Lung fluid absorption is induced in preterm guinea pigs ventilated with low tidal volumes

Abstract

ABSTRACTThe objective of this study was to determine if low tidal volume (Vt) ventilation was beneficial when ventilating preterm fetuses. The authors ventilated preterm guinea pig fetuses at gestation day (GD) 67, 3 days before birth, newborn, and 10-day-old (PD10) guinea pigs with low Vt (6 mL/kg body weight [bw]) and compared them to age-matched fetuses/animals ventilated with higher potentially injurious Vt (12 mL/kg bw). Lung fluid absorption was measured after intratracheal instillation of 5% albumin in 0.9% NaCl. Low Vt ventilation stimulated lung fluid absorption when compared to higher Vt in all groups. The increased lung fluid absorption in low Vt–ventilated fetuses was associated with increased α epithelial Na channel (αEnaC) mRNA. However, αENaC and βENaC protein was unchanged over the 1-hour study. Because stretch induces mitogen-activated protein (MAP) kinase expression and MAP kinases may affect lung fluid absorption, the authors investigated if MAP kinase (MAPK) expression was affected by Vt. Extracellular signal-regulated kinase (ERK) and MAPK/ERK kinase (MEK) were phosphorylated in the higher Vt–ventilated guinea pig fetuses. This suggested that a reduced activation of MAP kinases might explain the increased lung fluid absorption in the low Vt–ventilated fetuses. Thus these data suggest that low Vt ventilation increases fetal lung fluid absorption and thus may be preferential to use clinically.