Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 239, Issue 2, Pages 240-249Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370213514329
Keywords
Creatine kinase; hypovolemia; 8-isoprostane; phosphorylation potential
Categories
Funding
- United States Department of Defense [W911NF0910086]
- National Institute of Neurological Disorders and Stroke [NS076865]
- Graduate School of Biomedical Sciences, University of North Texas Health Science Center
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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 (similar to 25 kg) were bled to a mean arterial pressure of 48 +/- 1 mm Hg 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 tour-niqueted muscle.
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