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Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow

Abstract

Introduction

The mechanism of fast inspiratory flow rate (VI′) induced lung injury is unclear. As fast VI′ increases hysteresis, a measure of surface tension at the air–liquid interface, surfactant release or function may be important. This experimental study examines the contribution of impaired surfactant release or function to dynamic-VILI.

Methods

Isolated perfused lungs from male Sprague Dawley rats were randomly allocated to four groups: a long or short inspiratory time (Ti = 0.5 s; slow VI′ or Ti = 0.1 s; fast VI′) at PEEP of 2 or 10 cmH2O. Tidal volume was constant (7 ml/kg), with f = 60 breath/min. Forced impedance mechanics (tissue elastance (Htis), tissue resistance (Gtis) and airway resistance (Raw) were measured at 30, 60 and 90 min following which the lung was lavaged for surfactant phospholipids (PL) and disaturated PL (DSP).

Results

Fast VI′ resulted in a stiffer lung. Concurrently, PL and DSP were decreased in both tubular myelin rich and poor fractions. Phospholipid decreases were similar with PEEP. In a subsequent cohort, laser confocal microscopy-based assessment demonstrated increased cellular injury with increased VI′ at both 30 and 90 min ventilation.

Conclusion

Rapid VI′ may contribute to ventilator induced lung injury (VILI) through reduced surfactant release and/or more rapid reuptake despite unchanged tidal stretch.

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Acknowledgements

The authors gratefully acknowledge Heather Barr, MSc, and Darren Kennedy, BSc for technical assistance, and Dr Jennifer Clarke for assistance with confocal imaging. This project was supported by the National Health and Medical Research Council (Grant #275565), the Australian and New Zealand College of Anaesthetists (Grant # 06/018) and the Flinders Medical Centre Foundation.

Funding

This project was supported by the National Health and Medical Research Council (Grant #275565), the Australian and New Zealand College of Anaesthetists (Grant # 06/018) and the Flinders Medical Centre Foundation.

Author information

ADB, DLD conceived and designed the analysis. MK, KG collected the data. DLD performed the analysis. AB, DLD wrote the paper. AB, MK, KG, DLD revised and approved the final manuscript.

Correspondence to Dani-Louise Dixon.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All experiments were approved by the Flinders University Animal Welfare Committee and performed according to the National Health and Medical Research Council of Australia Guidelines on Animal Experimentation.

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Bersten, A.D., Krupa, M., Griggs, K. et al. Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow. Lung 198, 43–52 (2020). https://doi.org/10.1007/s00408-019-00317-1

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Keywords

  • Lung mechanics
  • Ventilator induced lung injury
  • Cytokines
  • Inspiratory flow rate
  • Surfactant
  • Confocal microscopy