The Study Of The Relevance Between The Perioperative Variation Of The Treg/Th17 Axis In Adults Cardiac Valvular Surgery With Extracorporeal Circulation And The Post-Operative Lung Dysfunction

Objective①The aim of this study is to observe the perioperative variation of the Treg/Th17 axis in adult patients who developed PPD after cardiac valvular surgery with extracorporeal circulation,and to identify whether the ratio of Treg/Thl7 could predict the severity of PPD;②To establish a extracorporeal circulation rat model with the advantages of stablilazation and repeatability.Method①This prospective,observational study enrolled 81 patients from Zhongshan Hospital who received cardiac valvular surgery with extracorporeal circulation.The baseline characteristics of patients such as age,gender,LVEF,NYHA,pre-operative HCT,minimal HCT,extracorporeal circulation time,clamping time,CSICU-stay time,incubation time,Pa02/Fi02 were collected.According to the 2012 Berlin ARDS definition,Patients were divided into 3 groups:no PPD,mild PPD,moderate PPD.APACHE II.EUROSCORE II and SIRS score were calculated after surgery.Blood samples were take respectively before anesthesiation(T1),20min after protamine administration(T2),2h after the termination of extracorporeal circulation(T3),24h after the surgery(T4).Circulating Treg and Th17 cell frequencies were analyzed by flow cytometry,and expressions of Treg-and Th 17-related cytokins were dertermined by cytometric bead array(CBA);②15 adult male Sprague-Dawley rats received anesthesia induction with chloral hydrate by intraperitoneal administTreg/Th17n,maintain mechanicl ventilation by transoral treacheal intubation using a 14G catheter.During the surgical prepaTreg/Thl7n period,a homemade multi lateral orifice 16G catheter was cannulated in the right jugular vein for venous drainage,a 20G catheter was cannulated in the right carotid artery for arterial inflow,and a 24G catheter was cannulater in the left femoral artery for monitoring the blood pressure.The blood was oxygenated in the small animal special purposed oxygenator.The ECC was lasted for 60 minutes.Hemodynamic parameters and blood analysis were monitored before ECC,during ECC and after ECC.Result①Varation of Treg/Th17 axis and its related cytokins is significant durting the perioperative period,especially in moderate PPD patients.Compared to patients with no PPD or mild PPD,the Treg cell frequences,Treg/Th17 ratio and concentration of Treg-related cytokine IL-10 at T2 in moderate PPD patients were all higher(P=0.0214,P=0.0302,P<0.001),while Th17 cell frequences and concentration of Th 17-related cytokine IL-17A at T4 were lower(P<0.01).The Treg frequencies and Treg/Th17 ratio at T2 were positively correlated with the PaO2/FiO2 between 100 to 200(r=0.6606,P=0.0438;r=0.4833,P=0.0422).The area under the curve(AUC)of the Treg frequencies and Treg/Th17 ratio at T2 were 0.7086(95%CI 0.527～0.89),0.693(95%CI 0.46～0.928),higher than AUC of the APACHE II 0.648(95%CI 0.487～0.798),EUROSCORE II 0.632(95%CI 0.464～0.799)and SIRS score 0.624(95%CI 0.441～0.807);②the first 3 of 15 rats died during the progress of establishement of ECC model,the rest 12 rats survived more than 1 day,whose hemodynamic parameters and blood analysis in different time points were in accord with the normal standard.Vital sighs of the 12 rats were stable after the termination of ECC.Conclusion①Our data suggests that a Treg/Th17 imbalance due to a Treg shift,representing a anti-inflammatory tendency,participates in the development of PPD.Treg cell contributes to the anti-inflammatory response and protection of the pulmonary function.Treg frequencies and Treg/Th17 ratio of patient developing moerate PPD at the end of extracorporeal circulation is positively correlated with the oxygenation index 24 hours after surgery.We speculate the Treg frequencies and Treg/Th17 ratio of patient developing moderate PPD at the end of extracorporeal circulation may be a additional predictor for patients suffered pulmonary dysfunction undergoing cardiac valvular surgery with extra corporeal circulation;②The exsanguine priming ECC rats model was successfully established.The reliable model could be used for further resarch,study of the ECC-related organ injury and pretection during perioperative period.