Knott E Marty, Ryou Myoung-Gwi, Sun Jie, Heymann Abraham, Sharma Arti B, Lei Yu, Baig Mirza, Mallet Robert T, Olivencia-Yurvati Albert H
Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1123-30. doi: 10.1152/ajpheart.00322.2005. Epub 2005 May 20.
Cardioplegic arrest for bypass surgery imposes global ischemia on the myocardium, which generates oxyradicals and depletes myocardial high-energy phosphates. The glycolytic metabolite pyruvate, but not its reduced congener lactate, increases phosphorylation potential and detoxifies oxyradicals in ischemic and postischemic myocardium. This study tested the hypothesis that pyruvate mitigates oxidative stress and preserves the energy state in cardioplegically arrested myocardium. In situ swine hearts were arrested for 60 min with a 4:1 mixture of blood and crystalloid cardioplegia solution containing 188 mM glucose alone (control) or with additional 23.8 mM lactate or 23.8 mM pyruvate and then reperfused for 3 min with cardioplegia-free blood. Glutathione (GSH), glutathione disulfide (GSSG), and energy metabolites [phosphocreatine (PCr), creatine (Cr), P(i)] were measured in myocardium, which was snap frozen at 45 min arrest and 3 min reperfusion to determine antioxidant GSH redox state (GSH/GSSG) and PCr phosphorylation potential {[PCr]/([Cr][P(i)])}. Coronary sinus 8-isoprostane indexed oxidative stress. Pyruvate cardioplegia lowered 8-isoprostane release approximately 40% during arrest versus control and lactate cardioplegia. Lactate and pyruvate cardioplegia dampened (P < 0.05 vs. control) the surge of 8-isoprostane release following reperfusion. Pyruvate doubled GSH/GSSG versus lactate cardioplegia during arrest, but GSH/GSSG fell in all three groups after reperfusion. Myocardial [PCr]/([Cr][P(i)]) was maintained in all three groups during arrest. Pyruvate cardioplegia doubled [PCr]/([Cr][P(i)]) versus control and lactate cardioplegia after reperfusion. Pyruvate cardioplegia mitigates oxidative stress during cardioplegic arrest and enhances myocardial energy state on reperfusion.
心脏搭桥手术中的心脏停搏会使心肌遭受整体缺血，进而产生氧自由基并消耗心肌高能磷酸盐。糖酵解代谢产物丙酮酸，而非其还原产物乳酸，可增加磷酸化电位并使缺血及缺血后心肌中的氧自由基解毒。本研究检验了以下假设：丙酮酸可减轻氧化应激并维持心脏停搏心肌的能量状态。将猪的心脏原位用仅含188 mM葡萄糖的血液与晶体心脏停搏液按4:1混合（对照组）或额外添加23.8 mM乳酸或23.8 mM丙酮酸的混合液使其停搏60分钟，然后用无心脏停搏液的血液再灌注3分钟。在心脏停搏45分钟和再灌注3分钟时将心肌快速冷冻，测量心肌中的谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）和能量代谢产物[磷酸肌酸（PCr）、肌酸（Cr）、无机磷酸盐（P(i)）]，以确定抗氧化剂GSH氧化还原状态（GSH/GSSG）和PCr磷酸化电位{[PCr]/([Cr][P(i)])}。冠状窦8-异前列腺素可反映氧化应激。与对照组和乳酸心脏停搏液相比，丙酮酸心脏停搏液在心脏停搏期间使8-异前列腺素释放降低约40%。乳酸和丙酮酸心脏停搏液减轻了（与对照组相比P < 0.05）再灌注后8-异前列腺素释放的激增。在心脏停搏期间，与乳酸心脏停搏液相比，丙酮酸使GSH/GSSG增加了一倍，但再灌注后所有三组的GSH/GSSG均下降。在心脏停搏期间，所有三组的心肌[PCr]/([Cr][P(i)])均得以维持。再灌注后，与对照组和乳酸心脏停搏液相比，丙酮酸心脏停搏液使[PCr]/([Cr][P(i)])增加了一倍。丙酮酸心脏停搏液可减轻心脏停搏期间的氧化应激，并增强再灌注时的心肌能量状态。
