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

J Biomed Mater Res A. 2013 Dec;101(12):3511-9. doi: 10.1002/jbm.a.34655. Epub 2013 Apr 24.

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.

Keywords: artificial lung; biocompatibility; extracorporeal circulation; nitric oxide; silicone; thrombosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Artificial Organs*
  • Blood Cell Count
  • Blood Platelets / metabolism
  • Copper / blood
  • Fibrinogen / metabolism
  • Hemodynamics
  • Lung / blood supply
  • Lung / pathology*
  • Lung / ultrastructure
  • Nitric Oxide / metabolism*
  • Rabbits
  • Regional Blood Flow
  • S-Nitrosothiols / metabolism
  • Thrombosis / metabolism*
  • Time Factors
  • Tissue Engineering / methods*

Substances

  • S-Nitrosothiols
  • Nitric Oxide
  • Copper
  • Fibrinogen