Chronic performance of polyurethane catheters covalently coated with ATH complex: A rabbit jugular vein model
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Covalent complexes of antithrombin (AT) and heparin (ATH) have superb anticoagulant activity towards thrombin and factor Xa. Stability of polyurethane central venous catheters covalently modified with radiolabeled ATH was studied using a roller pump with saline or protease P-5147. Saline wash removed loosely bound ATH molecules to decrease graft density from 26 to 12 pmol/cm2. However, only slightly more ATH was removed by strong protease (from 12 to 7 pmol/cm2). To evaluate ATH-coated, heparin-coated, and uncoated catheters, a chronic rabbit jugular vein model was developed with catheters maintained for up to 30-106 days. Lumen occlusion was tested by drawing blood twice daily. Although unmodified or heparin-coated catheters occluded within 5-7 days after insertion, all ATH catheters remained patent throughout the experiment. Scanning electron microscopy (SEM) analysis of heparin and uncoated catheters revealed extensive thrombosis (lumen+mural) while ATH catheters were unaffected. Visual observation showed significant deposition of protein and cells on control and heparin-modified catheters and, to a lesser degree, on ATH-coated surfaces. SEM showed no fibrin inside or outside of ATH catheters, which remained patent in extended studies out to 106 days. Although atomic force microscopy showed ATH coatings to be rough, 6-fold higher anti-factor Xa activity likely contributed to increased patency. Our data confirm that ATH-modified catheters are stable and have superior potency compared to heparin or control catheters.
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