Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization
Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization
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DOI：
10.1093/eurheartj/ehi751
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发表时间：
2006-04-01
影响因子：
39.3
通讯作者：
Heusch, G
中科院分区：
文献类型：
--
作者：
Canton, M;Skyschally, A;Heusch, G
目的探讨冠状动脉微栓塞后心肌功能障碍的潜在机制。方法和结果麻醉猪冠状动脉内灌注微球。6小时后，微栓塞区（MEA）收缩壁增厚降低至基线的38 +/- 7%，原肌球蛋白中二硫交叉桥（DCB）的形成比偏远地区增加2.62 +/- 0.40倍。收缩功能损伤与DCB形成呈负相关（r=-0.68； P=0.015），并与tnf - α含量升高相关。DCB的形成反映在原肌球蛋白免疫反应性的增加，并在体外被二硫苏糖醇消除。抗坏血酸防止收缩功能障碍，并增加DCB和tnf - α。麻醉犬冠状动脉内微球输注8 h后，收缩功能降至基线的8 +/- 10%，MEA的DCB比边远地区高1.48 +/- 0.12。在意识清醒的狗，冠状动脉内微球输注6天后，心肌功能恢复到基线，DCB在远程和MEA之间不再有差异。收缩函数与DCB形成呈负相关（r=-0.83； P=0.005）。结论心肌纤维蛋白氧化可能是冠状动脉微栓塞后炎症与收缩功能障碍之间的机制联系。
Aims We addressed a potential mechanism of myocardial dysfunction following coronary microembolization at the level of myofibrillar proteins.Methods and results Anaesthetized pigs underwent intracoronary infusion of microspheres. After 6 h, the microembolized areas (MEA) had decreased systolic wall thickening to 38 +/- 7% of baseline and a 2.62 +/- 0.40-fold increase in the formation of disulphide cross-bridges (DCB) in tropomyosin relative to that in remote areas. The impairment in contractile function correlated inversely with DCB formation (r=-0.68; P=0.015) and was associated with increased TNF-alpha content. DCB formation was reflected by increased tropomyosin immunoreactivity and abolished in vitro by dithiothreitol. Ascorbic acid prevented contractile dysfunction as well as increased DCB and TNF-alpha. In anaesthetized dogs, 8 h after intracoronary microspheres infusion, contractile function was reduced to 8 +/- 10% of baseline and DCB in MEA was 1.48 +/- 0.12 higher than that in remote areas. In conscious dogs, 6 days after intracoronary microspheres infusion, myocardial function had returned to baseline and DCB was no longer different between remote and MEA. Again contractile function correlated inversely with DCB formation (r=-0.83; P=0.005).Conclusion Myofibrillar protein oxidation may represent a mechanistic link between inflammation and contractile dysfunction following coronary microembolization.