Caminita Frank, van der Merwe Marie, Hance Brittany, Krishnan Ramesh, Miller Sarah, Buddington Karyl, Buddington Randal K
Draeger Medical, Telford, Pennsylvania;
Department of Health and Sport Science, University of Memphis, Memphis, Tennessee;
Am J Physiol Lung Cell Mol Physiol. 2015 Jan 15;308(2):L118-29. doi: 10.1152/ajplung.00173.2014. Epub 2014 Nov 14.
Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia remain the leading causes of preterm infant morbidity, mortality, and lifelong disability. Research to improve outcomes requires translational large animal models for RDS. Preterm pigs delivered by caesarian section at gestation days (GD) 98, 100, 102, and 104 were provided 24 h of neonatal intensive care, monitoring (pulse oximetry, blood gases, serum biomarkers, radiography), and nutritional support, with or without intubation and mechanical ventilation (MV; pressure control ventilation with volume guarantee). Spontaneous development of RDS and mortality without MV are inversely related with GD at delivery and correspond with inadequacy of tidal volume and gas exchange. GD 98 and 100 pigs have consolidated lungs, immature alveolar architecture, and minimal surfactant protein-B expression, and MV is essential at GD 98. Although GD 102 pigs had some alveoli lined by pneumocytes and surfactant was released in response to MV, blood gases and radiography revealed limited recruitment 1-2 h after delivery, and mortality at 24 h was 66% (35/53) with supplemental oxygen provided by a mask and 69% (9/13) with bubble continuous positive airway pressure (8-9 cmH2O). The lungs at GD 104 had higher densities of thin-walled alveoli that secreted surfactant, and MV was not essential. Between GD 98 and 102, preterm pigs have ventilation inadequacies and risks of RDS that mimic those of preterm infants born during the saccular phase of lung development, are compatible with standards of neonatal intensive care, and are alternative to fetal nonhuman primates and lambs.
呼吸窘迫综合征（RDS）和支气管肺发育不良仍然是早产婴儿发病、死亡和终身残疾的主要原因。改善治疗效果的研究需要用于RDS的转化性大型动物模型。在妊娠第98、100、102和104天通过剖宫产分娩的早产猪接受了24小时的新生儿重症监护、监测（脉搏血氧饱和度、血气、血清生物标志物、放射照相）和营养支持，有无插管和机械通气（MV；压力控制通气并保证潮气量）。在没有MV的情况下，RDS的自然发展和死亡率与分娩时的妊娠天数呈负相关，并且与潮气量和气体交换不足相对应。妊娠第98天和第100天的猪肺部实变，肺泡结构不成熟，表面活性蛋白-B表达极少，在妊娠第98天MV是必不可少的。尽管妊娠第102天的猪有一些肺泡被肺细胞覆盖，并且表面活性剂在MV作用下释放，但分娩后1-2小时的血气和放射照相显示肺复张有限，24小时死亡率在通过面罩提供补充氧气时为66%（35/53），在采用气泡持续气道正压通气（8-9 cmH2O）时为69%（9/13）。妊娠第104天的猪肺部薄壁肺泡密度更高，可分泌表面活性剂，MV并非必不可少。在妊娠第98天至第102天之间，早产猪存在通气不足和RDS风险，这些风险与在肺发育囊泡期出生的早产婴儿相似，符合新生儿重症监护标准，并且可替代胎儿非人灵长类动物和羔羊。
