Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation.
Pyruvate-enriched cardioplegia suppresses cardiopulmonary bypass-induced myocardial inflammation.
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富含丙酮酸的心麻痹液可抑制体外循环引起的心肌炎症。
DOI：
10.1016/j.athoracsur.2010.06.010
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Mallet,RobertT
中科院分区：
文献类型：
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作者：
Ryou,Myoung-Gwi;Flaherty,DevinC;Hoxha,Besim;Gurji,Hunaid;Sun,Jie;Hodge,LisaM;Olivencia-Yurvati,AlbertH;Mallet,RobertT
心脏旁路诱导的氧化应激引发炎症，可损伤心肌。本研究测试了富含中间代谢物和抗氧化剂丙酮酸盐的心脏停搏液是否能抑制转流后心肌炎症.METHODSPigs在体外循环中维持，同时他们的心脏用4：1的血液：晶体心脏停搏液停搏60分钟，其中晶体含有188 mM葡萄糖± 24 mM丙酮酸盐。全血再灌注30分钟后，猪从旁路中断奶，恢复4小时。测定冠状窦血浆谷胱甘肽（GSH）和谷胱甘肽二硫化物（GSSG），间接监测心肌GSH氧化还原状态（GSH/GSSG）。体外循环后4 h取左室心肌，测定C反应蛋白、基质金属蛋白酶2和9及金属蛋白酶组织抑制剂2（TIMP-2），并通过组织学和髓过氧化物酶测定评估中性粒细胞浸润。但丙酮酸心脏停搏液使冠状窦GSH/GSSG显著升高，并持续4小时。心肌C-反应蛋白含量增加5.6倍后，控制旁路，中性粒细胞浸润和髓过氧化物酶活性也增加，但磷酸盐强化心脏停搏液防止这些炎症反应。与非旁路假手术值相比，对照心脏停搏液降低心肌TIMP-2含量59%，增加基质金属蛋白酶-9活性35%，但丙酮酸盐心脏停搏液使TIMP-2含量增加9倍，并阻止基质金属蛋白酶-9的增加。基质金属蛋白酶-2不受旁路±丙酮酸盐的影响。结论丙酮酸盐心脏停搏液可抑制体外循环诱导的心肌炎症。GSH/GSSG和TIMP-2的增加可能介导丙酮酸的作用。
BACKGROUNDCardiopulmonary bypass-induced oxidative stress initiates inflammation that can damage the myocardium. This study tested whether cardioplegia enriched with the intermediary metabolite and antioxidant pyruvate dampens postbypass myocardial inflammation.METHODSPigs were maintained on cardiopulmonary bypass while their hearts were arrested for 60 minutes with 4:1 blood:crystalloid cardioplegia, in which the crystalloid contained 188 mM glucose ± 24 mM pyruvate. Pigs were weaned from bypass after 30 minutes of whole blood reperfusion and recovered for 4 hours. Glutathione (GSH) and glutathione disulfide (GSSG) were measured in coronary sinus plasma to indirectly monitor myocardial GSH redox state (GSH/GSSG). Left ventricular myocardium was sampled 4 hours after cardiopulmonary bypass for analyses of C-reactive protein, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinase-2 (TIMP-2), and to assess neutrophil infiltration by histology and myeloperoxidase assay.RESULTSCoronary sinus GSH/GSSG fell 70% after cardiopulmonary bypass with control cardioplegia, but pyruvate cardioplegia produced a robust increase in coronary sinus GSH/GSSG that persisted for 4 hours after bypass. Myocardial C-reactive protein content increased 5.6-fold after control bypass, and neutrophil infiltration and myeloperoxidase activity also increased, but pyruvate-fortified cardioplegia prevented these inflammatory effects. Control cardioplegia lowered myocardial TIMP-2 content by 59% and increased matrix metalloproteinase-9 activity by 35% versus nonbypass sham values, but pyruvate cardioplegia increased TIMP-2 content ninefold versus control cardioplegia and prevented the increase in matrix metalloproteinase-9. Matrix metalloproteinase-2 was not affected by bypass ± pyruvate.CONCLUSIONSPyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.