Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia
Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia
复制标题
DOI：
10.1161/circulationaha.106.684852
复制
发表时间：
2007-10-23
期刊：
影响因子：
37.8
通讯作者：
Becker, Bernhard F.
中科院分区：
文献类型：
--
作者：
Rehm, Markus;Bruegger, Dirk;Becker, Bernhard F.
背景-内皮糖萼的厚度惊人，可与微血管内皮细胞相媲美，这是近15年来发现的。正如已经证明的那样，这种结构在炎症和血管通透性的调节中起着关键作用。方法和结果-糖萼的两种组分，多配体蛋白聚糖-1和硫酸乙酰肝素，对18例体外循环升主动脉手术患者的动脉血进行了测定（n = 12例，n = 6例未进行深低温停循环）和14例接受肾下主动脉瘤手术的患者。患者的syndecan-1（1.2 μ g/dL）和硫酸乙酰肝素（590 μ g/dL）的基础值与对照组相似。麻醉和手术开始未引起变化。在再灌注早期（0 - 15分钟），伴有循环停止的全脑缺血（n = 12）之后，syndecan-1和硫酸乙酰肝素分别短暂增加42倍和10倍。心脏和肺局部缺血后（心肺转流术; n = 6），syndecan-1增加65倍，硫酸乙酰肝素增加19倍。肾缺血后分别增加15倍和3倍（n = 14）。缺血后早期升高呈正相关（r = 0.76，P < 0.001）。血浆细胞间粘附分子-1和血管细胞粘附分子-1的浓度没有变化。循环多形核粒细胞和缺血后硫酸乙酰肝素水平呈负相关。离体心脏（豚鼠）的免疫组织化学成像和免疫测定证实syndecan-1和硫酸乙酰肝素是释放到冠状静脉流出液中的内皮糖萼的组分。电子显微镜显示脱落的glycocalyx后缺血/reperfusion.Conclusions -这项研究提供了第一个证据，在人类脱落的内皮glycocalyx在缺血/再灌注程序。
Background - The astonishing thickness of the endothelial glycocalyx, which rivals that of endothelial cells in the microvasculature, was disclosed in the last 15 years. As already demonstrated, this structure plays a key role in the regulation of inflammation and vascular permeability.Methods and Results - Two components of the glycocalyx, syndecan-1 and heparan sulfate, were measured in arterial blood of 18 patients undergoing surgery of the ascending aorta with cardiopulmonary bypass ( n = 12 with and n = 6 without deep hypothermic circulatory arrest) and of 14 patients undergoing surgery for infrarenal aortic aneurysm. Basal values of syndecan-1 ( 1.2 mu g/dL) and heparan sulfate ( 590 mu g/dL) of patients were similar to those of control subjects. Anesthesia and initiation of surgery caused no changes. Global ischemia with circulatory arrest ( n = 12) was followed by transient 42- and 10-fold increases in syndecan-1 and heparan sulfate, respectively, during early reperfusion ( 0 to 15 minutes). After regional ischemia of heart and lungs ( cardiopulmonary bypass; n = 6), syndecan-1 increased 65-fold, and heparan sulfate increased 19-fold. Infrarenal ischemia was followed by 15- and 3-fold increases, respectively ( n = 14). The early postischemic rises were positively correlated ( r = 0.76, P < 0.001). Plasma concentrations of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 did not change. Circulating polymorphonuclear granulocytes and the level of postischemic heparan sulfate corresponded negatively. Immunohistochemical imaging and immunoassay of isolated hearts ( guinea pig) substantiated syndecan-1 and heparan sulfate as components of the endothelial glycocalyx released into the coronary venous effluent. Electron microscopy revealed shedding of the glycocalyx after ischemia/reperfusion.Conclusions - This study provides the first evidence in humans for shedding of the endothelial glycocalyx during ischemia/reperfusion procedures.