American journal of perinatology
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The purpose of this study was to characterize the effects of doubling minute ventilation (either by doubling ventilator frequency [Freq] or tidal volume [V T]) and of normal minute ventilation prolonged to 12-fold duration, synchronously at biophysical, biochemical/cellular, histological, and transcriptional levels in a model of mild lung injury. A prospective, randomized study was performed on adolescent New-Zealand white rabbits. The rabbits were randomly assigned to one of the following groups: control (normal minute ventilation for 0.5 hours); 1 x V T, 12-fold prolongation at normal V T (normal minute ventilation for 6 hours [12 x 0.5 hours]); 2 x Freq at normal V T (double minute ventilation for 6 hours); and 2 x V T at normal Freq (double minute ventilation for 6 hours). ⋯ At the transcriptional level, lung IL-8 mRNA expression increased 11-fold in the 2 x V T group ( P = 0.002), 9-fold ( P = 0.02) in the 2 x Freq group, and 4-fold in the 1 x V T group as compared with control. Not only doubling V T, but also doubling Freq at normal V T injures the lung significantly, although to a lesser extent. A concept of weighted risk for increases of V T and Freq is proposed.