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The Implantable Pediatric Artificial Lung: Interim Report on the Development of an End-Stage Lung Failure Model
Fares Alghanem1, Ryan P Davis, Benjamin S Bryner
1From the *Department of Surgery, University of Michigan, Extracorporeal Life Support Laboratory, Ann Arbor, Michigan; †Section of General Surgery, Department of Surgery, Columbia University, New York, New York; ‡Section of Transplant Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan; and §Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Insights
Right pulmonary artery ligation in lambs effectively models pediatric end-stage lung failure. This animal model is crucial for testing implantable pediatric artificial lungs (PAL) before clinical trials.
Area of Science:
- Biomedical Engineering
- Pediatric Critical Care
- Cardiovascular Surgery
Background:
- Pediatric end-stage lung failure (ESLF) necessitates innovative treatments like implantable pediatric artificial lungs (PAL).
- Evaluating PAL efficacy requires a suitable animal model for pediatric ESLF.
Purpose of the Study:
- To assess the feasibility of right pulmonary artery (rPA) ligation as an animal model for pediatric ESLF.
- To determine if this model replicates the physiological conditions of pediatric lung failure.
Main Methods:
- Seven lambs (20-30 kg) underwent rPA ligation.
- Physiological parameters including dead space fraction (Vd/Vt), mean pulmonary arterial pressure (mPPA), and arterial partial pressure of carbon dioxide were monitored.
- Animal outcomes were observed for up to 4 days post-procedure.
Main Results:
- rPA ligation significantly increased Vd/Vt, mPPA, and arterial partial pressure of carbon dioxide.
- Postoperatively, 3 lambs required mechanical ventilation, 3 experienced cardiorespiratory failure, and 1 survived 4 days.
- Survivors exhibited persistent pulmonary hypertension and tachypnea, with 3 requiring supplemental oxygen.
Conclusions:
- rPA ligation effectively induces physiological derangements consistent with pediatric ESLF.
- This model shows promise for evaluating implantable pediatric artificial lungs (PAL) in a preclinical setting.
Abstract:
An implantable pediatric artificial lung (PAL) may serve as a bridge to lung transplantation for children with end-stage lung failure (ESLF); however, an animal model of pediatric lung failure is needed to evaluate the efficacy of PAL before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven lambs weighing 20-30 kg underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic dead space fraction (Vd/Vt; baseline = 48.6 ± 5.7%, rPA ligation = 60.1 ± 5.2%, p = 0.012), mean pulmonary arterial pressure (mPPA; baseline = 17.4 ± 2.2 mm Hg, rPA ligation = 28.5 ± 5.2 mm Hg, p < 0.001), and arterial partial pressure of carbon dioxide (baseline = 40.4 ± 9.3 mm Hg, rPA ligation = 57.3 ± 12.7 mm Hg, p = 0.026). Of the seven lambs, three were unable to be weaned from mechanical ventilation postoperatively, three were successfully weaned but suffered cardiorespiratory failure within 4 days, and one survived all 4 days. All four animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA = 28.6 ± 2.2 mm Hg) and remained tachypneic (respiratory rate = 63 ± 21 min). Three of the four recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric ESLF and may be suitable for testing and implanting a PAL.
