title: Intravenous pyruvate prolongs survival during hemorrhagic shock in swine.
abstract: Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate 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 cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.
authors.affiliation: Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. pmongan@usuhs.mil
authors.forename: P D
authors.initials: PD
authors.lastname: Mongan
authors.forename: J L
authors.initials: JL
authors.lastname: Fontana
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Bünger
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D007773:Lactates / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D013552:Swine
chemical_list: D007773:Lactates; D011773:Pyruvates; D010100:Oxygen