Jc. Parker et al., GADOLINIUM PREVENTS HIGH AIRWAY PRESSURE-INDUCED PERMEABILITY INCREASES IN ISOLATED RAT LUNGS, Journal of applied physiology, 84(4), 1998, pp. 1113-1118
To determine the initial signaling event in the vascular permeability
increase after high airway pressure injury, we compared groups of lung
s ventilated at different peak inflation pressures (PIPs) with (gadoli
nium group) and without (control group) infusion of 20 mu M gadolinium
chloride, an inhibitor of endothelial stretch-activated cation channe
ls. Microvascular permeability was assessed by using the capillary fil
tration coefficient (K-fc), a measure of capillary hydraulic conductiv
ity. K-fc was measured after ventilation for 30-min periods with 7, 20
, and 30 cmH(2)O PIP with 3 cmH(2)O positive end-expiratory pressure a
nd with 35 cmH(2)O PIP with 8 cmH(2)O positive end-expiratory pressure
. In control lungs, K-fc increased significantly to 1.8 and 3.7 times
baseline after 30 and 35 cmH(2)O PIP, respectively. In the gadolinium
group, K-fc was unchanged from baseline (0.060 +/- 0.010 ml.min(-1).cm
H(2)O(-1).100 g(-1)) after any PIP ventilation period. Pulmonary vascu
lar resistance increased significantly from baseline in both groups be
fore the last K-fc measurement but was not different between groups. T
hese results suggest that microvascular permeability is actively modul
ated by a cellular response to mechanical injury and that stretch-acti
vated cation channels may initiate this response through increases in
intracellular calcium concentration.