Perspectives in Microvascular Fluid Handling: Does the Distribution of Coagulation Factors in Human Myocardium Comply with Plasma Extravasation in Venular Coronary Segments?

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. Methods
and 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. Copyright (C) 2010 S. Karger AG, Basel