsule, medial habenulae).…”

“…It became evident that local CBF/metabolism coupling is well preserved during hypothermia down to at least 32°C -managed by pH-stat [16] -as well as its management by a -stat [17]. To emphasize the effect of acid-base management on CBF and brain metabolism under physiological conditions, pH-stat and a -stat data of the two latter studies were combined and compared.…”