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Experimental Study Of Extracorporeal Membrane Oxygenation Combined Continuous Renal Replacement Therapy Effects On The Kidney

Posted on:2015-05-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y M HuFull Text:PDF
GTID:1364330491959750Subject:Surgery
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ECMO(Extracorporeal membrane oxygenation,ECMO)is a novel mechanical device and technique which can utilize respiratory and circulatory supporting,it can not only provide a longer life support for patients with severe respiratory and circulatory failure,but also create conditions for cardiopulmonary resuscitation.Currently,ECMO has become an essential tool for treatment of acute circulatory and respiratory failure.However,compared with cardiopulmonary bypass technique,ECMO can support treatment for a longer time,more organs.Therefore,it have the higher incidence of complications.And because ECMO running is not under physiological condition,it may effort various organs function during the ECMO treatment.Once serious complication appearing,it often leads to failure of their treatment.Kidney is one of the vital organs by ECMO affected,and acute kidney injury is one of the complications of ECMO.On the clinical,Poor prognosis of acute renal failure after ECMO treatment have been reported.And many studies have shown that the incidence of patients who received AKI is higher than non-received.In our early research,we observed that it occurs ECMO related systemic immune inflammatory reaction,however,it can remove inflammatory mediators,reduce pulmonary edema,pulmonary parenchyma protection after ECMO combined CRRT.Continuous renal replacement therapy(continuous renal replacement therapy,CRRT)provides important survival in vivo environment by their homodynamic stability,sustaining and stable control of azotemia and water-salt metabolism,removing toxins from the body and keeping out inflammatory factors,ensuring nutritional supplements etc when it treat critically ill patients.CRRT superiority lies in:1,Hemodynamically stable:CRRT sustained ultra filtration on solute clearance is slower changes gradually in plasma osmolality crystals,smaller change in extra cellular fluid volume,better in filter biocompatibility,slower flow in vitro,less impact on the cycle.2,the molecules and inflammatory mediators removal:CRRT higher membrane permeability can remove less than 40000 to 50000 Dalton molecular substances and inflammatory mediators,and it have inflammatory mediators adsorption effection.3,internal environment stable:CRRT can quickly adjust the electrolyte and acid-base status.In summary,CRRT can hopefully solve patients receiving renal injury caused by ECMO and it can play their respective advantages when combined ECMO and CRRTAlthough large of ECMO and CRRT research have been found on the clinical,acute kidney injury of basic and systems research,especially its specific mechanism are still depict.The purpose of our study focus on its mechanical research.On the one hand,ECMO treatment can improve systemic oxygenation,excluded CO2 protective effect on the kidneys,on the other hand,ECMO treatment may have some adverse effects on the kidneys in systemic immune inflammatory response.Meanwhile,we evaluate ECMO treatment by more systematic and comprehensive,and assess effects on the kidneys,when ECMO combined CRRT treatment.In this study,we divided animal into two parts,one is the normal piglet,the other part is a piglet model of post-traumatic ARDS.Firstly,post-traumatic severe ARDS model is closer to the need of clinical treatment;secondly,because the model itself after ischemia and reperfusion in the presence of acute renal injury in the process,we can compare between ECMO alone with ECMO combined CRRT treatment is produced by the kidneys of animals affected In the present study,our research team had successfully completed the CRRT and ECMO parallel manner and evaluated the animal experiments in vitro.On this basis,we adopted several aspects of the different groups at each time point of renal function and inflammation research,histologic kidney,the kidney oxidative stress research,analyzed effects on the kidneys of normal piglets using contrast VV ECMO alone and VV ECMO combined CRRT.Part ? Effect of Extracorporeal Membrane Oxygenation and combined with continued renal replacement therapy on the kidney in a healthy piglet modelStudy?:Effect of Extracorporeal Membrane Oxygenation on the kidney in a healthy piglet modelObjective:On the one