title: 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 m(2) 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 h at an activated clotting time of 350-400 s. 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 h (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 h (132.8 ± 4.5 μg/dL) and unchanged in the controls. This study demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs.
authors.affiliation: Departments of Surgery, University of Michigan Medical Center, 1150 W Medical Center Drive B560B MSRBII, Ann Arbor, MI 48109-0686; Department of Internal Medicine, Cardiology, University of Michigan Medical Center; Department of Chemistry, University of Michigan, Ann Arbor, MI.
authors.forename: Kagya A
authors.initials: KA
authors.lastname: Amoako
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Montoya
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.forename: Ahmed B
authors.initials: AB
authors.lastname: Suhaib
authors.forename: Hitesh
authors.initials: H
authors.lastname: Handa
authors.forename: David O
authors.initials: DO
authors.lastname: Brant
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Keith E
authors.initials: KE
authors.lastname: Cook
mesh_terms: D000818:Animals; D001187:Artificial Organs; D001772:Blood Cell Count; D001792:Blood Platelets / Q000378:metabolism; D003300:Copper / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism; D006439:Hemodynamics; D008168:Lung / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D012039:Regional Blood Flow; D026403:S-Nitrosothiols / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D026403:S-Nitrosothiols; D009569:Nitric Oxide; D003300:Copper; D005340:Fibrinogen
keywords: artificial lung; biocompatibility; extracorporeal circulation; nitric oxide; silicone; thrombosis