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

George Simbruner; Rashmi A. Mittal; Johan Smith; Gerd Maritz; Johan van Rensberg; Bernadette Simbruner; Andreas Holzinger

doi:10.1055/s-2007-970177

American Journal of Perinatology, Table of Contents

Am J Perinatol 2007; 24(3): 149-159
DOI: 10.1055/s-2007-970177

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

George Simbruner¹ , Rashmi A. Mittal¹ , Johan Smith² , Gerd Maritz³ , Johan van Rensberg⁴ , Bernadette Simbruner⁵ , Andreas Holzinger⁶

¹Department of Neonatology, Medical University Innsbruck, Innsbruck, Austria
²Department of Pediatrics, University of Stellenbosch, Tygerberg, South Africa
³Department of Medical Biosciences, University of Western Cape, Bellville, South Africa
⁴Department of Anesthesiology, Tygerberg Hospital, South Africa
⁵Medical University Vienna, Vienna, Austria
⁶Ludwig-Maximilians University, Munich, Germany

Abstract

ABSTRACT

The 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 [aaDo ₂]) 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.

KEYWORDS

Ventilator-induced lung injury - inflammation - interleukins - gene transcription - animals

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References

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George SimbrunerM.D.

Professor of Pediatrics, Department of Neonatology and Neonatal Intensive Care; University Children's Hospital

Anichstrasse 35, A-6020, Innsbruck, Austria