| Backgroud:sepsis is a systemic inflamatory response syndrome triggered by infection, severe sepsis is among the most important causes of morbidity and mortality in patients admitted to the intensive care unit. The yearly incidence of severe sepsis is increasing and has recently been reported as 132 per 100000 population, with a mortality approaching 50%. The incidence of sepsis is disproportionately increased in the elderly, and age is an independent predictor of survival. despite continuing progress in the development of antibiotics and other supportive care therapies, sepsis remains a leading cause of high morbidity and mortality in the intensive care unit.the outcome of sepsis has not improved significantly in the past years. perhaps the treatment combining Modern Medicine and Traditional Chinese Medicine is a potential way to solve the problem. Recent study recognize the importance of sepsis induced myocardial depression(SMD) is an important phenomenon. We proved the method of benefiting Qi and promoting blood circulation(tongguan capsale) could improve the cardiac function caused by coronary heart disease in the clinical and experimental research. so we think the method of benefiting Qi and promoting blood circulation(tongguan capsale) can improve the prognosis of the sepsis by improve the cardiac function in sepsis patients. In order to confirm this hypothesis, we conduct a clinical and experimental research.To evaluate the clinical value of SMD in sepsis, and to investigate the clinical effect and mechanism of action of the method of Benefiting Qi and Promoting Blood Circulation (tongguan capsale) in the patients with SMD at the same time. Our study including two part, one is clinical study, the other is experimental study.Part one:clinical studySubject and methods: our study was performed at the second Affiliated Hospital of Guangzhou University of TCM. From April 2007 to November 2010 Patients admitted to the intensive care unit(ICU), who fulfilled with ACCP/SCCM Consensus conference criteria of severe sepsis were enrolled in this prospective,single blind,random trial. In this study, we divided into treatment group and controlled group, A was treatment group, has 29 patinets, B was controlled group, has 28 patients. all patients accepted conventional therapy, A group treated with Chinese medicine tong guan capsule,3 grains, tid.On admission(the first day), on days 7 after stars of treatment, Acute Physiology and Chronic Health Evaluation(APACHEII) scores were also recorded。We examined the cardiac function by echocardiography technique at the two time points, then 10 ml Peripheral blood samples were obtained from patients. The serum concentrations of TNF-α,IL-6 were measured means of ELISA, CTnI,BNP,CK-MB were measured by laboratory of our hospital.Result:1,The survival rate:The survival rate in 28 days was 75.9%(22/29) in group A, while that of in group B was71.4%(20/28); The survival rate in 90 days was 48.3%(14/29) in group A, while that of in group B was 39.3%(11/28), There was not a significant difference between two groups in two time points。2,The APACHE II score:Before treatment there is no significant difference between group A with group B. Scores had a decrease trend declined in two groups during the treatment (P＜0.05). On day 7, compared with group B, scores declined significantly in group A (P＜0.05)3,The Changes of cytokines:on admission, Patients with severe sepsis had Significantly higher concentrations of all measured cytokines compared to normal value, and there is no significant difference between the two group. on day 7, TNF-a,IL-6 levels in group A and B decreased significantly (P＜0.05). The difference of IL-6 levels between A and B group were significant (P＜0.05) on day 7.4,The changes of cardiac enzymes and BNP:on admission, Patients with severe sepsis had significantly higher concentrations of CTnI and BNP compared to normal value, and there is no significant difference between the two group. on day 7, CTnI and BNP levels in group A and B decreased significantly (P＜0.05). The difference of CTnI and BNP levels between A and B group were significant (P＜0.05) on day 7. On day 1 and 7, the concentration of CK-MB is normal in two groups, and there is no significant difference between the two groups on day 7.5,The changes of cardiac function by echocardiography technique:on day 1, there is no significant difference between the two group about EF,E/A,LVEDVI,LVESVI on day 7, E/A and LVEDVI in group A and