Mechanism of antithrombogenicity of a new heparinized hydrophilic polymer: chronic in vivo studies and clinical application

Abstract

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.