| Study BackgroundSepsis is the fatal disease that produces a high mortality rate in those who labour under it. The Multiple Organ Dysfunction Syndrome (MODS), caused by sepsis is responsible for the high mortality rate. Heart and kidneys are the important target organs, which are damaged by sepsis, therefore the Cardiorenal Syndromes Type V (CRS Type V) which caused by sepsis become hotspot of research. The mechanisms of CRS are complex. The unstable state of haemodynamics that caused by CRS is a clinical challenge, therefore, it is significant for guiding clinical practice and improving success rate of rescue to explore the haemodynamics that caused by CRS. In addition, new progresses of research reveal that the disorder of immunologic function, excessive activation of inflammation and combined action of multiple inflammatory factors might be the important reason for the unstable haemodynamics. Therefore, modulation of immune response can alleviate the organic injury and enhance success rate of rescue. The mechanism that Systemic Inflammatory Response Syndrome (SIRS) which release a large number of inflammatory mediators (such as TNF-α, IL-1β, IL-6, IFN-γ, IL-8 and so on), and Compensated Anti-inflammatory Response Syndrome(CARS) are coexistent in sepsis. Inflammatory and anti-inflammatory take dominant roles in different phases of sepsis alternately, which lead to Mixed Antagonist Response Syndrome (MARS). A great deal of fluid resuscitation for severe sepsis lead to hypoperfusion, overload and inflammatory in cardiac and kidneys. Moreover, the normal immune system is inhibited, which presented T cells, B cells, dendritic cell and monocyte apoptosis. Due to synthetical factors, heart and kidneys become target organs and interact, which lead to complex physiopathologic change. To maintain stable state of haemodynamics, release inflammatory response and rebuild immune function become the hotspot of sepsis research. Continuous Renal Replacement Therapy (CRRT) can eliminate fluid over load and relieve the cardiac preload and afterload, and eliminate inflammatory factors. Recent researches indicate that it can regulate the immune function. This study induced intra-abdominal infection sepsis models in canines and monitor haemodynamics continuously by advanced methods (Swan-Ganz catheter and PiCCO monitor system). Meanwhile, monitor the change of inflammatory factors such as TNF-α、IL-1β, IL-6, IFN-γ, IL-8 and so on. The sepsis models received fluid resuscitation and were divided into different groups according different types of fluid. Haemodynamics (including capillary leak) were monitored to assess the resuscitative effect. Moreover, collective cases with the sepsis CRS, which received standard treatment and CRRT. To explore the effect of CRRT on haemodynamics, levels of inflammatory factors, extravascular lung water, cardiac function and kidney function. The positive effects were expected and the mechanisms would be expound.Part one The effect of CRRT on canines with sepsis CRS in terms of hemodynamicsObject:To explore the haemodynamics feature of canines with sepsis CRS and the effect of CRRT on haemodynamics.Methods:In this experiment,25 mongrel canines were divided into 5 groups (control group 3, group SHAM 4, group SEP 5, group SEP-R 6 and group SEP-R+RT 7). All of the canines (weight 15+/-2kg) received sedation, a muscle relaxant, had assisted respiration treatment, and central venous catheters, PICCO catheters and Swan-Ganz Catheters were placed and cystostomies were conducted. Besides, the canines in group SEP, group SEP-P and group SEP-R+RT were conducted cecal ligation and puncture (CLP). Otherwise, canines in group SHAM were conducted finding cecum via opening enterocoelia and then the incision were sutured without ligation and incision. By contrast, the enterocoelia of the canines in control group were not opened. All of canines with 12Fr urine catheter which connected with urine measurement systems for calculating urine volume. All of canines received 5% glucose and sodium chloride injection (1.5ml/kg/h) at the beginning. If serve sepsis occured, fluid resuscitation would be conducted (0.9% sodium chloride injection would be injected (30ml/kg/h). It would be stopped immediately when the indexes met the standard of early goal-directed therapy. The canines in group SEP-R+RT received CRRT when they suffered CRS. The haemodynamics parameters were recorded each 6 hours from the beginning.9 canines dead during the experiment and the remainders were executed at the 48th hour.Results:1.The changing of Heart Rate (HR) during the experiment:HR in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, the HR in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.01), the