ABSTRACT
The contributing factors to lung injury that result from lung overdistention
remain a topic of intense investigation (1). However, the severity of ventilator-induced lung injury (VILI) has been generally recognized to be both
time and pressure dependent in experimental studies as well as in clinical
settings (2-4). Yoshikawa et al. (5) recently observed a size-selective alveo-
lar-capillary transport of proteins of different hydrodynamic radii, which
was dependent upon peak inflation pressures (PIP) and ventilation time.
Fluxes of Clara cell secretory protein (CCSP; 1.9 nm) from airway fluids
to plasma, and albumin (3.6 nm) and immunoglobin (5.6 nm) from plasma
to bronchoalveolar lavage (BAL) fluid exhibited increases that were both time and pressure related (Fig. 1). Progressively higher PIP levels reduced
the restriction of successively larger proteins (Fig. 1A), but size restriction
was also lost as ventilation time at an injurious PIP (55 cmH2O) was pro-
longed even though significant clearance rates of all three proteins occurred
even at 30 minutes (Fig. 1B). Although the time course of the interaction of
vascular permeability, signaling molecules, and the inflammatory response
remains controversial (6), most studies indicate a rapid initial increase in
vascular permeability during mechanical strain of the lung. The rapidity
of this increase appears to precede development of the cytokine cascade
and recruitment of inflammatory cells, which may then amplify the lung
injury (7,8). Ventilation of isolated perfused lungs of dog, rats, mice, and rabbits with high PIP for periods of only 20 minutes produce significant
increases in vascular permeability as assessed by filtration coefficients
Figure 1 Increases in plasma and BAL concentrations of CCSP (CCSP, 1.9 nm radius); albumin (3.6 nm radius); and IgG (5.6 nm radius) as a function of PIP (A) and ventilation time at 55 cmH2O (B). Abbreviations: BAL, bronchoalveolar lavage; CCSP, Clara cell secretory protein; IgG, immunoglobin; PIP, peak inflation pressure. Source: From Ref. 5.
