High inspired oxygen contributes to development of bronchopulmonary dysplasia [BPD]. In vitro studies have demonstrated increased contractility of tracheal segments to electrical field stimulation in hyperoxia-exposed infant rats. We sought to develop an in vivo model for evaluating the effects of prolonged hyperoxic exposure on contractile responses of lower airways to endogenously released acetylcholine. Nine day old suckling rat pups were exposed to either room air [n=9] or hyperoxia[>95% O2, n=9] for 5-6 days. Under metofane anesthesia the animals were decerebrated, tracheotomized, paralyzed, and mechanically ventilated in a body plethysmograph for recording airflow and tracheal pressure. Lung resistance was calculated by ANADAT 5.2 software using the least squares technique. Distal ends of both severed vagi were placed on bipolar stimulating electrodes and β-sympathetic blockade achieved with propanolol, 1 μg/g IV. Repeated bilateral vagal stimulation was applied for 5 sec [1 ms pulse duration, 50 mA current] every 3 min with increasing frequencies. Hyperoxia did not alter baseline lung resistance [p=.066] and compliance [p=.07] significantly. The response of pulmonary resistance to vagal stimulation was enhanced in hyperoxic animals vs controls [ANOVA, p=.023] and abolished by atropine [1 μg/g] IV in both groups. We conclude that prolonged hyperoxic exposure in maturing rats results in bronchopulmonary hyperresponsiveness to endogenously released acetylcholine. This model will allow characterization of neural mechanisms underlying airway hyperreactivity during development. Figure
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Support: NIH 56470; 50527
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Iben, S., Dreshaj, I., Haxhiu, M. et al. Hyperoxic Exposure Enhances Contractile Responses of Lower Airways to Endogenously Released Acetylcholine in Maturing Rats ♦ 1675. Pediatr Res 43 (Suppl 4), 286 (1998). https://doi.org/10.1203/00006450-199804001-01697
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DOI: https://doi.org/10.1203/00006450-199804001-01697