Prolonged anoxic survival due to anoxia pre-exposure: brain ATP, lactate, and pyruvate

Abstract

Rats subjected to a brief anoxia can survive go sec in a second anoxia, compared to a 60-sec survival time of control animals. Slower disappearance of ATP concentration in the brain during the second exposure indicates this longer survival is due to an altered cerebral energy metabolism. Initial cerebral ATP concentration is no higher in pre-exposed animals than in controls. When glycolysis is inhibited by iodoacetate before testing in anoxia, the advantage of pre-exposure disappears, suggesting the longer survival may be due to increased anacrobic glycolysis. Lactate accumulates faster during anoxia in the brains of pre-exposed animals than in controls, suggesting that increased anaerobic glycolysis is the cause of the prolonged survival. This effect is not due to increased cerebral glucose concentration. A possible reason for this increased glycolysis, and thus the prolonged survival, could be an increase of a compound, such as pyruvate, capable of oxidizing NADH. The initial pyruvate is higher in pre-exposed animals than in controls and injection of pyruvate increases the survival time slightly.

Studies on the Intracerebral Toxicity of Ammonia*

“…Furthermore, ammonia metabolism in brain appears to be compartmented (36), and current methods cannot assess any differences in energy metabolism within individual cerebral pools of varying size. In spite of these qualifications, in the one available study wherein neurologic findings were compared with acute cerebral ATP changes in anoxic rats, a one-third depletion in brain ATP was associated with death (37). Furthermore, delay of the cerebral ATP decrease by conditioning to anoxia delayed the onset of death in anoxic rats until the brain ATP fell again by about one-third from normal (37), and decreased ATP utilization by hypothermia and anesthesia likewise protected the animals against the effects of anoxia (34).…”

“…In spite of these qualifications, in the one available study wherein neurologic findings were compared with acute cerebral ATP changes in anoxic rats, a one-third depletion in brain ATP was associated with death (37). Furthermore, delay of the cerebral ATP decrease by conditioning to anoxia delayed the onset of death in anoxic rats until the brain ATP fell again by about one-third from normal (37), and decreased ATP utilization by hypothermia and anesthesia likewise protected the animals against the effects of anoxia (34). The decrease in phosphocreatine before the development of drowsiness and the fall in ATP before onset of overt stupor suggest that these changes may have not only chronologically but also causally preceded the onset of ammonia-induced coma.…”

Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?

“…The first experimentations of hypoxic preconditioning targeting the brain were performed in the early 60 s. Dahl et al 5 showed that pre-exposure to hypoxia could prolong anoxic survival by preserving brain metabolism. In a study done by Schurr et al, 6 rat hippocampal slices were exposed to a short 5-min anoxia period; 30 min thereafter, the slices were challenged by a longer period of anoxia (10 min).…”

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase

“…This neuroprotection is believed to occur through complex signal transduction pathways involving the activations of adenosine receptors [8,9] , protein kinase C [10][11][12][13] and mitochondrial adenosine triphosphate-regulated potassium (K ATP ) channels [2,14] . Interestingly, the effect of ischemic preconditioning (IPC) of brain [15,16] was demonstrated before that of heart IPC [17] . Brain and heart share common signal transduction pathways, including activation of K ATP channel [18,19] .…”