The Implantable Pediatric Artificial Lung: Interim Report on the Development of an End-Stage Lung Failure Model

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.

Figure 1. Modified Ventilation Circuit For Collection And Measurement Of Mixed Expired Gas

Modified ventilation circuit for collection and measurement of mixed expired gas. The intermittent positive pressure breathing valve separates inspiratory and expiratory gases. The mixing chamber creates turbulent airflow. The distal capnograph measures partial pressure of mixed expired carbon dioxide (PmCO₂).

Figure 2

Intraoperative And Postoperative Mean Pulmonary Artery Pressure

Figure 3. Kaplan-Meier Survival Curve

All deaths were due to severe respiratory failure.

Figure 4. Dead Space In An Animal Model Of Chronic Lung Disease

A: Anatomic dead space arising from non-exchange airways is constant. B: Alveolar dead space depends on perfusion of the lung. When the right pulmonary is ligated, alveolar dead space in that lung increases, but alveolar dead space in the left lung drops to compensate. (Note that this figure has been redrawn to correspond to human lung West zones; in quadruped animal models the lung zones are rotated 90°).