Date of Award

2010

Document type

Thesis

Degree Name

MD (Medical Doctor)

First Supervisor

Professor J. M. Redmond

Second Supervisor

Dr Jonathan McGuinness

Keywords

Fatty Acids, Omega 3, Thoracic Surgery

Abstract

Advances in paediatric cardiac surgical techniques over the past two decades have resulted in increasingly successful complex corrective procedures, which are frequently performed on younger, more vulnerable infants. A degree of cardiac, pulmonary, renal and cerebral dysfunction is frequently seen post-operatively; this ranges in severity, but can in some progress to multiple organ failure. The exact mechanisms, pattern and timing of the post operative organ dysfunction following paediatric cardiac surgery has not been fully elucidated, however it is now appreciated that the systemic inflammatory response syndrome, induced by a number of factors present in cardiac surgery, has a central role. To date, much research has been undertaken in developing strategies to attenuate the SIRS; however, results are conflicting and none have consistently shown a benefit in clinical practice. Omega-3 fatty acids have been shown to have anti-inflammatory, anti-infarct and antiarrhythrnic properties. Multiple pathways for these effects have been recognized: a reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines; an increase in the omega-3/omega-6 fatty acid ratio in cell membranes; an attenuation of the period of post-operative immunosuppression; and the production of resolvins and protectins, important in the resolution of inflammation. The aim of this research therefore was two-fold: to determine the mechanisms involved in the injury induced by cardiac surgery, and to determine if omega-3 fatty acids, given in a clinically approved formulation, could attenuate the SIRS and produce beneficial clinical effects in a juvenile piglet model of cardiopulmonary bypass and circulatory arrest. The results obtained demonstrated a pattern of cardiac and pulmonary injury attributable to the SIRS. Renal injury occurred earlier and was not associated with SIRS. Omega-3 pre-treatment resulted in an attenuation of the systemic inflammatory response, as measured by cytokines and eicosanoids, and did demonstrate trends towards improved cardiopulmonary function. This research provides a basis for further study into the mechanisms of post cardiac surgical organ injury, and also the attenuation of the SIRS with omega-3 pretreatment in the clinical arena.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

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Comments

A thesis presented for the award of MD to the Royal College of Surgeons in Ireland, 2010.

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