GADOLINIUM PREVENTS HIGH AIRWAY PRESSURE-INDUCED PERMEABILITY INCREASES IN ISOLATED RAT LUNGS

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.