The Effect Of Continuous Blood Purification On Plasma Vasoactive Substances In Piglets With Endotoxic Shock

Preface:Sepsis is one of the severe complications in critically ill patients with trauma,burn, shock,infection or major operations,and is also the important inducement of septic shock and multiple organ dysfunction syndrome(MODS).One of the major problems is the uncontrollable "mediator disease" resulted from a release of a large number of cascaded inflammatory mediators.There is a high mortality of 30-70%and also a high morbidity in severe sepsis.There is an urgent need for new techniques and methods to treat sepsis.Continuous blood purification(CBP) is an emerging therapeutic technique which was developed in recent 30 years.The effect of CBP for sepsis was satisfactory in recent years. It can improve cardiovascular function and respiratory function quickly and can stable hemodynamics significantly.The main mechanism of CBP for sepsis is it can decrease induced inflammatory-anti inflammatory response intensity.But its mechanism improving cardiovascular function is still unclear.It has been known that in normal physiological state the L-Arginine/NO system,sympathetic nervous system and endothelin(ET) system are the main systems to keep basic vascular tension.At this moment there are few reports that studied whether CBP will affect the balance between these three systems in sepsis,and promote the stability of hemodynamics and improve the cardiovascular function accordingly. The results of these reports were not consistent.In the pediatric population the relevant research reports are even less.Objectives:To main objectives are to observe the effect of CBP on hemodynamics and plasma vasoactive substances in piglets with endotoxic shock and to explore the mechanism improving cardiovascular function and stabling hemodynamics of CBP.Methods:17 healthy piglets were randomly assigned into three groups:normal control group(NCON)(n=5),endotoxic shock control group(CON)(n=6),CBP treatment group(n=6). E.Coli endotoxin O111:B4 was injected into the piglets in the CON and CBP group to induce endotoxic shock.Only fluid containing NaCl 0.9%and ringer's solution was used during the experiments.One hour after injection of endotoxin,the models were established and CBP was applied to the CBP group.These models were observed for 5 hours.All other treatments were the same in the CON and CBP group.The piglets of the NCON group were infused with saline by 10ml/kg.h and observed for 6 hours.We recorded the clinical parameters of SIRS(BT,HR,RR)and circulatory parameters(MABP,HR,PCCI,SVRI, SVI)at baseline(marked T0),onset of endotoxic shock(marked T),an hour,three hours and five hours after endotoxic shock(marked T1,T3,T5).At the same time the blood samples were taken to detect the level of plasma vasoactive substances(DA,ET-1 and NOS). Statistical analysis for the data was performed using the Statview 7.0 software.Results:All the endotoxic shock models were established successfully within 1h after injection of endotoxin.1.Changes of clinical parameters of SIRS:After endotoxin injection,the BT,RR and HR increased in the CON and CBP group.In the CON group,these parameters continued to rise and stabilized at a higher level gradually.In the CBP group,the clinical parameters gradually normalized after the treatment with CBP.At T5,there is a significant difference between the CON and CBP group(P＜0.05).2.Changes of circulatory parameters:In the CON and CBP group,the HR increased and MABP,PCCI,SVRI,SVI decreased after endotoxin injection.In the CON group,the HR continued to rise and stabilized at a higher level and the MABP,PCCI,SVRI and SVI continued to drop and stabilized at a lower level gradually.In the CBP group,the HR normalized gradually after the treatment with CBP.At T5,the HR was significantly different in the CON and the CBP group(P＜0.05).In the CBP group,the PCCI increased and at T5,it was significantly higher than in the CON group(P＜0.05). SVRI and MABP increased and they were significantly higher than in the CON group(P＜0.05)at T3 and T5.SVI increased and it was significantly higher than in CON group(P＜0.05)at T1,T3 and T5.3.Changes of the level of plasma vasoactive substances:After endotoxin injection,DA, ET-1 and NOS increased in the CON and the CBP group.In the CON group,DA concentration was significantly higher than in the NCON group(P＜0.05)at T3 and T5. The ET-1 concentration was also significantly higher than in the NCON group(P＜0.05)at T5.NOS activity dramatically increased and it was significantly higher compared to the NCON group(P＜0.05)at T1,T3 and T5.In the CBP group,DA and ET-1 concentration further increased after the treatment with CBP and they were significantly higher compared to the CON group(P＜0.05)at T5.An hour after CBP treatment,NOS activity started to decrease.It was significantly lower than in the CON group(P＜0.05)at T1,T3 and T5.4.Correlation between changes in the level of plasma vasoactive substances and changes in the hemodynamics:In the CON group,hemodynamic changes after endotoxin injection were correlated to the changes of the plasma level of DA,ET-1 and NOS.In the CBP group,the state of hemodynamics improved significantly after CBP treatment. There is a significant correlation between hemodynamic improvement and the changes in the level ofDA,ET-1 and NOS(r＞0.9,P＜0.05).Conclusions:1.Cardiac function decreased and the peripheral vascular resistance changed at the time when endotoxic shock was induced by lipopolysacharides(LPS).Continuous blood purification improved the cardiovascular function significantly.2.The CBP treatment affected the L-Arginine/NO system,sympathetic nervous system and ET system,measured in plasma level changes of vasoactive substances.DA and ET-1 concentration increased and NOS activity decreased significantly.These changes were significantly correlated to the improvement of cardiovascular function.