Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-23T17:24:03.426Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access

Extract

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

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