title: The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse.
abstract: Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (V̇o2). The multiple-breath nitrogen washout (MBNW) technique uses the alveolar slope to determine measures of ventilation inhomogeneity in the acinar (Sacin) and conducting (Scond) airway regions, as well as overall inhomogeneity, as determined by the lung clearance index (LCI). We hypothesized that measured ventilation inhomogeneity in the mouse lung while it is alive is in fact an artifact due to the high V̇o2 in proportion to alveolar gas volume (Va), and not ventilation inhomogeneity per se. In seven male C57BL/6 mice, MBNW was performed alive and postmortem to derive measures with and without the effect of gas exchange, respectively. These results were compared with those obtained from an asymmetric multibranch point mathematical model of the mouse lung. There was no statistical difference in Sacin and LCI between alive and postmortem results (Sacin alive = 0.311 ± 0.043 ml(-1) and Sacin postmortem = 0.338 ± 0.032 ml(-1), LCI alive = 7.0 ± 0.1 and LCI postmortem = 7.0 ± 0.1). However, there was a significant decrease in Scond from 0.086 ± 0.005 ml(-1) alive to 0.006 ± 0.002 ml(-1) postmortem (P < 0.01). Model simulations replicated these results. Furthermore, in the model, as V̇o2 increased, so did the alveolar slope. These findings suggests that the MBNW measurement of Scond in the mouse lung is confounded by the effect of gas exchange, a result of the high V̇o2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, and Monash University, Melbourne, Victoria, Australia; m.dharmakumara@alfred.org.au.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Dharmakumara
authors.affiliation: Departments of Medicine and Radiology, University of California, San Diego, California;
authors.forename: G Kim
authors.initials: GK
authors.lastname: Prisk
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia; and.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Royce
authors.affiliation: Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Merryn
authors.initials: M
authors.lastname: Tawhai
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, and Monash University, Melbourne, Victoria, Australia;
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Thompson
mesh_terms: D000818:Animals; D008168:Lung / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009584:Nitrogen / Q000032:analysis*; D012123:Pulmonary Ventilation / Q000502:physiology*; D012119:Respiration; D012129:Respiratory Function Tests; D013147:Spirometry; D014109:Total Lung Capacity / Q000502:physiology
chemical_list: D009584:Nitrogen
keywords: alveolar slope; mouse lung; multiple-breath nitrogen washout; oxygen consumption; ventilation inhomogeneity