Changes of labile metabolites during anoxia in moderately hypo- and hyperthermic rats: correlation to membrane fluxes of K+.

The objective of this study was to assess the influence of temperature on the coupling among energy failure, depolarization, and ionic fluxes during anoxia. To that end, we induced anoxia by cardiac arrest in anesthetized rats maintained at a body temperature of either 34 degrees C or 40 degrees C, measured extracellular K+ concentration (K+e), and froze the neocortex through the exposed dura for measurements of phosphocreatine (PCr), creatine (Cr), ATP, ADP, and AMP, glucose, glycogen, pyruvate and lactate content after ischemic intervals of maximally 130 s. Free ADP (ADPf) concentrations were derived from the creatine kinase equilibrium. Hypothermia reduced the initial rate of rise in K+e, and delayed the terminal depolarization; however, both hypo- and hyperthermic animals showed massive loss of ion homeostasis at a K+e of 10-15 mM. The initial rate of rise in K+e did not correlate to changes in ATP, or ATP/ADPf ratio, suggesting that temperature changes per se may control the degree of activation of K+ conductances. The results clearly showed that, in both hyper- and hypothermic subjects, energy failure preceded the sudden activation of membrane conductances for ions. The results indicate that temperature primarily influences membrane permeability to ions like K+e (and Na+), and that cerebral energy state is secondarily affected. It is proposed that the higher rate of rise of K+e at high temperatures accelerates ATP hydrolysis primarily by enhancing metabolic rate in glial cells.