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The effect of aprotinin on hypoxia–reoxygenation-induced changes in neutrophil and endothelial function

Published online by Cambridge University Press:  28 January 2005

D. Harmon ,
W. Lan  and
G. Shorten
D. Harmon
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
W. Lan
Affiliation:
Cork University Hospital and University College Cork, Department of Surgery, Cork, Ireland
G. Shorten
Affiliation:
Cork University Hospital and University College Cork, Department of Anaesthesia and Intensive Care Medicine, Cork, Ireland
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Summary

Background and objective: An acute inflammatory response associated with cerebral ischaemia–reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery.

Methods: Human neutrophil CD11b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1β supernatant concentrations in response to in vitro hypoxia–reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL−1). Adhesion molecule expression was quantified using flow cytometry and IL-1β concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student–Newman–Keuls test as appropriate.

Results: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170 ± 46% vs. 91 ± 27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170 ± 46 % vs. 129 ± 40%) (P = 0.04)] (n = 8). Hypoxia–reoxygenation increased endothelial cell ICAM-1 expression (155 ± 3.7 vs. 43 ± 21 mean channel fluorescence, P = 0.0003) and IL-1β supernatant concentrations compared to normoxia (3.4 ± 0.4 vs. 2.6 ± 0.2, P = 0.02) (n = 3). Hypoxia–reoxygenation produced greater upregulation of ICAM-1 expression [(155 ± 3.3 vs. 116 ± 0.7) (P = 0.001)] and IL-1β supernatant concentrations [(3.4 ± 0.3 vs. 2.6 ± 0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3).

Conclusions: Hypoxia–reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1β concentrations is decreased by aprotinin at clinically relevant concentrations.

Keywords

HYPOXIA–ISCHAEMIA, BRAINAPROTININENDOTHILIUMNEUTROPHIL
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 12 , December 2004 , pp. 973 - 979
Copyright
© 2004 European Society of Anaesthesiology

