Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia  

作　　者：Hunaid A Gurji Daniel W White Besim Hoxha Jie Sun Albert H Olivencia-Yurvati Robert T Mallet 

机构地区：[1]Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States [2]Departments of Surgery, University of North Texas Health Science Center, Fort Worth, TX 76107, United States [3]Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, United States [4]Institute for Aging and Alzheimer’s Research, University of North Texas Health Science Center, Fort Worth, TX 76107, United States

出　　处：《World Journal of Critical Care Medicine》2013年第4期56-64,共9页世界重症医学杂志

基　　金：Supported by Grant#W911NF0910086 from the United States Department of Defense;Predoctoral fellowships from the Graduate School of Biomedical Sciences,University of North Texas Health Science Center to Gurji HA and White DW

摘　　要：AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate(PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's(LR) during hypovolemia and hindlimb ischemia-reperfusion.METHODS: Male domestic goats(25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mm Hg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls(TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation(n = 6 per group) or 3.5 h later(n = 9 LR, 10 PR, 8 TC).RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval(QTc) vari- ability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR(P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC(P < 0.05), but was stable post-PR(P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR(P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvateenriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemiareperfusion.AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate(PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's(LR) during hypovolemia and hindlimb ischemia-reperfusion.METHODS: Male domestic goats(25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mm Hg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls(TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation(n = 6 per group) or 3.5 h later(n = 9 LR, 10 PR, 8 TC).RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval(QTc) vari- ability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR(P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC(P < 0.05), but was stable post-PR(P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR(P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvateenriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemiareperfusion.

关 键 词：CREATINE kinase Electrocardiogram HYPOVOLEMIA 8-Isoprostane PHOSPHOCREATINE Reactive oxygen species Ringer’s LACTATE 

分 类 号：R33[医药卫生—人体生理学]