HR in the SEP-R+RT group was lower than the SEP-R group when the experiment finished (P=0.025).2.The changing of CVP during the experiment:CVP in all of the groups were compared and found no significant difference (P>0.05).3.The changing of MAP during the experiment:MAP in the groups of CLP decreased overtime. Compared with the SEP group, MAP in the groups of Control and SHAM significantly increased (P=0.000, P=0.000), and compared with the SEP-R group, MAP in the groups of Control and SHAM significantly increased (P=0.001, P=0.001), and the MAP in the SEP-R+RT group was higher than it in the groups of SEP and SEP-R (P=0.000, P=0.005) when the experiment was finished.4.The changing of SV during the experiment:SV in the groups of CLP decreased overtime. Compared with the groups of Control and SHAM, SV in the groups of SEP and SEP-R significantly decreased (P<0.001); and compared with the SEP group, SV in the groups of SEP-R and SEP-R +RT significantly decreased (P=0.002, P=0.000) when the experiment was finished.5.The changing of SVV during the experiment:SVV in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, SVV in the groups of SEP, SEP-R and SEP-R+RT significantly increased (P<0.001); and compared with the SEP group, SVV in the groups of SEP-R and SEP-R+RT significantly increased (P=0.000, P=0.000) when the experiment was finished.6.The changing of GEF during the experiment:GEF in the groups of CLP decreased overtime. Compared with the groups of Control and SHAM, GEF in the groups of SEP, SEP-R and SEP-R+RT significantly decreased (P<0.01); compared with the SEP group, GEF in the groups of SEP-R and SEP-R+RT significantly increased (P=0.000, P=0.000) when the experiment was finished.7.The changing of GEDI during the experiment:GEDI in the groups of CLP decreased overtime. Compared with the groups of Control and SHAM, GEDI in the groups of SEP,SEP-R and SEP-R+RT significantly decreased (P<0.01);compared with the SEP group, GEDI in the groups of SEP-R and SEP-R+RT significantly increased (P=0.021, P=0.000),and it in the SEP-R group was lower than that of the SEP-R+RT group (P=0.017) when the experiment was finished.8.The changing of CI during the experiment:CI in the groups of CLP decreased overtime. Compared with the other groups, the CI in the SEP group significantly decreased(P<0.05); Compared with the Control group, the CI in the groups of SEP-R and SEP-R+RT significantly decreased (P=0.009, P=0.004) when the experiment was finished.9.The changing of SVRI during the experiment:SVRI in the groups of CLP firstly increased and then decreased overtime. Compared with the groups of Control and SHAM, SVRI in the groups of SEP-R and SEP-R+RT significantly decreased (P<0.01); SVRI in the SEP-R+RT group was higher than that of SEP-R group(P=0.006) when the experiment was finished.lO.The changing of ELWI during the experiment:ELWI in the groups of CLP increased overtime. Compared with the groups of SEP-R and SEP-R+RT, ELWI in the groups of SEP, Control and SHAM significantly decreased (P<0.001); ELWI in the SEP-R+RT group was lower than that of SEP-R group(P=0.018) when the experiment was finished.11.The changing of PVPI during the experiment:PVPI in the groups of CLP increased in the late of the experiment. Compared with the groups of SEP-R and SEP-R+RT, ELWI in the groups of SEP, Control and SHAM significantly decreased (P<0.05); when the experiment was at the time of 36h.12.The changing of PAWP during the experiment:PAWP in the groups of SEP-R and SEP-R+RT increased in the late of the experiment. Compared with the Control group, the PAWP in the groups of SEP-R and SEP-R+RT significantly increased (P=0.001, P=0.006); Compared with the SEP-R+RT group, the PAWP in the groups of SEP-R significantly increased (P=0.027) when the experiment was in the point of 36h.13.The changing of Lac during the experiment:Lac in the groups of CLP increased overtime. Compared with the groups of Control and SHAM,Lac in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.01); Compared with the SEP-R group,Lac in the groups of SEP and SEP-R+RT significantly increased (P=0.011, P=0.000);it was lower in the SEP-R+RT group than that of SEP group (P=0.000) when the experiment was finished.14.The changing of SVO2% during the experiment:SVO2% in the groups of CLP decreased overtime. Compared with the groups of Control and SHAM, SVO2% in the groups of SEP,SEP-R and SEP-R+RT significantly decreased (P<0.001) when the experiment was finished.15.The changing of Cr during the experiment:Cr in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, Cr in the groups of SEP,SEP-R significantly decreased (P<0.01), Compared with the SEP-R+RT group, Cr