The Implantable Pediatric Artificial Lung

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 a PAL’s efficacy 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 20-30kg lambs underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic deadspace 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±2.2mmHg, rPA ligation=28.5±5.2mmHg, p<0.001), and arterial partial pressure of carbon dioxide (PaCO2: baseline=40.4±9.3mmHg, rPA ligation=57.3±12.7mmHg, p=0.026). Of the 7 lambs, 3 were unable to be weaned from mechanical ventilation post-operatively, 3 were successfully weaned but suffered cardiorespiratory failure within 4 days, and 1 survived all 4 days. All 4 animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA=28.6±2.2mmHg) and remained tachypneic (respiratory rate=63±21min−1). Three of the 4 recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric end-stage lung failure and may be suitable for testing and implanting a PAL.

Development of a Model of Pediatric Lung Failure Pathophysiology

“…Our previous model was effective in meeting our physiologic goals, but had an unacceptably high rate of immediate postoperative mortality thought to be due to the challenge of recovering from anesthesia in the face of acute RV dysfunction. 7 …”

“…Baseline instrumentation was identical to our previous published methods. 7 Briefly, healthy lambs (25–40 Kg) were anesthetized, intubated, and mechanically ventilated at a frequency of 12 breaths per minute and tidal volume of 15 mL/Kg. Each animal had arterial, venous, and oximetric pulmonary arterial catheters placed (which were left in place postoperatively for data collection), and baseline arterial and venous blood gases and hemodynamics were recorded.…”

“…7 For the new set of animals, the same left thoracotomy was performed, and the left and right branches of the main pulmonary artery dissected. The occlusion device, which consisted of a flexible Rummel tourniquet device (rPA-RT) was placed around the rPA.…”

“…Animals received antibiotics and PRN pain control according to our established animal protocols. 7 Supplemental oxygen, when needed, was administered via nasal cannula and titrated to an arterial saturation of >92%. Thoracostomy tubes were removed according to standard clinical criteria.…”

“…7 In this study, we introduced a major modification of our methods to induce rPA occlusion after full recovery from the thoracotomy and anesthesia using a Rummel tourniquet (rPA-RT). This new method allows for successful recovery of the animals, followed by slow and reversible titration of the rPA occlusion until full occlusion is achieved.…”