Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.
Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.
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DOI：
10.5492/wjccm.v2.i4.56
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发表时间：
2013-11-04
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影响因子：
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通讯作者：
Mallet, Robert T
中科院分区：
文献类型：
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作者：
Gurji, Hunaid A;White, Daniel W;Mallet, Robert T
目的：验证富含生理抗氧化剂和能量底物丙酮酸(PR)的林格液在低血容量和后肢缺血再灌流时对心肌代谢和电生理功能的保护作用优于乳酸林格液(LR)的假说。采用止血带加股动脉夹闭造成大鼠右后肢缺血90min。从后肢缺血30min至缺血30min，分别静注乳酸L或丙酮酸0.05mmoL/kg。时间对照组(TC)既没有出血、后肢缺血，也没有复苏。分别于复苏后90min(每组6只)和3.5h后(LR组9只，PR组10只，TC组8只)处死山羊，取左室心肌组织。结果：复苏后90min和3.5h，心肌8-异前列腺素含量、磷酸肌酸磷酸化潜能、肌酸激酶活性和心率调整QT间期(QTC)变异性均得到评价。PR较LR显著降低心律失常前QTC变异性(P<；0.05)；这种效应在复苏后3.5小时持续存在。复苏后3h和3.5h，PR使心肌氧化应激产物8-异前列腺素含量分别降低39%和37%。肌酸激酶活性在LR术后较TC下降42%(P<；0.05)，但PR后稳定(P<；0.02 vs LR后)。与TC和LR相比，PR增加了磷酸肌酸磷酸化潜能(衡量ATP自由能状态)(P<；0.05)；这种能量增强持续到复苏后3.5h。结论：富含丙酮酸的复苏通过增强心肌能量状态和保护肌酸激酶活性，稳定了中枢性低血容量和后肢缺血再灌注时的心电功能。
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, pyruvate-enriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemia-reperfusion.