TY - JOUR
T1 - Pyruvate-enriched resuscitation
T2 - Metabolic support of post-ischemic hindlimb muscle in hypovolemic goats
AU - Gurji, Hunaid A.
AU - White, Daniel W.
AU - Hoxha, Besim
AU - Sun, Jie
AU - Harbor, Jessica P.
AU - Schulz, Diana R.
AU - Williams, Arthur G.
AU - Olivencia-Yurvati, Albert H.
AU - Mallet, Robert T.
N1 - Funding Information:
The outstanding technical support of Shirley Nelson, R.L.A.T. is gratefully acknowledged. This study was conducted in partial fulfillment of the requirements for the PhD degree for HAG. This work was supported by research grants #W911NF0910086 from the United States Department of Defense and NS076865 from the National Institute of Neurological Disorders and Stroke. HAG and DWW were supported by predoctoral fellowships from the Graduate School of Biomedical Sciences, University of North Texas Health Science Center. This work was completed by HAG in partial fulfillment of the requirements for the PhD degree at University of North Texas Health Science Center.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - 8-isoprostane
KW - Creatine kinase
KW - hypovolemia
KW - phosphorylation potential
UR - http://www.scopus.com/inward/record.url?scp=84893972059&partnerID=8YFLogxK
U2 - 10.1177/1535370213514329
DO - 10.1177/1535370213514329
M3 - Article
C2 - 24414481
AN - SCOPUS:84893972059
VL - 239
SP - 240
EP - 249
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 1535-3702
IS - 2
ER -