Jacob Matthias, Rehm Markus, Loetsch Michael, Paul Joern O, Bruegger Dirk, Welsch Ulrich, Conzen Peter, Becker Bernhard F
Clinic of Anesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany.
J Vasc Res. 2007;44(6):435-43. doi: 10.1159/000104871. Epub 2007 Jul 2.
Shear stress induces coronary dilatation via production of nitric oxide (NO). This should involve the endothelial glycocalyx (EG). A greater effect was expected of albumin versus hydroxyethyl starch (HES) perfusion, because albumin seals coronary leaks more effectively than HES in an EG-dependent way.
Isolated hearts (guinea pigs) were perfused at constant pressure with Krebs-Henseleit buffer augmented with 1/3 volume 5% human albumin or 6% HES (200/0.5 or 450/0.7). Coronary flow was also determined after EG digestion (heparinase) and with nitro-L-arginine (NO-L-Ag).
Coronary flow (9.50 +/- 1.09, 5.10 +/- 0.49, 4.87 +/- 1.19 and 4.15 +/- 0.09 ml/min/g for 'albumin', 'HES 200', 'HES 450' and 'control', respectively, n = 5-6) did not correlate with perfusate viscosity (0.83, 1.02, 1.24 and 0.77 cP, respectively). NO-L-Ag and heparinase diminished dilatation by albumin, but not additively. Alone NO-L-Ag suppressed coronary flow during infusion of HES 450. Electron microscopy revealed a coronary EG of 300 nm, reduced to 20 nm after heparinase. Cultured endothelial cells possessed an EG of 20 nm to begin with.
Albumin induces greater endothelial shear stress than HES, despite lower viscosity, provided the EG contains negative groups. HES 450 causes some NO-mediated dilatation via even a rudimentary EG. Cultured endothelial cells express only a rudimentary glycocalyx, limiting their usefulness as a model system.
剪切应力通过一氧化氮(NO)的产生诱导冠状动脉扩张。这应该涉及内皮糖萼(EG)。预期白蛋白灌注比羟乙基淀粉(HES)灌注有更大的效果,因为白蛋白以EG依赖的方式比HES更有效地封闭冠状动脉渗漏。
将离体心脏(豚鼠)用添加了1/3体积5%人白蛋白或6% HES(200/0.5或450/0.7)的Krebs-Henseleit缓冲液恒压灌注。在EG消化(肝素酶)后以及使用硝基-L-精氨酸(NO-L-Ag)时也测定冠状动脉血流。
冠状动脉血流(“白蛋白”组为9.50±1.09、“HES 200”组为5.10±0.49、“HES 450”组为4.87±1.19、“对照组”为4.15±0.09 ml/min/g,每组n = 5 - 6)与灌注液粘度(分别为0.83、1.02、1.24和0.77 cP)无关。NO-L-Ag和肝素酶减弱了白蛋白引起的扩张,但并非累加作用。单独使用NO-L-Ag在输注HES 450期间抑制冠状动脉血流。电子显微镜显示冠状动脉EG为300 nm,肝素酶处理后降至20 nm。培养的内皮细胞最初具有20 nm的EG。
尽管粘度较低,但只要EG含有负性基团,白蛋白比HES诱导更大的内皮剪切应力。HES 450即使通过甚至是基本的EG也会引起一些NO介导的扩张。培养的内皮细胞仅表达基本的糖萼,限制了它们作为模型系统的用途。