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 electrophys...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.展开更多
基金Supported by Grant#W911NF0910086 from the United States Department of DefensePredoctoral fellowships from the Graduate School of Biomedical Sciences,University of North Texas Health Science Center to Gurji HA and White DW
文摘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.
