title: Sodium metabisulphite causes epithelial damage and increases sheep tracheal blood flow and permeability.
abstract: Inhaled sodium metabisulphite (MBS) causes bronchoconstriction, cough and microvascular leakage. We have studied its effects on tracheal blood flow, potential difference (PD) and the permeability from tracheal lumen to venous blood of a low molecular weight hydrophilic tracer, 99mtechnetium-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA) in anaesthetized sheep. Flow was measured in tracheal artery and blood from a cannulated tracheal vein collected for 5 min periods. The tracheal lumen was filled with Krebs-Henseleit solution (KH) containing 99mTc-DTPA for six to eight 15 min periods. During the third or fourth period, MBS (1, 20 or 100 mM) was washed into the tracheal lumen for 15 min. MBS increased tracheal blood flow (venous flow (Q'v), 5-10 min MBS exposure period: 1 mM -9 +/- 18% (n = 3); 20 mM +16 +/- 5% (n = 5; p < 0.05); 100 mM +43 +/- 13% (n = 5; p < 0.05). It decreased PD in a concentration-dependent way. Venous 99mTc-DTPA concentration increased progressively to +266 +/- 176 and +958 +/- 321% 25-30 min after exposure to 20 and 100 mM MBS, respectively (p < 0.05 for both). These effects were not blocked by luminal frusemide (3-7 mM) or flurbiprofen (100-500 microM). Histological sections showed changes to the epithelial cells and large intercellular spaces. Thus, luminal sodium metabisulphite increases tracheal blood flow, reduces transmural potential difference and causes tracheal epithelial damage, leading to an increase in 99mTc-labelled diethylenetriamine penta-acetic acid permeability.
authors.affiliation: Dept of Physiology, St George's Hospital Medical School, London, UK.
authors.forename: U M
authors.initials: UM
authors.lastname: Wells
authors.forename: Z
authors.initials: Z
authors.lastname: Hanafi
authors.forename: J G
authors.initials: JG
authors.lastname: Widdicombe
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000494:pharmacology; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects*; D012756:Sheep; D013447:Sulfites / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea / Q000098:blood supply / Q000473:pathology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013447:Sulfites; D005480:Flurbiprofen; C030981:metabisulfite; D005665:Furosemide