Antenatal Endotoxin Impairs Lung Mechanics and Increases Sensitivity to Ventilator-Induced Lung Injury in Newborn Rat Pups.

Autor: Mandell EW; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Neonatology, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Mattson C; Department of Bioengineering, College of Engineering, Design, and Computing, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, United States., Seedorf G; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Ryan S; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Neonatology, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Gonzalez T; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Neonatology, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Wallbank A; Department of Bioengineering, College of Engineering, Design, and Computing, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, United States., Bye EM; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Neonatology, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Abman SH; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States., Smith BJ; Department of Pediatrics, Pediatric Heart Lung Center, School of Medicine, University of Colorado, Aurora, CO, United States.; Department of Bioengineering, College of Engineering, Design, and Computing, University of Colorado Denver | Anschutz Medical Campus, Aurora, CO, United States.; Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States.
Jazyk: angličtina
Zdroj: Frontiers in physiology [Front Physiol] 2021 Jan 13; Vol. 11, pp. 614283. Date of Electronic Publication: 2021 Jan 13 (Print Publication: 2020).
DOI: 10.3389/fphys.2020.614283
Abstrakt: Perinatal inflammation due to chorioamnionitis and ventilator-induced lung injury (VILI) at birth is independent risk factors for the development of bronchopulmonary dysplasia (BPD). We have previously shown that antenatal endotoxin (ETX) causes abnormal lung structure and function in 2-week-old rats, but whether ETX impairs lung mechanics at birth and increases risk for VILI is unknown. Fetal rats were exposed to 10 μg endotoxin or saline via intra-amniotic injection. At birth (D0) or 7 days (D7), rats received 90 min of lung protective ventilation [PROTECT group; tidal volume (Vt) = 6 ml/kg with positive end expiratory pressure (PEEP) = 2 cmH 2 O]; P20 ventilation [plateau pressure (Pplat) = 20 cmH 2 O, PEEP = 0]; or P24 ventilation (Pplat = 24 cmH 2 O, PEEP = 0, only applied to D7). Prior to prolonged ventilation at D0, endotoxin-exposed rats had decreased compliance and inspiratory capacity (IC) compared to controls. At D7, endotoxin was associated with reduced compliance. High-pressure ventilation (P20 and P24) tended to increase IC and compliance in all saline-treated groups. Ventilation at D0 with P20 increased IC and compliance when applied to saline-treated but not endotoxin-exposed pups. At D7, P24 ventilation of endotoxin-exposed pups increased elastance, bronchoalveolar lavage protein content, and IL-1b and TEN-C mRNA expression in comparison to the saline group. In summary, antenatal endotoxin exposure alters lung mechanics at birth and 1 week of life and increases susceptibility to VILI as observed in lung mechanics, alveolocapillary barrier injury, and inflammatory mRNA expression. We speculate that antenatal inflammation primes the lung for a more marked VILI response, suggesting an adverse synergistic effect of antenatal and postnatal exposures.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Mandell, Mattson, Seedorf, Ryan, Gonzalez, Wallbank, Bye, Abman and Smith.)
Databáze: MEDLINE
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