No CrossRef data available.
Published online by Cambridge University Press: 01 June 2006
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.