Pyruvate-enriched resuscitation: Metabolic support of post-ischemic hindlimb muscle in hypovolemic goats

Hunaid A. Gurji, Daniel W. White, Besim Hoxha, Jie Sun, Jessica P. Harbor, Diana R. Schulz, Arthur G. Williams, Albert H. Olivencia-Yurvati, Robert T. Mallet

Research output: Contribution to journalArticle

9 Scopus citations

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}{Pi}]), 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][Pi]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.

Original languageEnglish
Pages (from-to)240-249
Number of pages10
JournalExperimental Biology and Medicine
Volume239
Issue number2
DOIs
StatePublished - 1 Feb 2014

Keywords

  • 8-isoprostane
  • Creatine kinase
  • hypovolemia
  • phosphorylation potential

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