Mechanism of antithrombogenicity of a new heparinized hydrophilic polymer: chronic in vivo studies and clinical application.
A new heparinized hydrophilic polymer, H-RSD (graftcopolymer composed of ethylene, vinyl acetate, vinyl chloride, polyethyleneglycolmethacrylate, quartenized dimethylaminoethylmethacrylate and ionically bound heparin), continuously releases heparin from its surface at the rate of approximately 0.004 units/cm2/min when placed in the plasma. It has excellent antithrombogenic and mechanical properties for a biomaterial. In vivo evaluation for thrombogenically using IVC indwelling catheter method in dogs revealed excellent antithrombogenicity over 2 wks. Use of H-RSD as a coating material on other synthetic polymers has also been studied, Catheters made of polyurethane were coated with H-RSD 20 mu, 50 mu, 100 mu, and 150 mu in thickness, and were tested for thrombogenicity in the dog. Catheters coated with 20 mu of H-RSD caused moderate to severe thrombus in the IVC after 2 wks, but catheters coated with H-RSD 50 mu or more were completely free of thrombus formation after 2 wks. Scanning electron micrograph showed neither fibrin clots nor platelet adhesion on the surface of H-RSD catheters. Heparin concentration in H-RSD catheters was analyzed by electron probe X-ray microanalyzer before and after in vivo tests. Heparin concentration became higher as the thickness of H-RSD coating increased. After a 2 wk test, heparin concentration in the catheters decreased to about 85% of the initial value. Good retention of heparin in the H-RSD catheters after in vivo tests was found to correlate with continuous release of heparin from its surface. H-RSD catheters can be sterilized with ethylene oxide gas. Pyrogen and acute toxicity tests on extracts of H-RSD were negative. H-RSD catheters were used in 9 patients for up to 3 wks. Thrombus formation observed by pullout venography or at autopsy in these patients was less than those seen in patients with silicone rubber or polyethylene catheters.
D000085:Acetates; D000818:Animals; D002404:Catheterization; D004285:Dogs; D005026:Ethylene Glycols; D005030:Ethylenes; D005069:Evaluation Studies as Topic; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008689:Methacrylates; D011095:Polyethylenes; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology*; D012826:Silicone Elastomers; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control*; D014752:Vinyl Chloride; D014753:Vinyl Compounds
D000085:Acetates; D005026:Ethylene Glycols; D005030:Ethylenes; D008689:Methacrylates; D011095:Polyethylenes; D011108:Polymers; D012826:Silicone Elastomers; D014753:Vinyl Compounds; D006493:Heparin; D014752:Vinyl Chloride