| AIM:To characterize the systolic functions of heart, hemoperfusion of coelio-organs and circulating cytokines in the high mortality stage of sepsis in mice. METHODS:1. Health male Kunming mice were used in the study. Cecal ligation and puncture (CLP) were performed to mimic human sepsis. The mice survived for 7 d were considered as survivals.2.100 mice were used in the study. The techniques of 2D, M-mode and pulse-wave Doppler were applied to evaluate the systolic functions of the heart and the blood flow of abdominal aorta, right renal artery and portal vein before CLP as the baseline and at time points of 12 h,24 h,36 h, 48 h and 60 h after CLP. All data were compared with the baseline values. All parameters were measured and calculated by special software.3. Eighty mice were randomly allocated to CLP group (n=77) or a control group (n=3). In CLP group,6 mice were chosen respectively and sacrificed to collect serum samples at time points of 12 h,24 h,36 h,48 h,60 h and 168 h after CLP. The control mice were also sacrificed to collect serum samples at the time point of 0 h. The technique of Luminex xMAP was used to evaluate the levels of TNF-α, IL-1β, IL-6, IFN-γ, IL-10 and G-CSF.RESULTS:1. The stroke volume (SV) of the CLP mice continuously decreased during the high mortality stage of sepsis. Due to the compensatory responses of the systolic functions, cardiac output (CO) of the CLP mice remained in normal or hyper-dynamic levels. However, the cardiac compensations were depressed later, and the CO decreased apparently at 60 h. In addition, the data from survival group and death group were compared and the systolic dysfunctions were closely related with the deaths of the septic mice. No difference of the index at baseline between survival group and death group was observed.2. The levels of blood flow in abdominal aorta were increased first and then decreased. Resistive index (RI) and pulsatility index (PI) of abdominal aorta began to increase at the time point of 24 h after CLP. Blood flow of right renal artery showed a significant decline from the beginning to the end of our observation. No significant difference of the right arteriorenal RI and PI was observed. Portal venous flow increased significantly at 12 h, and decreased at 24 h after CLP. Congestion index of the portal vein were distinctly increased from 12 h to the end of the observation. No difference of the index at baseline and the hemodynamic functions between survival group and dead group were observed.3. G-CSF levels in serum increased significantly at 24 h,36 h and 48 h after CLP and reached a significantly high level (10,000 pg/mL). IL-6 was characteristic of a sharp peak before 24 h, with the maximal value of about 1,500 pg/mL. The levels of other cytokines, including TNF-α,IL-1β,IFN-γ,IL-10, were significantly lower than G-CSF and I1-6, and fluctuated within 100pg/mLCONCLUSION:In the high mortality stage of sepsis, strong compensatory responses of systolic functions take place in CLP mice to maintain the systemic circulation. The hemodynamic s of coelio-organs in high mortality stage of septic mice shows specific changes. The levels of blood flow in abdominal aorta and portal vein are increased at first and then decreased, and the circulatory resistances are higher than normal. However, the renal blood flow remains in low level. The concentration of circulatory cytokines shows three different trends:the level of G-CSF is significant high, and IL-6 keeps in a moderate level, while TNF-α, IL-1β, IFN-γand IL-10 are at very low concentrations. The above results indicate important roles in evaluating the mechanism of sepsis. |
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