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Bleomycin-induced acute lung injury in the rat does not influence pulmonary vascular responsiveness in vitro
D E Crawley1, D G McCormack, T W Evans
1Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Objective:
To investigate the effects of the intratracheal and iv administration of bleomycin on the contraction and endothelially dependent vasodilation of rat pulmonary arteries in vitro.
Design:
Prospective pharmacologic study.
Setting:
National Heart and Lung Institute, London, UK.
Interventions:
Intratracheal saline, intratracheal and iv bleomycin.
Measurements And Main Results:
Rats treated with intratracheal bleomycin developed a significant increase in mean lung wet/dry weight ratio (5.6 +/- 0.4 [SEM] vs. 3.9 +/- 0.1, p less than .05) when compared with saline-treated control animals, confirming the development of pulmonary edema. However, these rats displayed normal relaxant responses to the endothelially dependent vasodilator acetylcholine and a normal contractile response to phenylephrine in vitro. Intravenous bleomycin had no effect on either wet/dry weight ratio or the response to either drug.
Conclusions:
Despite evidence for the loss of endothelial integrity that characterizes lung injury after intratracheal bleomycin, isolated pulmonary artery rings in vitro showed no loss of endothelial cell function. The role of the endothelium in modulating pulmonary ventilation/perfusion matching after lung injury is unclear.