Intravenous pyruvate prolongs survival during hemorrhagic shock in swine

Pyruvate improves cellular and organ function during hypoxia and ischemia a nd stabilizes the NADH redox state and cytosolic ATP phosphorylation potent ial. In this in vivo study, we evaluated the effects of intravenous pyruvat e on cardiovascular and neocortical function, indexes of the cytosolic redo x state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during c ontrolled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Naf pyruv ate was infused 1 h before (1 g.kg(-1).h(-1)) and 2 h during (0.5 g.kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovas cular decompensation between 60 and 90 min, with an average time until deat h of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruva te group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvat e group had better cardiovascular and cerebrovascular function with signifi cantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyr uvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevent ed the net efflux of ADO + HX + Ino into the sagittal sinus. The findings r eveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.