title: Perspectives in microvascular fluid handling: does the distribution of coagulation factors in human myocardium comply with plasma extravasation in venular coronary segments?
abstract: BACKGROUND
  Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels.
  
  
  RESULTS
  Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle.
  
  
  CONCLUSIONS
  Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart.
authors.affiliation: Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany. matthias.jacob@med.uni-muenchen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Jacob
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappell
authors.forename: Mechthild
authors.initials: M
authors.lastname: Stoeckelhuber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Welsch
authors.forename: Markus
authors.initials: M
authors.lastname: Rehm
authors.forename: Dirk
authors.initials: D
authors.lastname: Bruegger
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
authors.forename: Peter
authors.initials: P
authors.lastname: Conzen
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Becker
mesh_terms: D000328:Adult; D001160:Arterioles / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability; D002311:Cardiomyopathy, Dilated / Q000097:blood*; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008208:Lymphatic System / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011486:Protein C / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014699:Venules / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C; D012709:Serum Albumin; D018180:Thrombomodulin; D013925:Thromboplastin