The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse

Mahesh Dharmakumara, G Kim Prisk, Simon G Royce, Merryn Tawhai, Bruce R Thompson

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Abstract

Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (Vo2). 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 Vo2 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 Vo2 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 Vo2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.
Original languageEnglish
Pages (from-to)1049 - 1054
Number of pages6
JournalJournal of Applied Physiology
Volume117
Issue number9
DOIs
Publication statusPublished - 2014

Cite this

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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 (Vo2). 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 Vo2 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 Vo2 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 Vo2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.",
author = "Mahesh Dharmakumara and Prisk, {G Kim} and Royce, {Simon G} and Merryn Tawhai and Thompson, {Bruce R}",
year = "2014",
doi = "10.1152/japplphysiol.00543.2014",
language = "English",
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pages = "1049 -- 1054",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
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The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse. / Dharmakumara, Mahesh; Prisk, G Kim; Royce, Simon G; Tawhai, Merryn; Thompson, Bruce R.

In: Journal of Applied Physiology, Vol. 117, No. 9, 2014, p. 1049 - 1054.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The effect of gas exchange on multiple-breath nitrogen washout measures of ventilation inhomogeneity in the mouse

AU - Dharmakumara, Mahesh

AU - Prisk, G Kim

AU - Royce, Simon G

AU - Tawhai, Merryn

AU - Thompson, Bruce R

PY - 2014

Y1 - 2014

N2 - Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (Vo2). 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 Vo2 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 Vo2 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 Vo2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.

AB - Inert-gas washout measurements using oxygen, in the lungs of small animals, are complicated by the continuous process of oxygen consumption (Vo2). 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 Vo2 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 Vo2 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 Vo2-to-Va ratio in this small animal, and not due to inhomogeneity within the airways.

UR - http://jap.physiology.org/content/117/9/1049

U2 - 10.1152/japplphysiol.00543.2014

DO - 10.1152/japplphysiol.00543.2014

M3 - Article

VL - 117

SP - 1049

EP - 1054

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 9

ER -