Chappell Daniel, Jacob Matthias, Hofmann-Kiefer Klaus, Bruegger Dirk, Rehm Markus, Conzen Peter, Welsch Ulrich, Becker Bernhard F
Clinic of Anesthesiology, Ludwig-Maximilians University Munich, Munich, Germany.
Anesthesiology. 2007 Nov;107(5):776-84. doi: 10.1097/01.anes.0000286984.39328.96.
Hydrocortisone protects against ischemia-reperfusion injury, reduces paracellular permeability for macromolecules, and is routinely applied in the prevention of interstitial edema. Healthy vascular endothelium is coated by the endothelial glycocalyx, diminution of which increases capillary permeability, suggesting that the glycocalyx is a target for hydrocortisone action.
Isolated guinea pig hearts were perfused with Krebs-Henseleit buffer. Hydrocortisone was applied in a stress dose (10 microg/ml) before inducing 20 min of ischemia (37 degrees C). Hearts were reperfused for 20 min at constant flow (baseline perfusion pressure, 70 cm H2O) with Krebs-Henseleit buffer or Krebs-Henseleit buffer plus 2 g% hydroxyethyl starch (130 kd). Coronary net fluid filtration was assessed directly by measuring transudate formation on the epicardial surface. Hearts were perfusion fixed to visualize the glycocalyx.
Ischemia-induced degradation of the glycocalyx enhanced coronary perfusion pressure (118.8 +/- 17.3 cm H2O) and increased vascular permeability (8 +/- 0.2 microl x min(-1) x cm H2O(-1) at baseline vs. 34 +/- 3.3 microl x min(-1) x cm H2O(-1) after reperfusion). Enzymatic digestion of the glycocalyx (heparinase) elicited similar effects. Hydrocortisone reduced postischemic oxidative stress, perfusion pressure (86.3 +/- 6.4 cm H2O), and transudate formation (11 +/- 0.6 microl x min(-1) x cm H2O(-1)). Applying colloid augmented this (70.6 +/- 5.6 cm H2O and 9 +/- 0.5 microl x min(-1) x cm H2O(-1)). Postischemic shedding of syndecan-1, heparan sulfate, and hyaluronan was inhibited by hydrocortisone, as was release of histamine from resident mast cells. Electron microscopy revealed a mostly intact glycocalyx after hydrocortisone treatment, but not after heparinase treatment.
Hydrocortisone preserves the endothelial glycocalyx, sustaining the vascular barrier and reducing interstitial edema. The effect of colloids suggests that prevention of postischemic rise in coronary resistance by hydrocortisone could also be based on alleviation of endothelial swelling. Stabilization of myocardial mast cells by hydrocortisone may account for the mitigated inflammatory affect of ischemia-reperfusion.
氢化可的松可预防缺血-再灌注损伤，降低大分子的细胞旁通透性，并常规用于预防间质水肿。健康的血管内皮被内皮糖萼覆盖，其减少会增加毛细血管通透性，这表明糖萼是氢化可的松作用的靶点。
用克雷布斯-亨塞尔特缓冲液灌注离体豚鼠心脏。在诱导20分钟缺血（37℃）前给予应激剂量（10微克/毫升）的氢化可的松。心脏在恒定流量（基线灌注压力70厘米水柱）下用克雷布斯-亨塞尔特缓冲液或克雷布斯-亨塞尔特缓冲液加2%羟乙基淀粉（130kd）再灌注20分钟。通过测量心外膜表面的渗出液形成直接评估冠状动脉净液体滤过。心脏经灌注固定以观察糖萼。
缺血诱导的糖萼降解增加了冠状动脉灌注压力（118.8±17.3厘米水柱）并增加了血管通透性（基线时为8±0.2微升×分钟-1×厘米水柱-1，再灌注后为34±3.3微升×分钟-1×厘米水柱-1）。糖萼的酶促消化（肝素酶）产生了类似的效果。氢化可的松降低了缺血后氧化应激、灌注压力（86.3±6.4厘米水柱）和渗出液形成（11±0.6微升×分钟-1×厘米水柱-1）。应用胶体增强了这种作用（70.6±5.6厘米水柱和9±0.5微升×分钟-1×厘米水柱-1）。氢化可的松抑制了缺血后syndecan-1、硫酸乙酰肝素和透明质酸的脱落，以及驻留肥大细胞组胺的释放。电子显微镜显示氢化可的松处理后糖萼大多完整，但肝素酶处理后则不然。
氢化可的松可保留内皮糖萼，维持血管屏障并减少间质水肿。胶体的作用表明，氢化可的松预防缺血后冠状动脉阻力升高也可能基于减轻内皮肿胀。氢化可的松对心肌肥大细胞的稳定作用可能是缺血-再灌注炎症影响减轻的原因。
