Dynamic Changes Of Mouse Cardiac Functions In Early Stage Of Sepsis Induced By CLP

[ABSTRACT] AIM:To investigate the dynamic changes of the cardiac functions in the septic mice in the early stage of sepsis induced by cecal ligation and puncture (CLP).METHODS:Male Kuming mice were used for mimic human sepsis by CLP. Firstly,20 health Kunming mice were used to testify the establishment of bacterial peritonitis by the collection of peritoneal lavage fluid and culture of aerobic and anaerobic bacterium. At each time point of 12 h,24 h,36 h,48 h and 168 h after CLP,2 mice were chosen respectively, then normal saline were injected into the abdominal cavity to wash the peritoneal lavage fluid for 5 minutes for bacterial culture. Meanwhile, the peritoneal lavage fluid from the normal-non-CLP mice was collected with the same procedure for bacterial culture as a negative control. Secondly, we use echocardiography to detect the changes of the cardiac functions in another 100 septic mice in the early stage of sepsis induced by CLP. All the mice were numbered, in order to track its'dynamic changes. Two-D, M-mode and Doppler echocardiography of the hearts were performed before CLP and at time points of 12 h, 24 h,36 h,48 h and 168 h after CLP. Parameters obtained before CLP were treated as the baseline of various cardiac function indexes. The mice survived for 168 h (7 days) were considered as survivals.RESULTS:In the part of the establishment and identification of bacterial peritonitis, the bacterial culture of peritoneal lavage fluid in the control mice was negative. E. coli was detected in all samples of peritoneal lavage fluid extracted from the abdominal cavity of the CLP mice at the time point of 12 h,24 h,36 h,48 h and 168h. Moreover, Proteus mirabilis, Pasteurella and Pseudomonas aeruginosa were also isolated from some samples.The following outcomes were the echocardiographic monitoring of the septic mice at 6 time points. Compared to the baseline values, the blood volumes of the heart return decreased and the heart rate increased both significantly in the early stage of sepsis induced by CLP. Notable compensatory responses of the heart in septic mice were observed, especially the systolic functions, in which, LVEF and LVFS increased by 27% and 44% respectively at the time point of 24 h and return to the baseline at 168 h. However, the diastolic function were weaker than the systolic function. E/A and EDT reduced by 34% and 24% respectively at the time points of 24 h and 36 h after CLP and could not return to its baseline at 168 h. Besides, the left ventricular end-diastolic and end-systolic posterior walls were thickened at the time points of 12 h,24 h and 36 h after CLP, both increased by 16% and 20% at 24 h. LV mass and LV mass corrected were gradually decreased during sepsis and ceased at 168 h. In addition, no difference of serial indexes of the heart functions between 7 day survival group and dead group was observed.CONCLUSION:The strong compensatory response of the cardiac functions, especially the enhanced systolic function is one of the important factors to support the septic animal to survive. Diastolic function of the heart is weakened in the early stage of sepsis and the indexes of diastolic function of 7 day survivals can't return to its baseline. Furthermore, the left ventricular mass also decreases gradually in the early stage to the end point of sepsis, which may be interpreted from the view that apoptosis and necrosis of the cardiomyocytes are increased during sepsis. Protection of the cardiac functions especially the diastolic function is important to survive the septic patients.