Pyruvate improves cerebral metabolism during hemorrhagic shock

Pyruvate (PYR) improves cellular and organ function hypoxia and ischemia by stabilizing the reduced nicotinamide adenine dinucleotide redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluate d the effects of intravenous pyruvate on neocortical function, indexes of t he cytosolic redox state, cellular energy state, and ischemia during a prol onged (4 h) controlled arterial hemorrhage (40 mmHg) in swine. Thirty minut es after the onset of hemorrhagic shock, sodium PYR (n = 8) was infused (0. 5 g.kg(-1).zh(-1)) to attain arterial levels of 5 mM. The volume and osmoti c effects were matched with 10% NaCl [hypertonic saline (HTS)] (n = 8) or 0 .9% NaCl [normal saline (NS)] (n = 8). During the hemorrhage protocol, the time to peak hemorrhage volume was significantly delayed in the PYR group c ompared with the HTS and NS groups (94 +/-5 vs. 73 +/-6 and 72 +/-4 min, P < 0.05). In addition to the early onset of the decompensatory phase of hemo rrhagic shock, the complete return of the hemorrhage volume during decompen satory shock resulted in the death of five and four animals, respectively, in the HTS and NS groups. In contrast, in the PYR group, reinfusion of the hemorrhage volume was slower and all animals survived the 4-h hemorrhage pr otocol. During hemorrhage, the PYR group also exhibited improved cerebral c ortical metabolic and function status. PYR slowed and reduced the rise in n eocortical microdialysis levels of adenosine, inosine, and hypoxanthine and delayed the loss of cerebral cortical biopsy ATP and phosphocreatine conte nt. This improvement in energetic status was evident in the improved preser vation of the electrocorticogram in the PYR group. PYR also prevented the e ightfold increase in the excitotoxic amino acid glutamate observed in the H TS group. The findings show that PYR administered after the onset of hemorr hagic shock markedly improves cerebral metabolic and functional status for at least 4 h.