Caecal ligation and puncture in the rat mimics the pathophysiological changes in human sepsis and causes multi-organ dysfunction

Abstract

Sepsis is a major clinical challenge that is associated with encephalopathy and multi-organ dysfunction. Current therapeutic interventions are relatively ineffective and the development of novel treatments is hampered by the lack of a well-characterised animal model. Therefore, the behavioural, metabolic, physiological and histological changes resulting from 'through and through' caecal ligation and puncture (CLP) in the rat were investigated to determine its suitability as an animal model of human sepsis. CLP resulted in bacteraemia, characterised by the presence of multiple enteric species within 18-20 h. Locomotor activity was reduced within 4 h of CLP and this reduction increased with time. Pyrexia was evident 4-5 h after CLP and was followed by hypothermia beginning 17 h after intervention. CLP resulted in reduced white blood cell and platelet counts and an increased neutrophil: lymphocyte ratio within 18-20 h. It also resulted in decreased blood glucose, but not lactate levels. CLP caused histopathological changes in the cerebral cortex, liver, lungs and vascular system indicative of multi-organ dysfunction. Therefore, CLP in the rat mimics the cardinal clinical features of human sepsis and the subsequent development of multi-organ dysfunction. It appears to be the best available animal model currently available, in which to investigate the underlying pathophysiology of sepsis and identify therapeutic targets.