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Title: Inflammatory changes during cardiopulmonary bypass surgery and their modulation by modified ultrafiltration in children
Author: El-Habbal, Magdi Hassan Ali
ISNI:       0000 0001 3442 810X
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1998
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Children who undergo cardiopulmonary bypass (CPB) for heart surgery develop identifiable tissue oedema which may be caused by inflammatory responses to CPB. We investigated these responses in a series of in vitro and in vivo studies. In vitro, we tested in mock CPB (n = 15) using donor blood the effects of circulation, stasis and temperature variation. In vivo, we conducted a randomised trial of modified ultrafiltration (MUF) in children (n = 20) undergoing surgical repair of ventricular septal defect examining the changes in these responses and total body water (TBW). Expressions of neutrophil adhesion molecules CD11b and L-selectin were assayed using immunefluorescence and flow cytometry. Serum interleukin-8 (IL8), interleukin-6 (IL6), tumour necrosis factor-alpha (TNF-a), leukocyte elastase and terminal complement complex (TCC) were determined using enzyme linked immunosorbent assay. TBW was measured by using bioelectrical impedance. In vitro, mock CPB caused up-regulation of CD11b, down-regulation of L- selectin and increased serum IL-8, TNF-a, leukocyte elastase and TCC. These changes were higher in circulation than in stasis. Cooling decreased and rewarming increased, up-regulation of CD11b, down-regulation of L-selectin and serum IL-8. In vivo, MUF improved patients' haemodynamic parameters compared to control. TBW and IL 8 peaked at 3 - 6 and 1 hour after CPB, respectively. The rise of TBW in the MUF group was less than the control (p 0.001). This was associated with reduction of serum IL-8, CD11b and L-selectin in the MUF treated patients. MUF did not cause further increase of TCC, leukocyte elastase, IL-6 and TNF-a. Thus, CPB preparations (circulation and temperature variations) stimulated neutrophil adhesion molecules and cytokine release. MUF reduced TBW and serum IL-8. We speculate that modulation of neutrophil activation, e.g. by using monoclonal antibodies or modified ultrafiltration, may reduce the inflammatory responses to CPB and may reduce patient morbidity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine