The gold standard for anticoagulation during extracorporeal circulation (ECC) remains systemic heparinization and the concomitant risk of bleeding in an already critically ill patient could lead to death. Normal endothelium is a unique surface that prevents thrombosis by the release of antiplatelet and antithrombin agents. Nitric oxide (NO) is one of the most potent, reversible antiplatelet agents released from the endothelium. Nitric oxide released from within a polymer matrix has been proven effective for preventing platelet activation and adhesion onto extracorporeal circuits. However, the critical NO release (NO flux) threshold for thrombus prevention during ECC has not yet been determined. Using a 4-hour arteriovenous (AV) rabbit model of ECC, we sought to find this threshold value for ECC circuits, using an improved NO-releasing coating (Norel-b). Four groups of animals were tested at variable NO flux levels. Hourly blood samples were obtained for measurement of arterial blood gases, platelet counts, fibrinogen levels and platelet function (via aggregometry). A custom-built AV circuit was constructed with 36 cm of poly(vinyl)chloride (PVC) tubing, a 14 gauge (GA) angiocatheter for arterial access and a modified 10 French (Fr) thoracic catheter for venous access. The Norel-b coating reduced platelet activation and thrombus formation, and preserved platelet function - in all circuits that exhibited an NO flux of 13.65 x 10(10) mol x cm(-2) x min(-1). These results were significant when compared with the controls. With the Norel-b coating, the NO flux from the extracorporeal circuit surface can be precisely controlled by the composition of the polymer coating used, and such coatings are shown to prevent platelet consumption and thrombus formation while preserving platelet function in the animal.

To identify nonthrombogenic devices to be used in extracorporeal circulation (ECC), an efficient, small animal model is required. Initially, a venovenous (VV) model in rabbits was designed for this purpose and was a good representation of ECC. Technical difficulties in the VV model led to the development of a more simplistic arteriovenous (AV) model. Anesthetized, tracheotomized, 3-kg rabbits were used for both models. Circuits were constructed of PVC tubing. The VV model used 8-Fr umbilical artery catheters for both drainage and reinfusion, and the AV model used a 14-GA angiocatheter for carotid artery access and a 10-Fr thoracic catheter for venous access. The AV model included a chamber to mimic oxygenator or filter modeling. Hourly measurements included blood gases, platelet counts, and fibrinogen levels for the 4-hour studies. The VV ECC groups demonstrated platelet consumption like that seen in the clinical arena. The AV model demonstrated the same with or without additional surface area within the chamber. The AV model was deemed to be superior due to its simplicity, ability for filter modeling, and decrease in intensive monitoring. However, both models are excellent designs for nonthrombogenic surface testing.

The development of a nonthrombogenic artificial surface for use with indwelling sensors or catheters remains an elusive goal despite decades of ongoing research. In vivo studies are both labor intensive and costly, and are therefore an inefficient way to rapidly screen possible surface materials. The following in vitro model used glass, polyvinyl chloride (PVC), and polypropylene test tubes incubated with 111In-labeled rabbit platelets and illustrated that, despite equivalent platelet count and function, platelet adhesion was greatest on glass (n = 13), with PVC (n = 17) at 67 +/- 8% and polypropylene (n = 13) at 43 +/- 5% when compared with glass. Extrapolating this method by coating test tubes with new, nonthrombogenic materials is a quick and reliable way to screen material before embarking upon more lengthy in vivo animal studies.

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