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

Frontiers in Physiology

Courtney Mattson¹  Alison Wallbank¹  Tania Gonzalez³  Sharon Ryan³  Erica W. Mandell³  Elisa M. Bye³  Bradford J. Smith⁴  Gregory Seedorf⁴  Steven H. Abman⁴ 

[1] Department of Bioengineering, College of Engineering, Design, and Computing, University of Colorado Denver

[2]  Anschutz Medical Campus, Aurora, CO, United States;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;Division of Pediatric Pulmonary and Sleep Medicine, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States;

关键词: newborn rat ventilation;    lung development;    endotoxin;    lung structure;    ventilator induced lung injury;    antenatal exposure;   

DOI  :  10.3389/fphys.2020.614283

来源: DOAJ

【 摘 要 】

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 cmH2O]; P20 ventilation [plateau pressure (Pplat) = 20 cmH2O, PEEP = 0]; or P24 ventilation (Pplat = 24 cmH2O, 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.

【 授权许可】

Unknown