in the groups of SEP,SEP-R significantly increased(P=0.000, P=0.000), when the experiment was at the point of 42h.16.The changing of Urine Output during the experiment:Urine Output in the groups of CLP decreased overtime. Compared with the groups of Control and SHAM, Urine Output in the groups of SEP,SEP-R and SEP-R+RT significantly decreased (P<0.01)when the experiment was in 42-48h.17.The changing of NT-proBNP during the experiment:NT-proBNP in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, NT-proBNP in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.05)when the experiment finished.18. The changing of cTNT during the experiment:cTNT in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, cTNT in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.01)when the experiment finished.Conclusion:1. The haemodynamics characteristics of canines with sepsis CRS induced by CLP were low volume, meanwhile cardiac index and SVRI increased in early phase and decreased in late phase, which caused microcirculation disturbance. In addition, fluid resuscitation cannot improve low volume and cardiac index (CI) efficiently, and it would lead to the increasing of EVLW.2. CRRT can improve the hemodynamic states of these canines. It improved renal function and microcirculation effectively. It is benefit for increasing SVRI and CI, and protecting renal function.Part two The effect of Continuous renal replacement therapy on inflammatory mediators of cardiorenal syndrome canines induced by sepsisObject:To observe The effect of CRRT on inflammatory mediators of cardiorenal syndrome canines induced by sepsis.Method:The same with the part one, from Oh to 48h, Arterial blood was drawn to analyze the level of IL-6,IL-10 and TNF-α.Results:1.The changing of TNF-α during the experiment:TNF-α in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, TNF-α in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.05); Compared with the SEP-R+RT group, TNF-α in the groups of SEP,SEP-R significantly increased(P=0.000,.P=0.045), when the experiment finished.2.The changing of IL-6 during the experiment:IL-6 in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, IL-6 in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.05); Compared with the SEP-R+RT group, IL-6 in the SEP-R group significantly increased(P=0.020), when the experiment was finished.3.The changing of IL-10 during the experiment:IL-10 in the groups of CLP increased overtime. Compared with the groups of Control and SHAM, IL-10 in the groups of SEP,SEP-R and SEP-R+RT significantly increased (P<0.001); Compared with the SEP-R+RT group, IL-10in the groups of SEP,SEP-R increased, when the experiment was finished.Conclusion:1. In the Canines with sepstic CRS induced by CLP, TNF-α、IL-6 and IL-10 in serum increased evidently.2. The CRRT can decrease the level of TNF-α、IL-6 and enhance IL-10 in these Canines. It means CRRT has a protective effect on CRS and sepsis.Part 3 The effect of Continuous renal replacement therapy on peripheral T lymphocytes apoptosis of cardiorenal syndrome canines induced by sepsisObject:To observe the effect of CRRT on peripheral T lymphocytes apoptosis of cardiorenal syndrome canines induced by sepsis.Method:The same with the part one, at the beginning and the end of the experiment, 2 ml Arterial blood was drawn to analyze T lymphocytes apoptosis by the Flow Cytometry.Results:1.The changing of Lym count during the experiment:At the beginning of the experiment, the Lym count in all of the groups has no significant difference, but in the end of the experiment, the Lym counts in the groups of SEP,SEP-R and SEP-R+RT were lower than that of the in the groups of Control and SHAM(P<0.05), the Lym counts in the groups of SEP,SEP-R and SEP-R+RT were lower when they were compared with their beginning respectively (P=0.002, P=0.000, P=0.000).2.The changing of T Lym apoptosis rate in the peripheral during the experiment: At the beginning of the experiment, T Lym apoptosis rate in all of the groups has no significant difference, but in the end of the experiment, the T Lym apoptosis rate in the groups of SEP,SEP-R and SEP-R+RT was higher than that of the in the groups of Control and SHAM(P<0.05), the T Lym apoptosis rate in the groups of SEP,SEP-R and SEP-R+RT was higher when they were compared with their beginning respectively (P=0.002,P=0.000,P=0.000).Conclusion:1.It is obvious that the immunologic function was suppressed, the count of peripheral blood T cells decreased, and apoptosis of T cells increased for the canines with septic CRS induced by CLP.2. CRRT can decrease apoptosis of peripheral blood T cells and improve immunologic function. |
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