title: High-resolution spatial measurements of ventilation-perfusion heterogeneity in rats.
abstract: This study was designed to validate a high-resolution method to measure regional ventilation (VA) in small laboratory animals, and to compare regional Va and perfusion (Q) before and after methacholine-induced bronchoconstriction. A mixture of two different colors of 0.04-microm fluorescent microspheres (FMS) was aerosolized and administered to five anesthetized, mechanically ventilated rats. Those rats also received an intravenous injection of a mixture of two different colors of 15-microm FMS to measure regional blood flow (Q). Five additional rats were labeled with aerosol and intravenous FMS, injected with intravenous methacholine, and then relabeled with a second pair of aerosol and intravenous FMS colors. After death, the lungs were reinflated, frozen, and sequentially sliced in 16-microm intervals on an imaging cryomicrotome set to acquire signal for each of the FMS colors. The reconstructed lung images were sampled using randomly placed 3-mm radius spheres. Va within each sphere was estimated from the aerosol fluorescence signal, and Q was estimated from the number of 15-microm FMS within each sphere. Method error ranged from 6 to 8% for Q and 0.5 to 4.0% for Va. The mean coefficient of variation for Q was 17%, and for Va was 34%. The administration of methacholine altered the distribution of both VA and Q within lung regions, with a change in Va distribution nearly twice as large as that seen for Q. The methacholine-induced changes in Va were not associated with compensatory shifts in Q. Cryomicrotome images of FMS markers provide a high-resolution, anatomically specific means of measuring regional VA/Q responses in the rat.
authors.affiliation: Department of Medicine, University of Washington, and University Hospital, Box 356522, Seattle, WA 98195-6522, USA. tomrobt@u.washington.edu
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Robertson
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Krueger
authors.forename: Wayne J E
authors.initials: WJ
authors.lastname: Lamm
authors.forename: Robb W
authors.initials: RW
authors.lastname: Glenny
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005629:Frozen Sections; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008863:Microspheres; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015203:Reproducibility of Results; D012121:Respiration, Artificial; D014692:Ventilation-Perfusion Ratio
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D005456:Fluorescent Dyes; D016210:Methacholine Chloride