Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA.
Ann Thorac Surg. 2010 Nov;90(5):1529-35. doi: 10.1016/j.athoracsur.2010.06.010.
Cardiopulmonary 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.
Pigs 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.
Coronary 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.
Pyruvate-enriched cardioplegia dampens cardiopulmonary bypass-induced myocardial inflammation. Increased GSH/GSSG and TIMP-2 may mediate pyruvate's effects.
体外循环引起的氧化应激引发炎症，从而损害心肌。本研究旨在测试富含中间代谢产物和抗氧化剂丙酮酸盐的心脏停搏液是否能减轻体外循环后心肌炎症。
在心肺转流过程中，猪的心脏被停搏 60 分钟，使用血晶停搏液（4：1，其中晶体液含有 188mM 葡萄糖±24mM 丙酮酸盐）。在全血再灌注 30 分钟后，猪脱离心肺转流并恢复 4 小时。通过测量冠状窦血浆中的谷胱甘肽（GSH）和谷胱甘肽二硫化物（GSSG）来间接监测心肌 GSH 氧化还原状态（GSH/GSSG）。心肺转流 4 小时后，取左心室心肌样本进行 C 反应蛋白、基质金属蛋白酶 2 和 9 以及金属蛋白酶组织抑制剂-2（TIMP-2）分析，并通过组织学和髓过氧化物酶测定评估中性粒细胞浸润。
对照组心脏停搏液使心肺转流后冠状窦 GSH/GSSG 下降 70%，但丙酮酸盐心脏停搏液使冠状窦 GSH/GSSG 显著增加，并持续 4 小时。与非旁路假手术组相比，对照组旁路后心肌 C 反应蛋白含量增加 5.6 倍，中性粒细胞浸润和髓过氧化物酶活性也增加，但丙酮酸盐强化心脏停搏液可预防这些炎症反应。对照组心脏停搏液使心肌 TIMP-2 含量下降 59%，基质金属蛋白酶-9 活性增加 35%，而丙酮酸盐心脏停搏液使 TIMP-2 含量增加 9 倍，同时阻止了基质金属蛋白酶-9 的增加。基质金属蛋白酶-2 不受旁路±丙酮酸盐的影响。
富含丙酮酸盐的心脏停搏液可减轻体外循环引起的心肌炎症。增加的 GSH/GSSG 和 TIMP-2 可能介导了丙酮酸盐的作用。
