QUANTITATIVE RELATIONSHIP BETWEEN BRAIN TEMPERATURE AND ENERGY-UTILIZATION RATE MEASURED IN-VIVO USING P-31 AND H-1 MAGNETIC-RESONANCE SPECTROSCOPY

In neonatal and adult animals, modest reduction in brain temperature ( 2-3 degrees C) during ischemia and hypoxia-ischemia provides partial o r complete neuroprotection. One potential mechanism for this effect is a decrease in brain energy utilization rate with consequent preservat ion of brain ATP, as occurs with profound hypothermia, To determine th e extent to which modest hypothermia is associated with a decrease in brain energy utilization rate, in vivo P-31 and H-1 magnetic resonance spectroscopy (MRS) was used to measure the rate of change in brain co ncentration of phosphocreatine, nucleoside triphosphate, and lactate a fter complete ischemia induced by cardiac arrest in 11 piglets (8-16 d ). Preischemia metabolite concentrations and MRS-determined rate const ants were used to calculate the initial flux of high energy phosphate equivalents (d[similar to P]/dt, brain energy utilization rate). Basel ine physiologic and MRS measurements were obtained at 38.2 degrees C a nd repeated after brain temperature was adjusted between 28 and 41 deg rees C. This was followed by measurement of d[similar to P]/dt during complete ischemia at 1-2 degrees C increments within this temperature range, Adjusting brain temperature did not alter any systemic variable except for heart rate which directly correlated with brain temperatur e (r = 0.95, p < 0.001). Before ischemia brain temperature inversely c orrelated with phosphocreatine (r = -0.89, p < 0.001), and reflected c hanges in the phosphocreatine-ATP equilibrium, because brain temperatu re inversely correlated with intracellular pH (r = -0.77, p = 0.005). Brain temperature and d[similar to P]/dt were directly correlated and described by a linear relationship (slope = 0.61, intercept = -12, r = 0.92, p < 0.001). A reduction in brain temperature from normothermic values of 38.2 degrees C was associated with a decline in d[similar to P]/dt of 5.3% per 1 degrees C, and therefore decreases in d[similar t o P]/dt during modest hypothermia represent a potential mechanism cont ributing to neuroprotection.