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References

Alderman EL, Levy JH, Rich JB, et al. Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial. J Thorac Cardiovasc Surg 1998; 116: 716–730.Google Scholar
Murkin JM. Attenuation of neurologic injury during cardiac surgery. Ann Thorac Surg 2001; 72: S1838–S1844.Google Scholar
Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21: 232–244.Google Scholar
del Zoppo GJ, Schmid-Schonbein GW, Mori E, Copeland Br, Chang CM. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 1991; 22: 1276–1283.Google Scholar
Mori E, del Zoppo GJ, Chambers D, et al. Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons. Stroke 1992; 23: 712–718.Google Scholar
Jansen P, Baufreton C, Besnerais P, et al. Heparin coated circuits and aprotinin prime for coronary artery bypass grafting. Ann Thorac Surg 1996; 61: 1363–1366.Google Scholar
Lord RA, Roath OS, Thompson JF, Chant AD, Francis JL. Effect of aprotinin on neutrophil function after major vascular surgery. Br J Surg 1992; 79: 517–521.Google Scholar
Wachtfogel YT, Kucich U, Hack CE, et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 1993; 106: 1–10.Google Scholar
Asimakopoulos G, Lidington EA, Mason J, O'Haskard D, Taylor KM, Landis RC. Effect of aprotinin on endothelial activation. J Thorac Cardiovasc Surg 2001; 122: 123–128.Google Scholar
Aoki M, Jonas RA, Nomura F, et al. Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest. Ann Thorac Surg 1994; 58: 146–153.Google Scholar
Kamiya T, Katayama Y, Kashiwagi F, Terashi A. The role of bradykinin in mediating ischaemic brain edema in rats. Stroke 1993; 24: 571–576.Google Scholar
Gurevitch J, Barak J, Hochhauser E, Paz Y, Yakirevich V. Aprotinin improves myocardial recovery after ischemia and reperfusion. Effects of the drug on isolated rat hearts. J Thorac Cardiovac Surg 1994; 108: 109–118.Google Scholar
Carlos TM, Harlan JM. Leukocyte-endothelial cell adhesion molecules. Blood 1994; 84: 2068–2101.Google Scholar
Scannell G, Waxman K, Vazira ND, et al. Hypoxia-induced alterations of neutrophil membrane receptors. J Surg Res 1995; 59: 141–145.Google Scholar
Mataki H, Inagaki T, Yokoyama M, Maeda S. ICAM-1 expression and cellular injury in cultured endothelial cells under hypoxia/reoxygenation. Kobe J Med Sci 1994; 40: 49–63.Google Scholar
Clark ET, Desai TR, Hynes KL, Gewertz BL. Endothelial cell response to hypoxia–reoxygenation is mediated by IL-1. J Surg Res 1995; 58: 675–681.Google Scholar
Shreeniwas R, Koga S, Karakurum M, et al. Hypoxia-mediated induction of endothelial cell interleukin-1A. An autocrine mechanism promoting expression of leukocyte adhesion molecules on vessel surface. J Clin Invest 1992; 90: 2333–2339.Google Scholar
Asimakopoulos G, Thompson R, Nourshargh S, et al. An anti-inflammatory property of aprotinin detected at the level of leukocyte extravasation. J Thorac Cardiovasc Surg 2000; 120: 361–369.Google Scholar
Sethi S, Singh MP, Dikshit M. Nitric oxide mediated augmentation of polmorphonuclear free radical generation following hypoxia–reoxygenation. Blood 1999: 93; 333–340.Google Scholar
Wellicome SM, Thornhill MH, Pitzalis C, et al. A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1, or lipopolysaccharide. J Immunol 1990; 144: 2558–2565.Google Scholar
Wang X, Feuerstein GZ. Induced expression of adhesion molecules following focal brain ischemia. J Neurotrauma 1995; 12: 825–832.Google Scholar
Zhang W, Smith C, Howlett C, Stanimirovic D. Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in vitro is mediated by IL-1β. J Cereb Blood Flow Metab 2000; 20: 967–978.Google Scholar
Lahat N, Zlotnick AY, Shtiller R, Bar I, Merin G. Serum levels of IL-1, IL-6 and tumor necrosis factor in patients undergoing coronary artery bypass grafts or cholecystectomy. Clin Exp Immunol 1992; 89: 255–260.Google Scholar
Butler J, Parker D, Pillai R, Westaby S, Shale DJ, Rocker GM. Effects of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor. J Thorac Cardiovasc Surg 1993; 105: 25–30.Google Scholar
Fujiwara T, Seo N, Murayama T, Hirata S, Kawahito K, Kawakami M. Transient rise in serum cytokines during coronary artery bypass graft surgery. Eur Cytokine Netw 1997; 8: 61–66.Google Scholar
Cole DJ, Patel PM, Schell RM, Drummond JC, Osborne TN. Brain ecosanoid levels during temporal focal cerebral ischaemia in rats: a microdialysis study. J Neurosurg Anesthesiol 1993; 5: 41–47.Google Scholar
Kontos MA. Oxygen radicals in cerebral ischaemia. In: Ginsberg MD, Dietrich WD, eds. Cerebovascular Diseases: 16th Princeton Conference. New York: Raven Press, 1989: 365–372.
Ames A, Wright L, Masayoshi K, Thurston J, Majino G. Cerebral ischemia: The no-reflow phenomenon. Am J Pathol 1968; 52: 437–443.Google Scholar
Jean W, Spellman SR, Nussbaum ES, Low WC. Reperfusion injury after focal ischaemia: the role of inflammation and the therapeutic horizon. Neurosurgery 1998; 43: 1382–1396.Google Scholar
Pruefer D, Makowski J, Dahm M, et al. Aprotinin inhibits leukocyte–endothelial cell interactions after hemorrhage and reperfusion. Ann Thorac Surg 2003; 75: 210–215.Google Scholar
Sunamori M, Sultan I, Suzuki A. Effect of aprotinin to improve myocardial viability in myocardial preservation followed by reperfusion. Ann Thorac Surg 1991; 52: 971–978.Google Scholar
Scannell G. Leukocyte responses to hypoxic/ischemic conditions. New Horiz 1996; 4: 179–183.Google Scholar
Chakraborti T, Ghosh SK, Michael JR, Chakraborti S. Role of an aprotinin-sensitive protease in the activation of Ca(2+)-ATPase by superoxide radical (O−2) in microsomes of pulmonary vascular smooth muscle. Biochem J 1996; 317: 885–890.Google Scholar
Nagahiro I, White T, Yano M, et al. Recombinant Kunitz protease inhibitor ameliorates reperfusion injury in rat lung transplantation. Ann Thorac Surg 1998; 65: 66–69.Google Scholar
Tamura K, Manabe T, Imanishi K, et al. Effects of synthetic protease inhibitors on superoxide (O−2), hydrogen peroxide (H2O2) and hydroxyl radical production by human polymorphonuclear leukocytes. Hepato-gastroenterology 1992; 39: 59–61.Google Scholar
Fearon DT, Collins LA. Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures. J Immunol 1983; 130: 370–375.Google Scholar
Barry MC, Wang JH, Kelly CJ, et al. Plasma factors augment neutrophil and endothelial cell activation during aortic surgery. Eur J Vasc Endovasc Surg 1997; 13: 381–387.Google Scholar