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 lungs ventilated at different peak inflation pressures (PIPs) with (gadolinium group) and without (control group) infusion of 20 microM gadolinium chloride, an inhibitor of endothelial stretch-activated cation channels. Microvascular permeability was assessed by using the capillary filtration coefficient (Kfc), a measure of capillary hydraulic conductivity. Kfc was measured after ventilation for 30-min periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In control lungs, Kfc increased significantly to 1.8 and 3.7 times baseline after 30 and 35 cmH2O PIP, respectively. In the gadolinium group, Kfc was unchanged from baseline (0.060 +/- 0.010 ml . min-1 . cmH2O-1 . 100 g-1) after any PIP ventilation period. Pulmonary vascular resistance increased significantly from baseline in both groups before the last Kfc measurement but was not different between groups. These results suggest that microvascular permeability is actively modulated by a cellular response to mechanical injury and that stretch-activated cation channels may initiate this response through increases in intracellular calcium concentration.
Parker
J C
JC
Departments of Physiology and Pathology, University of South Alabama, Mobile, Alabama 36688, USA. Jarker@jaguar1.usouthal.edu
Ivey
C L
CL
Tucker
J A
JA
D000399:Air Pressure; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015824:Blood-Air Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000502:physiology; D005682:Gadolinium / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats
D005682:Gadolinium