Fabrication and in vivo thrombogenicity testing of nitric oxide generating artificial lungs

Abstract

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.

Multimodal, Biomaterial‐Focused Anticoagulation via Superlow Fouling Zwitterionic Functional Groups Coupled with Anti‐Platelet Nitric Oxide Release

“…Blood‐contacting medical devices typically fail in the long‐term due to clot formation. Significant advances have been made toward achieving materials capable of longer‐term use, including (1) heparin coatings to reduce thrombin generation, (2) various coatings that resist adsorption of plasma proteins, and (3) nitric oxide (NO) gas to reduce platelet activation . Each technology is inspired by a single mechanism of the rather multimodal approach used by the endothelium to control coagulation.…”

“…On their own, pCB grafted surfaces have shown undetectable nonspecific protein adsorption (<0.3 ng cm −2 ) from single‐protein solutions or complex media by surface plasmon resonance. NO releasing or generating surfaces are capable of reducing platelet adsorption by ≈40%, and markedly reduce clot formation in artificial lungs . Unfortunately, in applications requiring large surface‐area‐to‐volume ratios (e.g., artificial lungs and kidneys) or small bore architecture (vascular grafts), NO secretion or zwitterionic grafting alone may not be adequate to counter coagulation and preserve device function, particularly when device use of weeks to months is required.…”

Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung

“…The WBC and Plt were corrected for hemodilution using standard methods. 21 Mean arterial pressure (MAP) was recorded hourly from pressure transducers coupled with a patient monitor (Solar 8000, Marquette Electronics, Milwaukee, WI). CTAL blood inlet and outlet pressures were measured with pressure transducers (ICU Medical, San Clemente, CA) coupled with a data acquisition system (Biopac Systems, Goleta, CA), and cTAL flowrate was measured via an ultrasonic flow meter and probe (TS410 with 14PXL, Transonic, Ithaca, NY).…”

Current and future status of extracorporeal life support for respiratory failure in adults

“…The next generation of devices will have surfaces which inhibit platelet adhesion to the surface, usually by causing platelet 'anesthesia' for those platelets which get very close to the surface. Currently, this is being done with nitric oxide eluting from the plastic [17,18]. The use of nitric oxide or similar materials to prevent platelet adhesion will greatly decrease the need for anticoagulation, and when combined with surface antifibrin chemicals, may eliminate the need for anticoagulation altogether.…”