Influence of heparin; of different heparin fractions and of a low molecular weight heparin-like substance on the mechanism of fibrinolysis.
The influence of different heparin fractions and of a synthetic polysulfated polysaccharide (SP54) on the fibrinolytic mechanism was examined. In vitro, a significant shortening of the euglobulin lysis time (ELT) was found after addition of standard mucosa heparin, of high MW heparin and of SP 54 respectively. Low MW heparin fractions had no influence on the ELT. Simultaneously with the shortening of the ELT an activation of factor XII and of kallikrein was observed. A similar effect was found in groups of volunteers after i.v. or s.c. injections and even after oral administration of SP 54. The effect of venous occlusion on the ELT and on the activation of factor XII was considerably increased when heparin or SP 54 was injected 2 h prior to the test. When a comparable concentration of the test substances was added to plasma samples before and after venous occlusion, the effect on the ELT was much less pronounced than after injection whilst the effect on factor XII was comparable in both tests. From these results the conclusion was drawn that activation of fibrinolysis by polysulfated polysaccharides is achieved by an endogenous pathway as well as by an increased availability of the vascular activator. The magnitude of the activation of fibrinolysis partly depends on the MW of the substance but apparently also on the degree of sulfation since a low MW substance with a high number of sulfate bonds such as SP 54 was considerably more active than the low MW fraction of standard heparin.
D000328:Adult; D000818:Animals; D005591:Chemical Fractionation; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D005174:Factor XII / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000032:analysis; D008297:Male; D008970:Molecular Weight; D010958:Plasminogen / Q000032:analysis; D000071228:Polyelectrolytes; D011108:Polymers / Q000008:administration & dosage / Q000494:pharmacology; D012712:Serum Globulins; D013552:Swine; D014680:Veins
D005174:Factor XII; D006493:Heparin; D007610:Kallikreins; D010958:Plasminogen; D000071228:Polyelectrolytes; D011108:Polymers; D012712:Serum Globulins