Establishment Of Large Animal Extracorporeal Membrane Oxygenation Model And Analysis Of Risk Factors For Renal Injury During Extracorporeal Membrane Oxygenatio

Background:Large animal models are developed to.help understand physiology and explore clinical translational significance in the continuous development of veno-arterial extracorporeal membrane oxygenation(VA-ECMO)technology.The purpose of this study was to investigate the establishment methods and management strategies in an ovine model of VA-ECMO.Methods:Seven sheep underwent VA-ECMO support for 7 days by cannulation via the right jugular vein and artery.The animals were transferred into the monitoring cages after surgery and were kept awake after anesthesia recovery.The hydraulic parameters of ECMO,basic hemodynamics,mental state,and fed state of sheep were observed in real time.Blood gas analysis and activated clotting time(ACT)were tested every 6 h,while the complete blood count,blood chemistry,and coagulation tests were monitored every day.Sheep were euthanized after 7 days.Necropsy was performed and the main organs were removed for histopathological evaluation.Results:Five sheep survived and successfully weaned from ECMO.Two sheep died within 24-48 h of ECMO support.One animal died of fungal pneumonia caused by reflux aspiration,and the other died of hemorrhagic shock caused by bleeding at the left jugular artery cannulation site used for hemodynamic monitoring.During the experiment,the hemodynamics of the five sheep were stable.The animals stayed awake and freely ate hay and feed pellets and drank water.With no need for additional nutrition support or transfusion,the hemoglobin concentration and platelet count were in the normal reference range.The ECMO flow remained stable and the oxygenation performance of the oxygenator was satisfactory.No major adverse pathological injury occurred.Conclusions:The perioperative management strategies and animal care are the key points of the VA-ECMO model in conscious sheep.This model could be a platform for further research of disease animal models,pathophysiology exploration,and new equipment verification.Background:In recent years,it has become a promising approach to respiratory support for awake,non-intubated,spontaneously breathing patients with respiratory failure,referred to as awake veno-venous extracorporeal membrane oxygenation(VV-ECMO).The purpose of our study was to explore the feasibility and stability of the establishment method of awake VV-ECMO model in sheep.Methods:Nine sheep treated with awake VV-ECMO through a single-site dual lumen cannula for 7 days.They stayed awake and could eat and move in the monitoring cage during awake VV-ECMO support.ECMO running parameters,hemodynamic and hematologic parameters were monitored every day.After 7 days,ECMO was removed,sheep were euthanized and necropsy was performed to visualize the cannula position in vivo and to examine cannulation related injury.Main organs were harvested for pathological evaluation.Results:All nine sheep survived and successfully weaned from ECMO.With no need of artificial nutrition or blood transfusion,the vital signs of the sheep were stable,and no serious bleeding and coagulation events occurred.Hemodynamic and hematological indexes were in normal range.ECMO flow remained stable,and oxygenation performance of oxygenator was satisfied.There was no major adverse pathological injury occurred.Conclusions:The awake VV-ECMO model through a single-site dual lumen cannula in sheep is feasible and stable.As a basic research,it can provide a basis for further research especially in the establishment of a disease large animal model and pathophysiology exploration.Background:Based on the establishment of extracorporeal membrane oxygenation(ECMO)model in large animals(sheep),we observed the changes of renal function related biomarkers during ECMO support and after weaning.At the same time,we compared the effect of different support modalities on renal function during veno-arterial(V-A)and veno-venous(V-V)ECMO support.Methods:Ten healthy adult sheep were randomly divided into two groups,5 supported by V-A modality and the other 5 supported by V-V modality.The animals underwent awake ECMO support for seven days(168 h)by cannulation via the right jugular vein and artery(V-A)or right jugular vein(V-V,dual lumen cannula).The basic hemodynamic parameters of the sheep and ECMO performance were monitored every day.In addition to monitor the creatinine levels,the levels of kidney injury molecule 1(KIM1)in plasma(before operation,6 h after operation and every 24 h after operation)were measured by enzyme-linked immunosorbent assay(ELISA).At the end of the experiment,gross anatomy and histopathological analysis of kidney were performed.Results:All 10 sheep survived and successfully weaned from ECMO.During the experiment,the basic hemodynamic parameters of the two groups were stable,and the pulse pressure in VA-ECMO group was significantly lower than that in VV-ECMO group.The ECMO flow was stable,and the free hemoglobin was at a low level.Compared with the baseline,the creatinine levels during VV and VA-ECMO support were decreased and remained stable.Although the KIM1 fluctuated during VV-ECMO support,it was lower than the baseline.Compared with the preoperative baseline,the levels of KIM1 during VA-ECMO support were maintained stable.There was no significant difference in creatinine and KIM1 between VV and VA-ECMO groups.The gross specimen and pathological anatomy of kidney in experimental sheep were generally normal.Conclusions:In the model of awake ECMO in healthy sheep,when ECMO run for 7 days,the renal function of the sheep supported by both modalities was in the normal range.When the ECMO circuit did not cause obvious blood damage and the inflammatory response was at a low level,compared with the VV-ECMO group,the hemodynamic changes during VA-ECMO support did not have a significant impact on the renal function,or the impact could be compensated.Background:Studies have shown that 2-6%of patients undergoing cardiac surgery developed cardiogenic shock,and about 1%of patients with cardiogenic shock after cardiac surgery needed veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support.Acute kidney injury(AKI)is one of the most common complications in patients supported by extracorporeal membrane oxygenation(ECMO).The occurrence of severe AKI will significantly affect the prognosis of patients.The purpose of this study was to describe the incidence of AKI and severe AKI in patients with postcardiotomy cardiogenic shock supported by VA-ECMO,and to determine the risk factors of severe AKI.Methods:This study was a single center retrospective study.The patients with postcardiotomy cardiogenic shock supported by VA-ECMO from January 1,2009 to December 31,2020 were reviewed.Patients were divided into patients with stage 3 AKI group and patients without stage 3 AKI group according to the guidelines for Kidney Disease:Improving Global Outcomes(KDIGO).Univariable and multivariable logistic regression analysis were used to explore the independent risk factors of severe AKI in patients with postcardiotomy cardiogenic shock supported by VA-ECMO.Results:A total of 136 patients were included in this study.The overall incidence of AKI in patients with postcardiotomy cardiogenic shock supported by VA-ECMO was 83.8%,of which the incidence of severe AKI was 58.8%.The occurrence of severe AKI significantly increased the total hospital stay(p=0.022),ICU time(p=0.001)and mechanical ventilation time(p<0.001).Multivariale logistic regression analysis showed that ECMO initiation time was an independent risk factor for severe AKI in patients with postcardiotomy cardiogenic shock supported by VA-ECMO(OR 0.294;95%CI 0.104-0.833,p=0.021).Compared with postoperative VA-ECMO implantation,intraoperative VA-ECMO implantation was a protective factor for the occurrence of severe AKI.Conclusions:Severe AKI is particularly frequent in patients with postcardiotomy cardiogenic shock supported by VA-ECMO.Early implantation of VA-ECMO may help prevent severe AKI.Extracorporeal membrane oxygenation(ECMO)is an adjuvant therapy for patients with heart or respiratory failure to obtain short-term extracorporeal life support(ECLS)through mechanical circulatory assist device.Animal models are the basis of ECLS research.Based on animal models,we can carry out physiological research and molecular mechanism research,and provide important reference for clinical trials.The purpose of this paper was to systematically review the characteristics and establishment methods of large animal models with ECMO,and to optimize the relevant strategies for model establishment in future research design.