Caecal Ligation and Puncture Develops Time Dependent Progression of Sepsis with Multiple Organs Damage and Vascular Dysfunctions in Mice

Abstract

Sepsis is a dysregulated systemic inflammatory response syndrome that affects multiple organs. However, its effect on vital organs during different phases of sepsis is lacking. Present study was carried out to establish the time dependent changes in the vital organs during different phases of sepsis. Sepsis was induced by caecal ligation and puncture in mice. Sepsis significantly reduced RBC, Hb and WBC counts during both the phases whereas neutrophil count was increased during early phase. There was also a marked fall in lymphocyte count during late phase of sepsis which is an indicative of immunosuppressive state. Significant rise in the plasma ALT, AST, BUN and creatinine levels during early and late phases of sepsis were suggestive of liver and kidney dysfunctions which were further substantiated by histopathological examinations of these vital organs. Sepsis also produced a state of hypoproteinaemia with significant reduction in plasma albumin level. Significant progressive attenuation of vascular reactivity to nor-adrenaline and endothelial relaxation to acetylcholine were also observed in early to late phases of sepsis. However, sodium-nitroprusside-induced endothelium-independent relaxation was unaltered in both early ‘as well as late phase of sepsis. Histopathological examination of lungs, heart and intestine showed progressive degenerative changes which were more prominent with progression from early to late phase of sepsis. Based on the findings of the present study, it may be inferred that caecal ligation and puncture produces time-dependent progression of sepsis in mice affecting multiple organs.