title: Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.
abstract: Tourniquet-imposed ischemia-reperfusion of extremities generates reactive oxygen and nitrogen species (RONS), which can disrupt intermediary metabolism and ATP production. This study tested the hypothesis that fluid resuscitation with pyruvate, a natural antioxidant and metabolic fuel, ameliorates the deleterious effects of ischemia-reperfusion on intermediary metabolism in skeletal muscle. Anesthetized male goats (∼25 kg) were bled to a mean arterial pressure of 48 ± 1 mmHg and then subjected to 90 min hindlimb ischemia with a tourniquet and femoral crossclamp, followed by 4-h reperfusion. Lactated Ringers (LR) or pyruvate Ringers (PR) was infused intravenous for 90 min, from 30 min ischemia to 30 min reperfusion, to deliver 0.05 mmol kg(-1) min(-1) lactate or pyruvate. Time controls (TC) underwent neither hemorrhage nor hindlimb ischemia. Lipid peroxidation product 8-isoprostane, RONS-sensitive aconitase and creatine kinase activities, antioxidant superoxide dismutase activity, and phosphocreatine phosphorylation potential ([PCr]/[{Cr}{P(i)}]), an index of tissue energy state, were measured in reperfused gastrocnemius at 90 min resuscitation (n = 6 all groups) and 3.5 h post-resuscitation (n = 8 TC, 9 LR, 10 PR). PR more effectively than LR suppressed 8-isoprostane formation, prevented inactivation of aconitase and creatine kinase, doubled superoxide dismutase activity, and augmented [PCr]/([Cr][P(i)]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.
authors.affiliation: Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Hunaid A
authors.initials: HA
authors.lastname: Gurji
authors.forename: Daniel W
authors.initials: DW
authors.lastname: White
authors.forename: Besim
authors.initials: B
authors.lastname: Hoxha
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Harbor
authors.forename: Diana R
authors.initials: DR
authors.lastname: Schulz
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Williams
authors.forename: Albert H
authors.initials: AH
authors.lastname: Olivencia-Yurvati
authors.forename: Robert T
authors.initials: RT
authors.lastname: Mallet
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D019343:Citric Acid / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D006041:Goats; D020896:Hypovolemia / Q000188:drug therapy* / Q000378:metabolism; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy*; D014111:Tourniquets / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D019343:Citric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; D015237:Dinoprost
keywords: 8-isoprostane; Creatine kinase; hypovolemia; phosphorylation potential