LAUSR

BACKGROUND Investigation of pathophysiology of lung impairment and protection in very preterm neonates at birth require adequate experimental models. This study aimed to elucidate efficacy and mechanism of perinatal pharmacotherapeutic action in postnatal survival of very preterm rabbits. METHODS Pregnant New Zealand White rabbits on 25-day gestation (term 31 days) were given dexamethasone (D), or sham injection as control (C), and cesarean delivered 24 hours later on day 26. Newborns were anesthetized, intratracheally intubated, randomly received either saline or porcine surfactant (S), allocated to four groups (C, S, D, DS), and ventilated with low tidal volume. Under the identical protocol, another four groups were added with nitric oxide (N) inhalation (CN, SN, DN, DSN). Survival length, lung mechanics, histopathology and pathobiology of lung tissue were measured for benefits and injury patterns. RESULTS DSN had the longest median survival time (ST50, 10.3 h) while C had the shortest (3.5 h), with remaining groups in-between. The survival was mainly benefited by S, when additive effects with D and/or N were discernible, by improved lung mechanics and alveolar aeration, ameliorated lung injury severity and pneumothorax, and augmented lung phospholipid pools, with DSN being the most optimal. Variable mRNA expression profiles of alveolar epithelia-associated cytokines and inflammatory mediators further characterized injury and response patterns as phenotyping conditioned in pharmacotherapeutic actions. CONCLUSION The combined regimens of perinatal medications achieved remarkable survival in very preterm rabbits with lung protective ventilation strategy, offering a unique model in investigation of very preterm birth-associated respiratory physiology and morbidities.