hand,ECMO treatment can improve systemic oxygenation,excluded CO2 protective effect on the kidneys,but on the other hand ECMO treatment may have some adverse effects on the kidneys in systemic immune inflammatory response.During VV ECMO running,the renal change in the basic research is scared.In this study,using low tidal volume ventilation in normal piglets,we research the effect of VV ECMO treatment itself on the kidney in multi-aspects including renal tissue inflammatory response,renal function,renal morphology,renal oxidative stress;meanwhile,we explore the associated mechanism.Methods:18 healthy piglets in low tidal volume ventilation were randomly divided into three groups:control group;sham group venous catheter;VV ECMO group;They underwent systemic anticoagulation and observed for 24 hours.Conventional homodynamic changes recorded in general;detected Oh,2h,6h,12h,24h free hemoglobin blood samples(Free Serum Hemoglobin,FHb)level;detected Oh,2h,6h,12h,24h serum urea nitrogen(blood urea nitrogen,BUN)and serum creatinine(Serum creatinine,Scr)and other general changes in renal function;.use NGAL and CysC as early detection of acute kidney injury;detect IL-1?,IL-6,TNF-? and the expression;Kidney were observed changes in gross morphology and microstructure of the light microscope and electron microscope;From blood samples to detect the MDA,superoxide dismutase,glutathione peroxidase,catalase change,and we investigate whether there is correlation between oxidative stress indicators.Results:Serum BUN and Scr detection:E group compared with S group,C groups were statistically difference(P<0.01);S group compared with C group did not make any difference.In FHb detection:no statistical difference between group C with group S;E group compared with group C and S group were statistically significant difference(P<0.01);no statistics difference between group EC and group E(P>0.05).Values of group E were significantly higher in 2hr.In CysC detection:no statistical difference between group C with group S;group E compared with group C and S group were statistically significant difference(P<0.01);value E group was significantly increased in 12hr.In NGAL assay:no significant difference between group C with group S,group E compared with group C and group S were statistically significant difference(P<0.01);value E group was significantly increased in 2hr.In the kidney tissue inflammatory cytokines IL-1?,IL-6,TNF-?,between S group an group C had no statistical difference.ECMO group light microscope and electron microscope acute renal insufficiency of performance,these manifestations are mostly concentrated in the renal tubules and mitochondria partly;During ECMO operation,it presence oxidative stress,and oxidative stress be observed to enhance in the process,renal antioxidant enzyme activity in vivo antioxidant capacity also decreased,it resulted in the occurrence of renal tissue OS.Conclusions:In healthy piglets,VV ECMO treatment have different degrees of acute kidney injury in general kidney function,inflammatory cytokines early indicators of acute kidney injury and kidney tissue expression.In the kidney tissue morphology was also observed in a certain degree of change.Activation of kidney inflammation and oxidative stress is an important mechanism which may cause acute kidney injury associated with injury by VV ECMO.Study ?:Effect of Extracorporeal Membrane Oxygenation and combined with continued renal replacement therapy on the kidney in a healthy piglet modelObjective:we lack the histological changes in the kidneys of basic research during VV-ECMO running.In this study,using low tidal volume ventilation in normal piglets,we research the effect of VV ECMO combined CRRT treatment on the kidney in a healthy piglet model.and we also explore the associated mechanism.Methods:24 healthy piglets in low tidal volume ventilation were randomly divided into four groups:control group,sham group,ECMO group and ECMO combined with CRRT group;They underwent systemic anticoagulation and observed for 24 hours.Conventional hemodynamic changes recorded in general;detected 0h,2h,6h,12h,24h free hemoglobin blood samples(Free Serum Hemoglobin,FHb)level;detected Oh,2h,6h,12h,24h serum urea nitrogen(blood urea nitrogen,BUN)and serum creatinine(Serum creatinine,Scr)and other general changes in renal function.use NGAL and CysC as early detection of acute kidney injury;detect IL-1? IL-6,TNF-?and the expression;Kidney were observed changes in gross morphology and microstructure of the light microscope and electron