Colon Ascendens Stent Peritonitis (CASP) Induces Excessive Inflammation and Systemic Metabolic Dysfunction in a Septic Rat Model

The colon ascendens stent peritonitis (CASP) surgery induces a leakage of gut contents, causing polymicrobial sepsis related to post-operative multiple organ failure and death in surgical patient. To evaluate the effects of GASP on multiple organs, we analyzed the systemic metabolic consequences in liver, kidney, lung, and heart of rats after GASP by employing a combination of metabolomics, clinical chemistry, and biological assays. We found that CASP surgery after 18 h resulted in striking elevations of lipid, amino acids, acetate, choline, PC, and GPC in rat liver together with significant depletion of glucose and glycogen. Marked elevations of organic acids including lactate, acetate, and creatine and amino acids accompanied by decline of glucose, betaine, TMAO, choline metabolites (PC and GPC) nucleotides, and a range of organic osmolytes such as myo-inositol are observed in the kidney of 18 h post-operative rat. Furthermore, 18 h post-operative rats exhibited accumulations of lipid, amino acids, and depletions of taurine, myo-inositol, choline, PC, and GPC and some nucleotides including uridine, inosine, and adenosine in the lung. In addition, significant elevations of some amino acids, uracil, betaine, and choline metabolites, together with depletion of inosine-S'-monophosphate, were only observed in the heart of 18 h post-operative rats. These results provide new insights into pathological consequences of CASP surgery, which are important for timely prognosis of sepsis.