B decreased significantly (P＜0.01). The difference of EF,E/A and LVEDVI between A and B group were significant (P＜0.05,P＜0.05,P＜0.01 respectively) on day 7.6,the changes of center venous pressure (CVP):on admission, Patients had lower CVP, and there is no significant difference between the two group. on day 1, CVP increased significantly (P＜0.01) after fluid resuscitation in the two group. On day 3, CVP decreased in both groups, there is a significant difference between the two group(P＜0.05). On day 7, CVP decreased sequentially in both groups, there is a significant difference between the two group(P＜0.05). The difference of CTnI and BNP levels between A and B group were significant (P<0.01).Conclusion:Clinical features of SMD is impaired cardiac diastolic function;The method of Benefiting Qi and Promoting Blood Circulation (tongguan capsale) could improve the curative effect and degrade APACHE II score in the patients with sepsis. The method of Benefiting Qi and Promoting Blood Circulation could improve the cardiac diastolic function measured by echocardiography technique, decreased the serum CTnI and BNP levels and CVP after fluid resuscitation. The possible mechanism may be associated with the decrease the serum IL-6 levels.Part two:Experimental researchSubject and methods:To prepare the septic animal model with cecal ligation and puncture (CLP), 120 male SD rats were randomly divided into three groups:Sham operation group (n=40), CLP group(n=40), treatment group(n= 40)。All groups being further divided into 12h,24h,48h,72h,168h subgroups。Each subgroup had eight rats.168h subgroups only observed their mortality rate.All rats were measured left ventricular systolic pressure(LVSP), left ventricular pressure maximal rate of fall(-dp/dtmax), left ventricular pressure maximal rate of rise(+dp/dtmax) through left common carotid artery after anesth;detected the changes of CTnI,TNF-αand IL-6 in blood serum。observed damage of cadiocyte using microscope and electron microscope.Result:1,The mortality:The mortality of animals were observed within 7 days after operation, the mortality of CLP group were 62%(5/8), the mortality of treatment group were 38%(3/8);the all mortality of CLP group were 45%(18/40), the all mortality of treatment group were 25%(10/40), then there had a trend to decreased mortality treated with tongguan capsule (X2=3.516, P=0.061).2,The hemodynamic:LVSP, of sepsis rats obviously decreased at 12 hours after CLP, at 24 hours reached minimum, significantly less than sham operation group(p＜0.01). After that, them begin to rise, but+dp/dtmax and-dp/dtmax still less than that of sham operation group. The difference of LVSP,+dp/dtmax and-dp/dtmax between CLP group and treatment group were significant at 24hours and 48hours after CLP. The difference of+dp/dtmax and-dp/dtmax between CLP group and treatment group were significant) at 72 hours after CLP.3,The serum levels of cTnI:The serum levels of cTnI in sepsis rats obviously raised at 12 hours after CLP, reached to peak value(1.489ng/ml)at 48 hours point, after that started to drop down, but still exceed sham operation group(p＜0.01). There was a significant difference between the CLP group and treatment group in two time points (24h,48h,72h)。4,The inflammatory factor:The level of TNF-αand IL-6 in serum obviously rised, at 24 hours after CLP reached maximum, and there was a significant difference between the CLP group and treatment group at 24 hours and 48 hours after CLP.5,pathomorphological change:the evaluation criterion of SMD through light microscope including:the cytoclasis and cellular degeneration of myocardial cell,and the definition of transverse striation,coronary arterial hyperemia,the extent of inflammatory reaction of interstitial substance。the evaluation criterion of SMD through electron microscope including:the structural integrity of cell nucleus,the definition of Z line,the number of mitochondria, the hyperplasia of interstitial fibers。The myocardial damage in septic rats was alleviated after treatment assessed by light microscope and electron microscope。Research conclusion:The method of Benefiting Qi and Promoting Blood Circulation could improve the cardiac diastolic and systolic function of sepsis rats measured by invasive homodynamic monitoring, and it could decrease the serum CTnI. we inferred this effect may be associated with the decrease the serum inflammatory factor including TNF-a,IL-6 levels.
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