microscope;to detect the MDA,superoxide dismutase,glutathione peroxidase,catalase change using blood samples and we investigated whether there is correlation between oxidative stress indicators.Results:Serum BUN and Scr detection:E group compared with S group,C groups were statistically difference(P<0.01);statistical difference(P<0.05)between the E group with the EC group;S group compared with C group did not make any difference.In FHb detection:no statistical difference between group C with group S;E group and EC group compared with group C and S group were statistically significant difference(P<0.01);no statistics difference between group EC and group E(P>0.05).Values of group E and EC groups were significantly higher in 2hr,at other time points after 2hr to reach a peak at each time point were gradually increased slowly.In CysC detection:no statistical difference between group C with group S;group E compared with group C and S group were statistically significant difference(P<0.01);there was a significant difference between group EC with group E(P<0.01);value E group was significantly increased in 12hr.In NGAL assay:no significant difference between group C with group S,group E compared with group C and group S were statistically significant difference(P<0.01);there were statistically difference significant between group E and group EC(P<0.01);value E group was significantly increased in 2hr.In the kidney tissue inflammatory cytokines IL-1?,IL-6,TNF-?:There was significant difference(P<0.01)between the E group and the EC group and S group,C group,there were differences(P>0.05)between group EC and group E,between S group an group C had no statistical difference;From light microscope and electron microscope,EC group observation showed improvement in varying degrees of acute renal insufficiency of performance,these manifestations are mostly concentrated in the renal tubules and mitochondria part;we observed presence of oxidative stress in the ECMO during operation,enhance the role of oxidative stress,in its development process,reduce the activity of antioxidant enzymes in vivo antioxidant capacity also,And result in the occurrence of renal tissue OS,but there were improved in EC group.Conclusions:In healthy piglets,VV ECMO combined CRRT treatment can decrease some negative factors of inflammation,oxidative stress by and there were improvement in the kidneys morphological.VV ECMO combined CRRT treatment can reduced damage to the kidneys compared with VV ECMO treatment alone.it is a more optimized treatment.Part ?Effect of Extracorporeal Membrane Oxygenation and combined with continued renal replacement therapy on the kidney in a post-traumatic ARDS piglet modelStudy ?:Establishment of the post-trauma ARDS porcine modelObjective:Currently ARDS model often use oleic acid,aspiration pneumonia,sea water drowning,etc.,but all are unable to meet the needs of serious ARDS model in time or extent due to various reasons.We aimed to establish a post-trauma ARDS porcine model,which was easy to perform and well reproduced.Methods:12 pigs were randomly divided into three groups.In each group,we used weighty fell on the chest of the pig(group A=0.2 kg/(kg weight);group B=0.4 kg/(kg weight);group C=0.6 kg/(kg weight)).Then the pig underwent the systemic ischemia-reperfusion and observed for 24hours.Hemodynamic and ventilation parameters were recorded.We assessed CT score after trauma,and the histopathological changes of lungs.Results:there was no remarkably difference of survival time between groups.The morbidity of Group C was 75%.The animals in Group A all survived.And in Group A,the light changes of oxygenation index,CT score and the pathohistology were ob-served.In Group B,the oxygenation index was between 200 to 300.The CT score indicated that the half lung was contused.And there was mild to severe inflammatory infiltration and exudates in the lung parenchyma.Conclusion:Group B was similar with the changes of pathophysiology in post-trauma ARDS.Study ?:Effect of Extracorporeal Membrane Oxygenation on the kidney in a post-traumatic ARDS piglet modelObjective:large of literature suggests,ECMO contribute to the recovery of patients with ARDS after trauma.In this study,using by post-traumatic ARDS porcine model,we research a comparative study of the sham group(group S),VV ECMO group(group E)effects on renal function.Methods:12 post-traumatic ARDS piglets were randomly divided into two groups:sham group venous catheter;VV ECMO group.They underwent systemic anti coagulation and observed for 24 