Lung volume recruitment in a preterm pig model of lung immaturity

Esmond L Arrindell, Ramesh Krishnan, Marie van der Merwe, Frank Caminita, Scott C Howard, Jie Zhang, Randal K Buddington

A translational preterm pig model analogous to infants born at 28 weeks of gestation revealed that continuous positive airway pressure results in limited lung recruitment but does not prevent respiratory distress syndrome (RDS); whereas, assist-control + volume guarantee (AC+VG) ventilation improves recruitment, but can cause injury, highlighting the need for improved ventilation strategies. We determined whether airway pressure release ventilation (APRV) can be used to recruit the immature lungs of preterm pigs without injury. Spontaneously breathing pigs delivered at 89% of term (model for 28 week infants) were randomized to 24 hours of APRV (n=9) versus AC+VG with a tidal volume of 5ml/kg (n=10). Control pigs (n=36) were provided with supplemental oxygen by an open mask. Nutrition and fluid support was provided throughout the 24-hour period. All pigs supported with APRV and AC+VG survived 24 hours, compared to 62% of control pigs. APRV resulted in improved lung volume recruitment compared with AC+VG based on radiographs, lower PCO2 levels (44±2.9 vs 53±2.7 mm Hg, p=0.009) and lower FiO2 requirements (36±6 vs 44±11 %, p<0.001), and higher oxygenation index (5.1±1.5 vs 2.9±1.1, p=0.001). There were no differences between APRV and AC+VG pigs for heart rate, wet/dry lung mass, pro-inflammatory cytokines, or histopathologic markers of lung injury. Lung protective ventilation with APRV improved recruitment of alveoli of preterm lungs, enhanced development and maintenance of functional residual capacity without injury, and improved clinical outcomes relative to AC+VG. Long-term consequences of lung volume recruitment using APRV should be evaluated.