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

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 mmHg.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)variability 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.