From the Extracorporeal Life Support Laboratory, Department of Surgery.
Department of Pediatric Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.
ASAIO J. 2020 May;66(5):572-579. doi: 10.1097/MAT.0000000000001017.
One in five children with end-stage lung failure (ESLF) die while awaiting lung transplant. No suitable animal model of ESLF exists for the development of artificial lung devices for bridging to transplant. Small lambs weighing 15.7 ± 3.1 kg (n = 5) underwent ligation of the left anterior pulmonary artery (PA) branch, and gradual occlusion of the right main PA over 48 hours. All animals remained hemodynamically stable. Over seven days of disease model conditions, they developed pulmonary hypertension (mean PA pressure 20 ± 5 vs. 33 ± 4 mm Hg), decreased perfusion (SvO2 66 ± 3 vs. 55 ± 8%) with supplemental oxygen requirement, and severe tachypneic response (45 ± 9 vs. 82 ± 23 breaths/min) (all p < 0.05). Severe right heart dysfunction developed (tricuspid annular plane systolic excursion 13 ± 3 vs. 7 ± 2 mm, fractional area change 36 ± 6 vs. 22 ± 10 mm, ejection fraction 51 ± 9 vs. 27 ± 17%, all p < 0.05) with severe tricuspid regurgitation and balloon-shaped dilation of the right ventricle. This model of pediatric ESLF reliably produces pulmonary hypertension, right heart strain, and impaired gas exchange, and will be used to develop a pediatric artificial lung.
五分之一患有终末期肺衰竭(ESLF)的儿童在等待肺移植时死亡。目前尚无合适的 ESLF 动物模型来开发用于移植桥接的人工肺设备。5 只体重为 15.7 ± 3.1 kg 的小羔羊接受了左前肺动脉(PA)分支结扎术,并在 48 小时内逐渐阻塞右主 PA。所有动物均保持血流动力学稳定。在七天的疾病模型条件下,它们发展为肺动脉高压(平均 PA 压 20 ± 5 与 33 ± 4 mmHg),灌注减少(SvO2 66 ± 3 与 55 ± 8%,需要补充氧气),以及严重的呼吸急促反应(45 ± 9 与 82 ± 23 次/分钟)(均 p < 0.05)。严重的右心功能障碍发展(三尖瓣环平面收缩期位移 13 ± 3 与 7 ± 2 mm,分数面积变化 36 ± 6 与 22 ± 10 mm,射血分数 51 ± 9 与 27 ± 17%,均 p < 0.05),伴有严重的三尖瓣反流和右心室球囊样扩张。这种儿科 ESLF 模型可靠地产生肺动脉高压、右心劳损和气体交换受损,并将用于开发儿科人工肺。