Hostname: page-component-7b7567c8c-mnklg Total loading time: 0 Render date: 2026-11-12T05:28:31.702Z Has data issue: false hasContentIssue false
  • English
  • Français

Abstracts for the British Congenital Cardiac Association Annual Meeting: The Barbican, London, 24–25 November 2005: Winner of the Young Investigator's Prize: Omega-3 fatty acids – pharmacological preconditioning for paediatric cardiac surgical patients

Published online by Cambridge University Press:  01 June 2006

J. McGuinness,
J. Byrne,
A. Hanly,
H. Chen,
C. Condron,
D. Bouchier-Hayes and
J. M. Redmond
J. McGuinness
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
J. Byrne
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
A. Hanly
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
H. Chen
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
C. Condron
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
D. Bouchier-Hayes
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
J. M. Redmond
Affiliation:
Department of Surgery, The Royal College of Surgeons in Ireland
Rights & Permissions [Opens in a new window]

Abstract

Background: Inappropriate systemic inflammatory endothelial and leucocyte activation is a major pathogenic component of post-operative low cardiac output syndrome (LCOS) and associated pulmonary oedema, low urine output, and generalised oedema, in paediatric cardiac surgery. We hypothesised that acute pre-treatment with a parenteral nutrition component omega-3 fatty acid infusion in-vitro, would prevent the pattern of leucocyte and endothelial activation seen in paediatric cardiac surgery through induction of preconditioning. Methods: Endothelial cells were isolated from saphenous vein of 75 adult cardiac surgery patients, grown in monolayers, pre-treated, and then stimulated with either endotoxin (LPS), TNFalpha, or complement C5a (prime mediators of systemic inflammation with paediatric cardiac surgery). Endothelial production of the neutrophil recruiting cytokines IL-6, IL-8, and endothelial expression of the neutrophil adherence receptors E-Selectin, ICAM-1 were assessed. The effects on the inflammatory pro-coagulant response of the endothelium i.e. loss of surface thrombomodulin and production of tissue factor were also examined. Similar methods were employed using isolated peripheral blood neutrophils. The effects on endothelial nuclear translocation of the acute inflammatory transcription factor NFkB and the heat shock protein (HSP72) response were investigated for mechanistic insight. Results: Four hours pre-treatment with the omega-3 infusion prevented endothelial release of neutrophil recruiting cytokines IL-6 and IL-8, also prevented upregulation of endothelial receptors required for neutrophil adherence E-Selectin and ICAM-1, and maintained surface anticoagulant thrombomodulin levels, in response to stimulation with LPS (Table 1) or TNFalpha.

Information

Type
British Congenital Cardiac Association: Abstracts
Information
Cardiology in the Young , Volume 16 , Issue 3 , June 2006, pp. 317 - 318
Copyright
© 2006 Cambridge University Press

Table 1.

The effect of the infusion on adhesion molecule expression was reversible, lasting 18–24 hours. Inflammatory prolongation of neutrophil survival was partially reversed through an increase in apoptotic rate (73% ± 1% of control neutrophils apoptotic at 20 hours versus 77% ± 1% of pre-treated neutrophils, p = 0.03). Pre-treatment produced a more than 2-fold increase in endothelial HSP72 levels (p < 0.05), and reduced nuclear levels of the p65/p50 subunits of NFkB in response to LPS stimulation (2.1 ± 0.2 × 105 relative luminescence units in controls versus 1.3 ± 0.2 × 105 in pre-treated endothelium, p < 0.01). Conclusions: Acute pre-treatment with an omega-3 fatty acid infusion inhibits multiple components of systemic inflammatory activation seen in cardiac surgery. Induction of HSP72 and subsequent reduction of nuclear levels of NFkB, suggest preconditioning mechanisms of inflammatory transcription factor inhibition. This pharmacological strategy may ameliorate paediatric cardiac surgery associated low cardiac output syndrome and it’s sequelae.