Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential

被引:315
作者
Becker, Bernhard F. [1 ]
Chappell, Daniel [2 ]
Bruegger, Dirk [2 ]
Annecke, Thorsten [1 ,2 ]
Jacob, Matthias [2 ]
机构
[1] Univ Munich, Dept Physiol, Walter Brendel Ctr Expt Med, D-80336 Munich, Germany
[2] Univ Munich, Clin Anesthesiol, D-80336 Munich, Germany
关键词
Albumin; Hydrocortisone; Ischaemia; Lipopolysaccharide; Permeability; ATRIAL-NATRIURETIC-PEPTIDE; CELL GLYCOCALYX; HEPARAN-SULFATE; IN-VIVO; 5-PERCENT ALBUMIN; CAROTID-ARTERY; TNF-ALPHA; CAPILLARY; DYSFUNCTION; ISCHEMIA;
D O I
10.1093/cvr/cvq137
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Damage of the endothelial glycocalyx, which ranges from 200 to 2000 nm in thickness, decreases vascular barrier function and leads to protein extravasation and tissue oedema, loss of nutritional blood flow, and an increase in platelet and leucocyte adhesion. Thus, its protection or the restoration of an already damaged glycocalyx seems to be a promising therapeutic target both in an acute critical care setting and in the treatment of chronic vascular disease. Drugs that can specifically increase the synthesis of glycocalyx components, refurbish it, or selectively prevent its enzymatic degradation do not seem to be available. Pharmacological blockers of radical production may be useful to diminish the oxygen radical stress on the glycocalyx. Tenable options are the application of hydrocortisone (inhibiting mast-cell degranulation), use of antithrombin III (lowering susceptibility to enzymatic attack), direct inhibition of the cytokine tumour necrosis factor-alpha, and avoidance of the liberation of natriuretic peptides (as in volume loading and heart surgery). Infusion of human plasma albumin (to maintain mechanical and chemical stability of the endothelial surface layer) seems the easiest treatment to implement.
引用
收藏
页码:300 / 310
页数:11
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