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Background As a first step toward the development of an artificial placenta, we investigated the relationship between blood flow rate through an arteriovenous (A-V) circuit/oxygenator and both CO 2 elimination and hemodynamic stability in a small animal model. Methods Male New Zealand rabbits (N = 10) with an average weight of 2.7 ± 0.2 kg were anesthetized, paralyzed, and heparinized before carotid-jugular cannulation. A tracheostomy tube, an arterial catheter, and an aortic flow probe were placed. Arteriovenous flow through a custom-made, low-resistance, 0.5 m 2 hollow fiber oxygenator was initiated. Oxygen sweep flow was maintained at 300 mL/min, whereas blood flow was controlled at 10 to 40 mL/(kg min). Ventilation was discontinued during each blood flow rate trial. Hemodynamic and preoxygenator and postoxygenator blood gas data were recorded 30 minutes after initiation of each flow rate. CO 2 removal was the product of the oxygen sweep gas flow rate and the sweep flow exhaust CO 2 content as determined by capnometry. Data were analyzed by analysis of variance with post hoc Dunnett's t test. Results CO 2 removal increased and Paco 2 decreased as a function of A-V blood flow rate. Simultaneously, systolic blood pressure did not significantly change. CO 2 removal was effective at device flows greater than 20% of cardiac output. Conclusion In this rabbit model, A-V blood flows at 25% to 30% of cardiac output allow full gas exchange without hemodynamic compromise. This model raises the possibility of using A-V support and an artificial placenta in newborns with respiratory failure.

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.1 Using a 4-hour arteriovenous (AV) rabbit model of ECC,2 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 × 10— 10 mol·cm—2·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. Perfusion (2007) 22, 193—200.

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.

Reliable, real-time, in vivo sensing (intravascular) of blood gases and electrolytes remains a difficult challenge owing to biocompatibility issues that occur when chemical sensors are implanted into the blood stream. Recently, local release of nitric oxide (NO) at the sensor/blood interface has been suggested as a potential solution to this problem. However, the lifetime of NO release from thin polymer films coated on implanted sensors is limited by the reservoir of NO donor loaded within the polymeric coating. To continuously produce NO at the sensor/blood interface, a novel approach to catalytically decompose endogenous S-nitrosothiols (RSNOs) in blood to generate NO in situ is reported herein. Metallic copper particles of two different sizes (3 μm and 80 nm) are embedded as catalysts in thin polymer coatings on the surface intravascular electrochemical oxygen sensing catheters. Oxygen levels (partial pressure of oxygen; PO(2)) provided by the copper particle/polymer coated sensors are, on average, more accurate than values obtained from non-NO generating control sensors when both types of sensors are implanted in porcine arteries for 19-20 h. Upon termination of each in vivo study, catheters were explanted and examined for surface thrombosis via both visual image and lactate dehydrogenase (LDH) assay. The results indicate that the Cu(0)-catalyst coatings significantly reduce the occurrence of surface thrombosis, likely from the ability to generate NO from endogenous RSNO species at the sensor/blood interface.

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.