Clinic of Anesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany.
Shock. 2010 Aug;34(2):133-9. doi: 10.1097/SHK.0b013e3181cdc363.
Adhesion of polymorphonuclear neutrophils (PMN) to coronary endothelium is a key event for cardiac ischemia/reperfusion injury. Adhesion molecules are normally harbored within the glycocalyx, clothing every healthy vascular endothelium, but shed by ischemia/reperfusion. Our aim was to show whether protection of the glycocalyx with either hydrocortisone or antithrombin can reduce postischemic leukocyte adhesion. Isolated guinea pig hearts, perfused with Krebs-Henseleit buffer, were subjected to 20 min of warm (37 degrees C) no-flow ischemia and consecutive 10 min of reperfusion, either in the absence or presence of hydrocortisone (10 microg/mL) or antithrombin (1 U/mL). An intracoronary bolus of 3 x 10 PMN was applied at the end of reperfusion but without prior contact to the drugs. The sequestration of PMN was calculated from the difference between coronary input and output of cells. Expression of the integrin CD11b on PMN was measured before and after coronary passage. Ischemia/reperfusion induced severe degradation of the glycocalyx (coronary venous syndecan-1 release, 171 +/- 15 ng/g heart vs. basal, 19 +/- 2 ng/g; heparan sulfate, 5.27 +/- 0.28 microg/g vs. basal, 0.26 +/- 0.06 microg/g) and increased PMN adhesion (38.1% +/- 3.5% vs. basal, 11.7% +/- 3.1%). Hydrocortisone and antithrombin both not only reduced glycocalyx shedding (syndecan-1 release, 34 +/- 6 ng/g and 26 +/- 5 ng/g; heparan sulfate, 1.96 +/- 0.24 microg/g and 1.28 +/- 0.2 microg/g, respectively), but also PMN adhesion (17.3% +/- 2.2% and 25.4% +/- 3.3%, respectively) after ischemia/reperfusion. Electron microscopy revealed a mostly intact coronary glycocalyx after pretreatment with either drug. Activation of PMN upon coronary passage was not influenced. Preservation of the glycocalyx mitigates postischemic PMN adhesion. Preconditioning with either hydrocortisone or antithrombin should, thus, alleviate vascular leakage, tissue edema, and inflammation.
多形核白细胞（PMN）黏附于冠状动脉内皮是导致心肌缺血/再灌注损伤的关键事件。黏附分子通常存在于糖萼中，覆盖每个健康的血管内皮，但在缺血/再灌注时会脱落。我们的目的是证明用氢化可的松或抗凝血酶保护糖萼是否可以减少缺血后白细胞的黏附。用 Krebs-Henseleit 缓冲液灌注分离的豚鼠心脏，先经历 20 分钟的热缺血（37°C）无血流，然后连续再灌注 10 分钟，无或有氢化可的松（10 μg/mL）或抗凝血酶（1 U/mL）。在再灌注结束时，通过冠状动脉内推注 3×10 的 PMN，但在与药物接触之前。PMN 的隔离是从冠状动脉输入和输出的细胞差异中计算出来的。在冠状动脉通过之前和之后测量 PMN 上整合素 CD11b 的表达。缺血/再灌注引起糖萼严重降解（冠状静脉硫酸乙酰肝素释放，171±15ng/g 心脏与基础相比，19±2ng/g；硫酸乙酰肝素，5.27±0.28μg/g 与基础相比，0.26±0.06μg/g）和 PMN 黏附增加（38.1%±3.5%与基础相比，11.7%±3.1%）。氢化可的松和抗凝血酶不仅减少糖萼脱落（硫酸乙酰肝素释放，34±6ng/g 和 26±5ng/g；硫酸乙酰肝素，1.96±0.24μg/g 和 1.28±0.2μg/g），而且在缺血/再灌注后还减少 PMN 黏附（17.3%±2.2%和 25.4%±3.3%）。电镜显示，在用这两种药物预处理后，冠状动脉的糖萼大多完整。PMN 在冠状动脉通过时的激活不受影响。糖萼的保存减轻了缺血后的 PMN 黏附。因此，用氢化可的松或抗凝血酶预处理应减轻血管通透性、组织水肿和炎症。
