Extracorporeal membrane oxygenation for severe systemic inflammatory response : development of a rabbit model

Hypothesis: ECMO is an acceptable supportive therapy for patients with severe SIRS despite triggering haematic response.;Objectives: To develop a reliable and reproducible animal model of SIRS to investigate strategies for reducing the haematic response.;Materials and Methods: Literature review: (I) The Systemic Thrombo-inflammatory Pathway (STIP). (II) The haematic response. Clinical studies: (I) Institutional review of ECMO for severe SIRS. (II) Comparative review of oxygenators performance. In-vivo studies: Animal experiments, (I) Development of a rabbit model of graded SIRS. (II) Dose response relationship between administered intravenous endotoxin and fatal Multi-organ Dysfunction Syndrome (MODS). (III) Inter-individual variation amongst rabbits receiving a lethal dose of endotoxin. In-vitro studies: Evaluation of the cellular and biochemical components of STIP in rabbits. (I) Development of rabbit ELISA. (II) Determination of the normal range, dose response and inter-individual variation. (III) Immunohistochemical evaluation of endotoxin induced lung injury. (IV) Dose related oxidative stress and DNA damage and (V) apoptosis in rabbit lung.;Results: There is a reciprocal relationship between graded SIRS and the outcome of ECMO. There is a linear relationship between the dose of endotoxin and the development of graded SIRS in rabbits. Significant DNA homology and cross-reactivity exists between humans and rabbits making this a useful model for immune experimentation.;Conclusions: ECMO is superior to conventional ICU management in selected groups of patients. New oxygenator technology has significantly reduced the haematic response to ECMO, however it has failed to influence survival. Cellular components such as neutrophils play a central role in SIRS activation, however thrombin appears to be the common biochemical component for feedback escalation and progression of severe SIRS to MODS.