房间隔造口术联合体外膜肺治疗急性呼吸窘迫综合征合并左心功能不全的大动物实验研究

A large animal experimental study on the treatment of acute respiratory distress syndrome with left ventricular dysfunction by atrial septal defect combined with extracorporeal membrane oxygenation

目的:探索房间隔造口术(ASD)联合体外膜肺(ECMO)治疗ARDS合并左心功能不全的效果,以便为治疗新型冠状病毒肺炎(COVID-19)重症合并左心衰竭患者寻找一条有效的新方法。方法:应用静脉泵入脂多糖(LPS)方法制作成年绵羊的急性呼吸窘迫综合征(ARDS)合并左心大动物模型5只,在全麻体外循环下完成房间隔缺损(1~2 cm),在应用体外循环机模拟静脉-动脉体外膜肺(VAECMO)工作状态下,对比观察在ASD闭合和开放状态下动物的外周血氧合情况和体循环状态,以及心脏功能情况,评价ASD分流对改善心肺功能的意义。结果:在闭合ASD的情况下,房水平分流消失,仅应用VA-ECMO辅助下可见动物吸入100%氧的情况下心率(HR):(108±17)次/min,平均血压(MAP):(49.3±13.5)mmH g,肺动脉压力(PAP):(28.9±12.7)mmH g,肺血管阻力指数(PVRI):(45.2±9.2)N·S·M^-2·L^-1,外周动脉PaO2为(141.2±21.4)mmH g,SaO2:(96.1±1.3)%,氧合指数(PaO2/FiO2)为(353.0±53.5),心脏饱胀,运动幅度较小,显得无力;在其他实验条件不变的情况下,仅打开ASD后房水平出现左向右分流,MAP:(68.2±16.1)mmH g,PAP:(18.1±7.8)mmH g,PVRI:(33.4±7.2)N·S·M^-2·L^-1,外周动脉PaO2明显上升至(169.3±18.9)mmH g,SaO2:(98.2±1.1)%,PaO2/FiO2为(423.3±47.3),心率(98±18)次/min,心脏运动幅度明显加大,心脏跳动显得轻松,体循环状态明显好转。与ASD关闭时比较,在ASD开放后MAP,PaO2,SaO2,PaO2/FiO2明显上升;PAP,PVRI明显下降。二者间差异有统计学意义(P<0.01)。结论:房间隔造口术联合VA-ECMO是治疗ARDS合并左心功能不全(LVF)者的一种有效方法,对于COVID-19引起的重症ARDS合并LVF的患者治疗有一定的借鉴意义,需要临床应用进一步验证。

Objective:To explore the effect of atrial septal defect(ASD)combined with extracorporeal membrane oxygenation(ECMO)in the treatment of acute respiratory distress syndrome(ARDS)complicated with left ventricular dysfunction.Methods:5 animal models of ARDS with left ventricle dyfunction in sheep were established by intravenous injection of lipopolysaccharide(LPS),after 1-2 cm ASD was completed under general anesthesia and VA-ECMO was simulated by extracorporeal circulation machine,the oxygenation of pe-ripheral blood,systemic circulation and cardiac function were observed under closed and opened ASD,and the significance of ASD shunt in improving cardiopulmonary function was evaluated.Results:With ASD closed,no atrial shunts were seen.Heart rate(HR)was(108±17)beats/min,mean blood pressure(MAP)was(49.3±13.5)mmH g,pulmonary artery pressure(PAP)was(28.9±12.7)mmH g,pulmonary vascular resistance index(PVRI)was(45.2±9.2)N·S·m-2·L-1,the peripheral artery PaO2 was(141.2±21.4)mmHg,SaO2:(96.1±1.3)%,the oxygenation index(PaO2/FiO2)was(353.0±53.5),the heart was full,the range of motion was small,and the left-to-right shunts occurred only after ASD was opened,MAP:(68.2±16.1)mmH g;PAP:(18.1±7.8)mmH g;PVRI:(33.4±7.2)N·S·m-2·L-1;peripheral artery PaO2 increased significantly to(169.3±18.9)mmH g;SaO2:(98.2±1.1)%;PaO2/FiO2 was(423.3±47.3);HR was(98±18)beats/min,the range of cardiac motion was obviously increased,the heart beat was relaxed,and the systemic circulation was obviously improved.Compared with ASD closure,MAP,PaO2,SaO2,PaO2/FiO2 increased significantly and PAP,PVRI decreased significantly after ASD opening.There was significant difference between them(P<0.01).Conclusions:Atrial septostomy combined with VA-ECMO is an effective method to treat patients with ARDS complicated with left ventricular dysfunction.It has certain reference significance for the treatment of severe ARDS caused by COVID-19 complicated with LVD patients,and needs to be further validated by clinical application.