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A Model of Pediatric End-Stage Lung Failure in Small Lambs <20 kg

Carr, Benjamin D.*,†; Poling, Clinton J.*; Hala, Pavel*,‡,§,¶; Caceres Quinones, Matias*,‖,#; Prater, Aaron R.*; McLeod, Jennifer S.*,†; Bartlett, Robert H.*; Rojas-Pena, Alvaro*,#; Hirschl, Ronald B.*,†

doi: 10.1097/MAT.0000000000001017
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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.

From the *Extracorporeal Life Support Laboratory, Department of Surgery

Department of Pediatric Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Michigan

Department of Cardiology, Homolka Hospital

§Department of Physiology, Charles University, Prague, Czech Republic

Department of Pediatric Anesthesia, Hospital Luis Calvo Mackenna, University of Chile

Department of Anesthesia, Clínica Las Condes, Santiago, Chile

#Department of Surgery, Section of Transplantation, Michigan Medicine, University of Michigan, Ann Arbor, Michigan.

Submitted for consideration October 2018; accepted for publication in revised form April 2019.

Disclosure: The authors have no conflicts of interest to report.

Tis work was supported by NIH R01 HD015434-35, and in part by the University of Michigan Undergraduate Research Opportunity Program.

Corresponence: Alvaro Rojas-Pena, Extracorporeal Life Support Laboratory, B560, MSRB II, SPC5686 1150 W, Medical Center Dr., Ann Arbor, MI 48109. Email: alvaror@med.umich.edu.

Copyright © 2019 by the American Society for Artificial Internal Organs