Improvement of bypass circuit biocompatibility: comparison and combination of heparin-coated circuit and nitric oxide gas infusion.
OBJECTIVE
Nitric oxide (NO) gas infusion to the oxygenator, as well as heparin-coated bypass circuits, have been reported to attenuate blood activation induced by the interaction with the artificial surfaces of an extracorporeal bypass circuit. Using a mock circulation model, we compared the effect of each and also evaluated the effect of their combination on attenuating bypass-induced blood activation.


METHODS
A miniature closed bypass circuit was primed with diluted fresh human blood and perfused for 180 minutes using a centrifugal pump. NO gas (0, 50, or 100 ppm) was infused to the oxygenator sweep gas of either a non-heparin-coated or a heparin-coated circuit. Platelet counts, beta-thromboglobulin, platelet factor 4, complement-3 activation products and granulocyte elastase were measured at 0, 30, 60, 120, and 180 minutes after starting the perfusion.


RESULTS
One hundred ppm of NO was statistically equivalent to the heparin-coated circuit for attenuating bypass-induced blood activation, and a combination of the two significantly surpassed the results of either modification alone. Fifty ppm of NO alone provided only a slight attenuation of blood activation as compared with the non-heparin-coated circuit, though the difference was not significant. A combination of 50 ppm NO and the heparin-coated circuit did not significantly enhance the effects of the heparin-coated circuit alone.


CONCLUSIONS
The combination of NO gas infusion and heparin-coated circuits appears to be a useful and promising modification for enhancing the attenuation of bypass-induced blood activation, though the optimal dose of NO infusion in terms of effectiveness and adverse effects to the whole body remains to be established.
Hayashi
Yoshitaka
Y
Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita, Japan.
Sawa
Yoshiki
Y
Hirata
Nobuaki
N
Nishimura
Motonobu
M
Ueda
Hideki
H
Naka
Yoshihisa
Y
Yamaguchi
Takahiro
T
Ohtake
Shigeaki
S
Matsuda
Hikaru
H
D000925:Anticoagulants / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000627:therapeutic use*; D015926:Complement C3a / Q000187:drug effects; D004359:Drug Therapy, Combination; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000592:standards*; D005341:Fibrinolysin / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006353:Heart-Assist Devices; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood / Q000187:drug effects; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000627:therapeutic use; D009573:Nitrites / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D000979:alpha-2-Antiplasmin / Q000187:drug effects; D001620:beta-Thromboglobulin / Q000187:drug effects
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D005343:Fibrinolytic Agents; D018836:Inflammation Mediators; D009566:Nitrates; D009573:Nitrites; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; D001620:beta-Thromboglobulin; C037742:plasmin-plasmin inhibitor complex; D009569:Nitric Oxide; D010978:Platelet Factor 4; D015926:Complement C3a; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase; D005341:Fibrinolysin