The Metabolic Effects of Mild Hypothermia on Global Cerebral Ischemia and Recirculation in the Cat: Comparison to Normothermia and Hyperthermia

Abstract

Summary:The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8° ± OSC (n = 4), T = 32.1° ± 0.2°C (n = 5), and T = 34.6° ± 0.3°C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recircula tion. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31p nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of isch emia, no significant differences were detected in the re sponse of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooledThe effect of whole body hypothermia on cere bral metabolism has a long history (Field et aI., 1944). The possible beneficial effects of hypother mia on cerebral pathophysiological conditions have also been explored (see Siesj6, 1978). Whole body hypothermia, when applied judiciously, can curtail metabolic changes and lessen cerebral edema and neuropathologic damage associated with hypoxia (Carlsson et aI., 1976;Rosomoff 1959), and head injury (Shapiro et aI., 1974 141into one group, and the data compared to previously pub lished data from a normothermic group, T = 38.4° ± 0.6°C (n = 14), and a hyperthermic group, T = 40.6° ± 0.2°C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recircu lation, as well as a more rapid return of adenylate inten sities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of com plete global cerebral ischemia and recirculation. Key Words: 31p NMR spectroscopy-Cerebral ischemia Hypothermia-Body temperature, and cerebral ischemia. emia, including circulatory arrest, with recircula tion (Marshal et aI., 1956; Kramer et aI., 1968; Ber ing, 1974; Perna et aI., 1973; Wolin et aI., 1973;Hickey, 1985) and without recirculation (Stocker et aI., 1986); the isolated perfused brain (Norwood et aI., 1979); and focal cerebral ischemia (Simeone et aI., 1979;Rosomoff, 1957). These studies, which were performed at temperatures below 30°C, sug gest that hypothermia results in a reduction in the rate of degradation of brain energy metabolism dur ing the onset of hypothermic ischemia as well as a reduced level of brain tissue acidosis compared with normothermic ischemia. However, the clinical application of hypothermia is limited by adverse ef fects associated with level as well as the duration of hypothermia (Popovic, 1960;Michenfelder and Milde, 1977;Bjork and Hultquist, 1960; Brunberg et aI., 1974; Connolly et aI., 1962; Olesen et aI., 1971).

Quantitative Relationship between Brain Temperature and Energy Utilization Rate Measured in Vivo Using 31P AND 1H Magnetic Resonance Spectroscopy

“…temperature reductions of 4°C were associated with higher brain ATP concentration initially during ischemia, but by the end of the ischemic interval were similar to values of normothermic controls (8,9). In our laboratory, an intraischemic temperature difference of 2.9"C between normothermic and modestly hypothermic piglets was associated with a trend for greater preservation of brain ATP in cooler animals (57 versus 43% of control for hypothermic versus normothermic, p = 0.11) (4).…”

“…However, the effect of a modest reduction in temperature (2-3°C) on such variables has not been examined and cannot be extrapolated from these reports due to the absence of results at temperatures between 25 and 38°C. This issue is further clouded by the report of Chopp et al (8) in which the extent of change in phosphorylated metabolites during a fixed time interval of ischemia, as determined using 3 1~ MRS in adult cats, was independent of temperature over the range of 26.8-34.6"C. What has been examined is the effect of temperature on brain metabolic rate, using CMRo, as an index of metabolic activity. All studies in neonates and adults agree that a reduction in core body or brain temperature is associated with a lowering of CMRo,, but the magnitude of reduction in CMRo, for a given decrease in temperature remains controversial.…”

Experimental neuroprotection in ischemic stroke: a concise review

“…Hypothermia can target more than one aspect of secondary brain injury, including oxygen consumption and metabolic demand, 15 enzymatic degradation, neurotransmitter uptake, 7 membrane stabilization, and reduction in intracellular acidosis. 32,55 In a small study, hypothermia post-middle cerebral artery (MCA) stroke has been shown to be tolerable, help control intracranial pressure, and possibly lead to better neurological outcomes.…”

Out‐of‐hospital cardiac arrest: studies on aetiology, treatment and outcome

“…A reduction of cerebral oxygen consumption has been proposed (Hegnauer et al 1954) and other multifactorial physical and chemical mechanisms during and after low-flow induced ischaemia have also been postulated (Hypothermia after Cardiac Arrest Study Group 2002). These include reduction of intracellular acidosis (Chopp et al 1989), reducing cerebral oedema and protection of lipoprotein membranes (Dempsey et al 1987), inhibition of biosynthesis and release of excitatory neurotransmitters (Busto et al 1989). ATP concentration in brain tissue has been shown to most consistently reflect biochemical activity among available biochemical indicators.…”