Heparin adheres to the damaged arterial wall and inhibits its thrombogenicity.
Heparin binds to thrombogenic extracellular matrices as well as to smooth muscle cells of the vascular wall in vitro. The inhibitory effects of heparin on thrombogenicity of the damaged arterial wall were examined in vivo using small mesenteric arteries of rats and a video recording system attached to a microscope. To induce thrombosis, we damaged the vessel wall over a short segment by compression and exposed the media to the blood stream. A platelet-rich thrombus enlarged gradually at the damaged site, occluded the vascular lumen for a short period, and then flowed away. Compression damage induced such thrombus formation several times. Heparin (500 units/ml) was given in three different ways: intravenous and intra-arterial administration (both 300 units/kg) and intraluminal application under stopped-flow conditions (less than 0.01 ml) for 1-2 minutes with subsequent draining out. Intravenous heparin significantly decreased both the total duration and the number of thrombotic occlusions, whereas intra-arterial heparin abolished thrombotic occlusion. Both routes of heparin administration similarly prolonged the blood coagulation time. Intraluminal application of heparin significantly inhibited subsequent thrombus formation after restoring the flow without changes in the blood coagulation time. After an intra-arterial administration or intraluminal application of fluorescein isothiocyanate-bound heparin, strong fluorescence was observed only at the damaged vascular segment. A heparin fraction with low affinity to antithrombin III or chondroitin sulfate A did not inhibit thrombosis. To clarify anticoagulant activity of vascular wall-bound heparin, damaged carotid arterial segments of rats were incubated (inside out) in platelet-poor plasma with thrombin, and fibrin clot formation around the segments with or without heparin binding was measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Araki
H
H
Department of Pharmacology, Kumamoto University Medical School, Japan.
Muramoto
J
J
Nishi
K
K
Jougasaki
M
M
Inoue
M
M
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016650:Fluorescein-5-isothiocyanate; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000517:prevention & control*
D006493:Heparin; D016650:Fluorescein-5-isothiocyanate