Hollow fiber artificial lungs are increasingly being used for long-term applications. However, clot formation limits their use to 1-2 weeks. This study investigated the effect of nitric oxide generating (NOgen) hollow fibers on artificial lung thrombogenicity. Silicone hollow fibers were fabricated to incorporate 50 nm copper particles as a catalyst for NO generation from the blood. Fibers with and without (control) these particles were incorporated into artificial lungs with a 0.1 m2 surface area and inserted in circuits coated tip-to-tip with the NOgen material. Circuits (N=5/each) were attached to rabbits in a pumpless, arterio-venous configuration and run for 4 hrs at an activated clotting time of 350-400s. Three control circuits clotted completely, while none of the NOgen circuits failed. Accordingly, blood flows were significantly higher in the NOgen group (95.9 ± 11.7, p < 0.01) compared to the controls (35.2 ± 19.7) (ml/min), and resistance was significantly higher in the control group after 4 hours (15.38 ± 9.65, p<0.001) than in NOgen (0.09 ± 0.03) (mmHg/mL/min). On the other hand, platelet counts and plasma fibrinogen concentration expressed as percent of baseline in control group (63.7 ± 5.7%, 77.2 ± 5.6% [p<0.05]) were greater than those in the NOgen group (60.4 ± 5.1%, 63.2 ± 3.7%). Plasma copper levels in the NOgen group were 2.8 times baseline at 4 hours (132.8 ± 4.5 μg/dl) and unchanged in the controls. This work demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs.

The functions of anti‐fouling, zwitterionic polycarboxybetaine (pCB) coating, and anti‐platelet nitric oxide (NO) release replicate key anticoagulant properties of the endothelium. The two approaches, only tested separately thus far, are paired on gas permeable polydimethylsiloxane (PDMS) membranes and evaluated for fibrinogen (Fg) and platelet adsorption. Uncoated (control) and pCB‐coated PDMS separate sheep plasma (108 platelets per milliliter) and gas flow chambers within bioreactors used in this study, and either 100 or 0 ppm of NO/N2 flows through the gas chamber so PDMS transfers NO into flowing plasma. Surface‐adsorbed platelets are quantified using a lactate dehydrogenase assay after 8h plasma recirculation. Fg and platelet adsorption on pCB‐coated PDMS are 10.40% ± 3.0% of control (p < 0.01) and 23.3% ± 7.4% (p < 0.01) of control, respectively. NO flux alone limits platelet adsorption to 79.0% ± 5.0% (p < 0.05) of control. Together, NO and pCB reduce platelet adsorption to 6.90% ± 1.30% of control (p < 0.001). The data suggest that pCB coating and NO act in concert to reduce platelet fouling at significantly higher levels than either pCB coating or NO release alone.

and platelet activation on the surfaces of these devices lead to clot formation. This, in turn, causes device failure and thromboembolic complications. The most common solution to this problem is systemic anticoagulation, but this leads to bleeding complications that can also contribute to patient morbidity and mortality. [ 1-3 ] Anticoagulation that is limited only upon device surfaces could remedy these shortcomings. Two methods of surface focused anticoagulation have demonstrated some promise in reducing coagulation: surface coatings designed to limit nonspecifi c protein adsorption and anti-platelet surface NO release. Surface coatings only reduce coagulation in the device and thus have no systemic anticoagulant effect. Various commercial anti-thrombogenic coatings have shown better preservation of platelet counts than the uncoated control surface [ 4,5 ] during short-term applications. However, these surface coatings have not yet proven suffi cient to allow the elimination of systemic anticoagulation or long-term use of high surface area artifi cial organs without signifi cant decrease in systemic platelet concentration. [ 6,7 ] Nitric oxide is released from biomaterials into fl owing blood, [ 8-12 ] but has a short half-life of 2-5 seconds [ 8 ] in blood prior to being scavenged. Thus, its systemic effects are minor, and it has been examined as a means to focus anticoagulation at biomaterials' surfaces rather than systemically. Several means of supplying surface NO fl ux have been tested. They include NO release from a stored pool in the biomaterial, NO generation from endogenous sources in blood, and NO delivery via the gas fl ow in artifi cial lungs. [ 9-12 ] Early studies examining the latter approach were largely unsuccessful. These studies did not quantify surface NO fl ux, and it was likely insuffi cient. [ 13 ] More recent studies with proven, endothelial levels of NO fl ux (>2 × 10 −10 mol/min/cm 2) have been successful, reducing platelet adhesion in tubing and catheters by approximately 40%, [ 9,10 ] and markedly reducing coagulation and increasing longevity in artifi cial lungs. [ 12 ] Although positive, these studies were all for a period of 4 hours. Longer-term effectiveness in these settings is unknown. Additionally, use of NO in high surface area artifi cial organs could lead to excessive generation of methemoglobin in the blood, limiting the possible fl ux rates, and anticoagulation. In this study, we hypothesize that the combination of antiadsorptive coatings and surface NO fl ux will lead to more This study examines platelet adhesion on surfaces that combine coatings to limit protein adsorption along with "anti-platelet" nitric oxide (NO) release. Uncoated and poly-2-methoxyethylacrylate (PMEA) coated, gas permeable polypropylene (PP) membranes were placed in a bioreactor to separate plasma and gas fl ows. Nitrogen with 100/500/1000 ppm of NO was supplied to the gas side as a proof of concept. On the plasma side, platelet rich plasma (PRP, 1 × 108 cell/mL) was recirculated at low (60)/high ...

The compliant Thoracic Artificial Lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL’s long term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anti-coagulant coatings was attached to sheep (n=5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was utilized. cTAL resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for non-device related issues. The cTAL’s resistance averaged 1.04±0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180±8 mL/min of oxygen with 3.18±0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis, but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0±0.1 g/dL thereafter. In a fourteen day experiment, the cTAL without anti-coagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged, except for device attachment related hemodilution. This suggests that patients treated with the cTAL shouldn’t require multiple blood transfusions. Once tested with anti-coagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.