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

  • D. Harmon (a1), W. Lan (a2) and G. Shorten (a1)

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.

Copyright

Corresponding author

Correspondence to: Dominic Harmon, Department of Anaesthesia and Intensive Care Medicine, Cork University Hospital, Wilton Road, Cork, Ireland. E-mail: dharmon@indigo.ie; Tel: +353 214 546400 ext 22566; Fax: +353 214 546434

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

  • D. Harmon (a1), W. Lan (a2) and G. Shorten (a1)

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