Nitric Oxide Increases Leukocyte Granule Release During Simulated Extracorporeal Circulation[1]

Background: Nitric Oxide (NO) is reported to posses anti-inflammatory properties. The aim of this study was to investigate if nitric oxide affects leukocyte response during simulated extracorporeal circulation (SECC). Methods: Human blood was circulated for 23 hours through SECC circuit. Control group C (n = 5) was ventilated with an oxygen/air mixture, and NO was added in the study group (n = 5). Leukocyte response was determined by release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) and by oxygen free radical production, estimated using chemiluminescence. Results: Addition of NO significantly increased MPO at 30 minutes and 120 minutes of SECC and HNL at 120 minutes of SECC. Oxygen free radical production in whole blood was generally not affected by NO. Similarly, no significant differences were observed between the groups with regard to the chemiluminescence in isolated granulocytes. Conclusions: Nitric oxide increased release of leukocyte granule derived proteins; MPO and HNL at an early stage of simulated extracorporeal circulation. At the same time, nitric oxide did not affect the whole blood and leukocyte capacity to produce oxygen free radicals.

Key words:

Nitric oxide - - Extracorporeal circulation - - Inflammatory reaction - - Leukocytes - - Oxygen free radicals

1 Presented at the 47^th Annual Meeting for Scandinavian Association for Thoracic Surgery, Aug 29^th, 1999, Aalborg, Denmark

References

• 1 Teoh K HT, Bradley C A, Gauldie J, Burrows H. Steroid inhibition of cytokine-mediated vasodilation after warm heart surgery.  Circulation.. 1995;  92 (suppl II) 347-53
• 2 Kirklin J K. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass.  Ann Thor Surg.. 1991;  51 529-31
• 3 Dowing S W, Edmunds L H Jr. Release of vasoactive substances during cardiopulmonary bypass.  Ann Thorac Surg.. 1992;  54 1236-43
• 4 Welch G, Loscalzo J. Nitric Oxide and its role in the cardiovascular system.  Prog Cardiovasc Dis.. 1995 Sept-Oct;  38 87-104
• 5 Welch G, Loscalzo J. Nitric oxide and the cardiovascular system.  J Cardiac Surg.. 1994;  74 1121-5
• 6 Fukuda H, Sawa Y, Kadoba K, Taniguchi K, Shimazaki Y, Matsuda H. Supplement of nitric oxide attenuates neutrophil-mediated reperfusion injury.  Circulation.. 1995;  (Suppl II) 413-6
• 7 Niu Xiao-fei, Smith C W, Kubes P. Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils.  Circ Res.. 1994;  74 1133-40
• 8 Ungureanu-Longrois D, Balligand J-L, Kelly R A, Smith T W. Myocardial contractile dysfunction in the systemic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes.  J Mol Cell Cardiol.. 1995;  127 155-67
• 9 Granger N D, Kubes P. Nitric oxide as anti-inflammatory agent.  Methods Enzymol.. 1996;  269 434-42
• 10 Xu S Y, Peterson C GB, Carlson M, Venge P. The development of an assay for human neutrophil lipocalin (HNL)- to be used as a specific marker of neutrophil activity in vivo and in vitro.  J Immunol Met.. 1994;  171 245-52
• 11 Borowiec J, Venge P, Henze A, Nilsson B, Stiernström H. Biomaterial dependent blood activation during simulated extracorporeal circulation. A study in heparin-coated and uncoated circuits.  Thorac Cardiovasc Surgeon.. 1997;  45 295-301
• 12 Goligorsky M D, Noiri E, Peresleni T, Hu Y. Role of nitric oxide in cell adhesion and locomotion.  Exp Nephrol.. 1996 Nov-Dec;  4 314-21
• 13 Balligard J-L, Ungureanu D, Kelly R A. et al . Abnormal contractile function due to induction of nitric oxide sythesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.  J Clin Invest.. 1993;  91 2314-9
• 14 Morita K, Matheis G, Buckberg G D. et al . Studies of hypoxemic/reoxygenation injury: Without aortic clamping. V. Role of the L-arginine-nitric oxide pathway: the nitric oxide paradox.  J Thorac Cardiovasc Surg.. 1995;  110 1200-11
• 15 Kooy N, Royall J, Ye Y, Beckman J. Evidence for in vivo peroxynitrite production in human lung injury.  Am J Respir Crit Care Med.. 1995;  151 1250-4
• 16 Hayashi Y, Sawa Y, Nishimura M. et al . Nitrit oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.  ASAIO Journal.. 1998;  44 M456-61
• 17 Mellgren K, Friberg L G, Hedner T, Wennmalm Å, Wadenvik H. Nitrit oxide in the sweep gas reduces platelet activation during experimental perfusion.  Ann Thorac Surg.. 1996;  61 1856-64
• 18 Konishi R, Shimizu R, Firestone L. et al . Nitrit oxide prevents human platelet adhesion to fiber membranes in whole blood.  ASAIO J.. 1996;  42 M850-3
• 19 Sly M K, Prager M D, Jun Li. et al . Platelet and neutrophil distributions in pump oxygenator circuits III. Influence of nitric oxide gas infusion.  ASAIO J.. 1996;  42 M494-9

1 Presented at the 47^th Annual Meeting for Scandinavian Association for Thoracic Surgery, Aug 29^th, 1999, Aalborg, Denmark