A preterm pig model of lung immaturity and spontaneous infant respiratory distress syndrome.
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.
Draeger Medical, Telford, Pennsylvania;
Frank
F
Caminita
Department of Health and Sport Science, University of Memphis, Memphis, Tennessee;
Marie
M
van der Merwe
Department of Health and Sport Science, University of Memphis, Memphis, Tennessee;
Brittany
B
Hance
Division of Neonatology, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee;
Ramesh
R
Krishnan
Loewenburg School of Nursing, University of Memphis, Memphis, Tennessee; and.
Sarah
S
Miller
Director of Animal Care, University of Memphis, Memphis, Tennessee rbddngtn@memphis.edu.
Karyl
K
Buddington
Department of Health and Sport Science, University of Memphis, Memphis, Tennessee;
Randal K
RK
Buddington
D000818:Animals; D015415:Biomarkers; D001997:Bronchopulmonary Dysplasia / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015931:Intensive Care, Neonatal; D008168:Lung / Q000196:embryology*; D008297:Male; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000000981:diagnostic imaging / Q000196:embryology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis; D011859:Radiography; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000473:pathology*; D013552:Swine
D015415:Biomarkers; D037701:Pulmonary Surfactant-Associated Protein B; D051523:Fibroblast Growth Factor 7
animal model; development; fetus; pulmonary