chapter  4
28 Pages

Acute Passive and Active Changes in Microvascular Permeability During Lung Distention

WithJames C. Parker, Takashige Miyahara, Mircea Anghelescu

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.