Did you know...

...that mechanical lung ventilation can induce lung injury?

Mechanical ventilation is the process of supporting breathing, by manual or mechanical means, when normal breathing is inefficient or has stopped [1].  The concept of mechanical ventilation originated in 1543 with Andreas Vesalius' demonstration of lung inflation using a reed inserted into the tracheas of pigs and dogs (Figure 1) [2].  Although technology has advanced significantly to reduce morbidity and mortality for critically ill patients, the use of mechanical ventilation is not without risk. Lung injury induced by mechanical means is referred to as ventilator-induced lung injury (VILI) [3].  VILI increases endothelial and epithelial permeability leading to pulmonary edema and compromised gas exchange [4-6].  While the level of airway pressure applied, lung volume changes, and the rate and duration of ventilation are known factors that contribute to VILI, [5, 6] mechanisms underlying the relationship of these treatment modalities to lung damaging events remain poorly understood.

Several theories have attempted to explain the mechanistic basis of VILI. In 1957, the first theory, the stretched-pore hypothesis suggested that vascular distention opened endothelial intercellular junctions increasing fluid and protein leak sufficient to compromise lung function [7].  The stress failure hypothesis, presented in 1991, proposed that pressure induced tensile failure of capillary endothelium and basement membrane resulted in hemorrhage and fluid leak [8].  The most recent theory, the stretch-recoil hypothesis, proposed by Parker and colleagues in 1998 introduced the concept that active cellular components were involved in the development of VILI [9, 10]. This hypothesis predicted that calcium entry played a critical role in the microvascular permeability response. Building on an idea developed in the 1980s showing that elevations in cytosolic calcium caused increased microvessel permeability [11], Parker et al provided evidence that elevated cytosolic calcium was also seen upon mechanical stretch of the endothelium. Their stretch-recoil hypothesis stated that calcium entry through stretch-activated cation channels initiated signaling pathways which increased tension of actin-myosin fibrils resulting in retraction of endothelial cell margins, loss of barrier integrity, and increased permeability [9, 12]. The stretch-recoil hypothesis established the new concept that cellular signaling mechanisms were involved in development of VILI.  Although further studies are needed to resolve the molecular basis proposed for VILI, the stretch-recoil hypothesis provides an impetus for developing new therapeutic strategies that reduce the risk of mechanical injury.


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  8. Parker JC. Inhibitors of myosin light chain kinase and phosphodiesterase reduce ventilator-induced lung injury. Journal of Applied Physiology. Dec 2000;89(6):2241-2248.
  9. Parker JC, Ivey CL, Tucker JA. Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs. Journal of Applied Physiology. Apr 1998;84(4):1113-1118.
  10. R.H. A. Protein Tyrosine Phosphorylation Modulates Microvessel Permeability In Frog Mesentery. Microcirculation. 1996;3(2):245-247.
  11. He P, Pagakis SN, Curry FE. Measurement of cytoplasmic calcium in single microvessels with increased permeability. American Journal of Physiology. May 1990;258(5 Pt 2):H1366-1374.
  12. He P, Curry FE. Differential actions of cAMP on endothelial [Ca2+]i and permeability in microvessels exposed to ATP. American Journal of Physiology. Sep 1993;265(3 Pt 2):H1019-1023.

Author: Christina Barry
Chief Editor: Judy Creighton, Ph.D. April 2010

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