The Effect of Profound Levels of Hypothermia (Below 14°C) on Canine Cerebral Metabolism

Abstract

Summary: The goal of this study was to determine the temperature coefficient (QIO) for canine CMR02 at tem peratures below 14°C. Eight dogs were anesthetized with halothane for surgical preparation. The animals were placed on total cardiopulmonary bypass and CBF was measured by direct sagittal sinus outflow. Duplicate mea surements were taken at 37, 13, and 7°C. The EEG be came isoelectric at a temperature of 12.0 ± 0.8°C. The QIO between 13 and 7°C was 2.19 ± 0.59. With rewarming to 37°C, cerebral metabolic variables returned to control It is commonly assumed that the basis for hypo thermia-induced cerebral protection is metabolic suppression. If one assumes that the temperature coefficient (QIO ) for CMR02 is similar to that for most biologic reaction rates of between 2.0 and 3.0 (Harper, 1973), the magnitude of protection clini cally observed at 15-18°C (Tharion et aI., 1982) ex ceeds that which would be predicted on a metabolic basis alone.In two previous studies we examined the effect of temperature on canine CMR02 over the tempera ture range of 14-37°C and demonstrated that the relationship is a complex one, resulting from the combined direct effect of temperature on biologic reaction rates and the effect this has on cerebral function as reflected by the EEG (Steen et aI., 1983;Michenfelder and Milde, 1991 877 levels. Brain biopsies taken at the end of the study yielded normal values for brain energy stores. We con clude that the QIO for CMR02 at temperatures between 7 and 37"C can be profoundly affected by the state of cere bral function as reflected by the EEG. In the absence of EEG activity, an expected QIO value of 2.2 reflects only the direct effect of temperature on the rates of biologic reactions. Key Words: Cerebral blood flow-Cerebral metabolic rate for oxygen-Cerebral protection Hypothermia.progresses from a near normal pattern to an isoelec tric one. Such a Q10 would fully explain the proven brain protection at 15-18°C.The present study was pursued to test the hy pothesis that the CMR02 effects of hypothermia re vert to a simple exponential relationship at and be low temperatures associated with an isoelectric EEG (below 14°C), resulting in a Q,o value of near 2.0. We are unaware of any other reports concerned with cerebral metabolic rates at temperatures below 14°C. METHODSThe protocol was reviewed and approved by the insti tutional animal care and use committee. Eight unmedi cated, fasting adult mongrel dogs, weighing 17.5 ± 2.2 kg (mean ± SD), were studied. Dogs were anesthetized with halothane 3-4% inspired followed by muscle paralysis with pancuronium 0.2 mg kg -I i. v. and intubation of the trachea. Ventilation was controlled to maintain P ac02 at 35-40 mm Hg. Anesthesia was maintained with halothane 1% (end-expired) in nitrogen and oxygen which were ad justed to maintain Pa02 at 100--150 mm Hg.The preparation of the animals for the study was iden tical to that previously described in detail (Michenfelder and Milde, 1991). In brief, CBF was measured by a sag ittal sinus outflow method (Mic...

Limitations of Mild, Moderate, and Profound Hypothermia in Protecting Developing Hippocampal Neurons After Simulated Ischemia

“…At deeper hypothermic temperatures (4°C), extensive damage was seen after 8 hours. It is unsurprising that such deep temperatures would cause damage so quickly; Michenfelder noted changes in electrical activity in canines starting at 27°C, with loss of signal occurring at *12°C (Michenfelder and Milde, 1992). This is a new finding for moderate and profound hypothermia and is consistent with our previously published work identifying neuron-specific injury after ultra-profound hypothermia, involving cooling and rewarming to 4°C .…”

Effect of extracorporeal life support on cerebral blood flow, metabolism and electrophysiology in normothermic cats

“…Our experimental model was designed to mimic the presence of complete cardiopulmonary failure as the worst possible case for the application of ECLS. In the literature only few experimental investigations have been reported that describe the effects of total bypass ECLS on cerebral metabolism and electrophysiology, which reflects the difficulty of establishing total bypass in small animals [17,18]. Our study of 2 h normothermic ECLS in cats revealed that brain tissues and plasma lactate substantially increased although blood pressure was maintained close to normal.…”

Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord

“…The first assumes that ischemic injury occurs secondary to depletion of metabolic stores and that hypothermia preserves these stores by reducing cerebral metabolic rate of oxygen consumption (CMRO 2 ). In animal models of cerebral ischemia, CMRO 2 declines monotonically by ϳ4.5% per degree over the range of 37-38°C (normothermia) to 15-18°C (profound hypothermia) (Michenfelder and Milde, 1992). These findings are clinically relevant, because recovery of normal function in humans can be observed after 60 min of circulatory arrest when the arrest occurs at 15-18°C (Tharion et al, 1982).…”