hours.Conventional hemodynamic changes recorded in general;detected Oh,2h,6h,12h,24h free hemoglobin blood samples(Free Serum Hemoglobin,FHb)level;detected Oh,2h,6h,12h,24h serum urea nitrogen(blood urea nitrogen,BUN)and serum creatinine(Serum creatinine,Scr)and other general changes in renal function;.use of NGAL and CysC and other biomarkers of early detection of acute kidney injury;Kidney were observed changes in gross morphology and microstructure of the light microscope and electron microscope.Results:Serum BUN and Scr detection:E group compared with S group were statistically difference(P<0.01).In FHb detection:E group compared with S group were statistically significant difference(P<0.05);.In CysC detection:E group compared with S group were statistically difference(P<0.05);E group was significantly increased in 12hr.In NGAL assay:E group compared with S group were statistically difference(P<0.05);E group was significantly increased in 2hr.From light microscope and electron microscope,E group compared with S group,E group was observed increased expression of varying degrees of acute renal insufficiency.Conclusions:In post-traumatic ARDS piglets,VV ECMO treatment group compared with S group,renal function have a certain severity in general;we found that early detection biomarkers of acute kidney injury has increased in VV ECMO treatment compared with S group.Free hemoglobin in the detection of VV ECMO treatment compared with S group has increased.Whether it be in an ordinary light microscope or electron microscope,It is heavier in acute exacerbation of renal injury performance when VV ECMO treatment group compared with Shame group.Study ?:Effect of Extracorporeal Membrane Oxygenation and combined with continued renal replacement therapy on the kidney in a post-traumatic ARDS piglet modelObjective:large of literature suggests,ECMO contribute to the recovery of patients with ARDS after trauma.In this study,using by post-traumatic ARDS porcine model,we research a comparative study of the sham group(group S),VV ECMO group(group E)and VV ECMO combined CRRT group(group EC)effects on renal function.Methods:18 post-traumatic ARDS piglets were randomly divided into three groups:sham group venous catheter;VV ECMO group;VV ECMO combined CRRT group.They underwent systemic anticoagulation and observed for 24 hours.Conventional hemodynamic changes recorded in general;detected Oh,2h,6h,12h,24h free hemoglobin blood samples(Free Serum Hemoglobin,FHb)level;detected Oh,2h,6h,12h,24h serum urea nitrogen(blood urea nitrogen,BUN)and serum creatinine(Serum creatinine,Scr)and other general changes in renal function;.Use of NGAL and CysC and other biomarkers of early detection of acute kidney injury;Kidney were observed changes in gross morphology and microstructure of the light microscope and electron microscope.Results:Serum BUN and Scr detection:E group and EC group compared with S group were statistically difference(P<0.01);statistical difference(P<0.05)between the E group with the EC group.In FHb detection:E group and EC group compared with S group were statistically significant difference(P<0.05);no statistical difference between group E with group EC(P>0.05)values.In CysC detection:E group compared with S group and EC group were statistically difference(P<0.05);there was not a statistically difference between the S group with the EC group(P>0.05);E group was significantly increased in 12hr.In NGAL assay:E group compared with S group and EC group were statistically difference(P<0.05);there was not a statistically difference between the S group with the EC group(P>0.05);E group was significantly increased in 2hr.From light microscope and electron microscope,EC group observation showed improvement in varying degrees of acute renal insufficiency of performanceConclusions:In 18 post-traumatic ARDS piglets,VV ECMO combined CRRT treatment compared with VV ECMO alone treatment,we found have improve in general kidney function.The value of free hemoglobin in the detection of VV ECMO alone treatment compared with VV ECMO combined CRRT treatment,it was not significantly difference.it indicated that hemolysis is not the most AKI factor caused by VV ECMO.Whether it be observed on an ordinary light microscope or electron microscope,VV ECMO combined CRRT treatment compared with VV ECMO treatment alone can significantly improve in renal morphological changes.
Keywords/Search Tags:ECMO, CRRT, combination therapy, renal function, biomarkers, oxidative stress
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