Effects of duration and amount of lung stretch at biophysical, biochemical, histological, and transcriptional levels in an in vivo rabbit model of mild lung injury

dc.contributor.authorSimbruner G.
dc.contributor.authorMittal R.A.
dc.contributor.authorSmith J.
dc.contributor.authorMaritz G.
dc.contributor.authorVan Rensberg J.
dc.contributor.authorSimbruner B.
dc.contributor.authorHolzinger A.
dc.identifier.citationAmerican Journal of Perinatology
dc.description.abstractThe purpose of this study was to characterize the effects of doubling minute ventilation (either by doubling ventilator frequency [Freq] or tidal volume [VT]) 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 × VT, 12-fold prolongation at normal VT (normal minute ventilation for 6 hours [12 × 0.5 hours]); 2 × Freq at normal VT (double minute ventilation for 6 hours); and 2 × VT at normal Freq (double minute ventilation for 6 hours). Normocapnia was maintained throughout the experiment. At the biophysical level, gas exchange (alveolar-arterial O2-tension difference [AaDO2]) deteriorated by 23, 51, and 95%, and respiratory compliance decreased by 6.0,18.4, and 26% in the 1 × VT, 2 × Freq, and 2 × VT group, respectively, during 6 hours of ventilation. Concomitantly, at the biochemical-cellular level, interleukin-8 (IL-8) in the bronchoalveolar lavage fluid increased 44-fold, 150-fold, and 275-fold (p = 0.02), respectively. The white blood cell count decreased significantly in all three intervention groups. At the histological level, the influx of leukocytes as well as the tissue water content increased in proportion to the degree of injury. At the transcriptional level, lung IL-8 mRNA expression increased 11-fold in the 2 × VT group (p = 0.002), 9-fold (p = 0.02) in the 2 × Freq group, and 4-fold in the 1 × VT group as compared with control. Not only doubling VT, but also doubling Freq at normal VT injures the lung significantly, although to a lesser extent. A concept of weighted risk for increases of VT and Freq is proposed. Copyright © 2007 by Thieme Medical Publishers, Inc.
dc.subjectinterleukin 8
dc.subjectmessenger RNA
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectchemical analysis
dc.subjectcontrolled study
dc.subjectdisease severity
dc.subjectgene expression
dc.subjectgenetic transcription
dc.subjectin vivo study
dc.subjectleukocyte count
dc.subjectlung alveolus oxygen tension
dc.subjectlung injury
dc.subjectlung lavage
dc.subjectlung minute volume
dc.subjectmuscle stretching
dc.subjectoxygen tension
dc.subjectpriority journal
dc.subjecttidal volume
dc.subjectwater content
dc.subjectBronchoalveolar Lavage Fluid
dc.subjectCarbon Dioxide
dc.subjectProspective Studies
dc.subjectPulmonary Gas Exchange
dc.subjectRandom Allocation
dc.subjectRespiration, Artificial
dc.subjectRespiratory Distress Syndrome, Adult
dc.subjectRNA, Messenger
dc.subjectTidal Volume
dc.subjectTime Factors
dc.subjectTranscription, Genetic
dc.titleEffects of duration and amount of lung stretch at biophysical, biochemical, histological, and transcriptional levels in an in vivo rabbit model of mild lung injury

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