title: Localized acid instillation by a wedged-catheter method reveals a role for vascular gap junctions in spatial expansion of acid injury.
abstract: Acid aspiration is a major cause of acute lung injury. However, the mechanisms that underlie this spatial expansion of the injury remain undefined. In current animal models of acid injury, intratracheal acid instillation replicates the lung injury. However intratracheal instillation causes a global effect, precluding studies of how the injury spreads. Here, we report an airway catheter-based method for localized acid delivery in the isolated blood-perfused rat lung. We co-instilled hydrochloric acid with evans blue through the catheter into one lung and determined blood-free extravascular lung water in tissue samples from regions that either received, or did not receive the instilled acid. Tissue samples from the noncatheterized contralateral lung were used as controls. Lung water increased both in the regions that received acid, as well as in adjacent regions that did not. Pretreating the lung with vascular infusions of the gap junctional blocker, glycerrhetinic acid, blunted the acid-induced lung water increase at the adjacent regions. These findings indicate that endothelial gap junction communication causes spread of lung injury from regions that were directly acid injured, to adjacent sites that did not directly receive acid. Our new method for establishing localized acid injury provides evidence for a novel role for vascular gap junctions in the spatial expansion of acid injury.
authors.affiliation: Departments of Physiology and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Parthasarathi
authors.forename: Jahar
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002404:Catheterization; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006851:Hydrochloric Acid