In flexiVent, vivoFlow
Conscious measurements allow researchers to quantify effects
of diseases or therapeutic interventions on the drive to breathe, also referred to
as “Pumping apparatus” 1. The breathing drive involves different
components that regulate respiration including respiratory muscles, the central nervous system, and
chemo/mechano-receptors. Outcomes such as tidal volume, respiratory rate,
minute volume, inspiratory, expiratory, and apneic periods are particularly
useful in safety pharmacology studies, and research into sleep and neuromuscular diseases. Whole body plethysmography (WBP) is the
simplest and least invasive approach that permits conscious in vivo measurements. However, researchers
must consider the inherent limitations of WBP2 in regards to the
accuracy of breathing volumes and assessment of airway hyperresponsiveness. Other techniques such as
head-out plethysmography (HOP) or double chamber plethysmography (DCP) are
often useful in providing a more accurate and validated assessment of the lung
function.

EF50 – a valid
indicator of airway response

In difference to WBP, where the subject is freely moving within a chamber,
HOP/DCP measurements are acquired in restrained subjects, allowing true inspiratory
and expiratory flow measurements and their corresponding parameters. One such outcome,
the tidal mid-expiratory flow (EF50), is particularly interesting as it has
been described and validated over the last 20 years as an index of flow
limitation and airway obstruction.  The
parameter is calculated on a breath-by-breath basis during spontaneous tidal
breathing and typically decreases in presence of airflow obstruction.

Other Applications

 
EF50 is often used in respiratory safety pharmacology
studies performed under the ICH 7AS guidelines, where the HOP technique is a
standard for conscious lung function assessment.  However, the parameter can also be obtained with DCP, allowing for exposure to nebulized substances
and/or the ability to record nasal and thoracic flows separately.  Using this approach, EF50 can also be used to
describe airway responsiveness changes to broncho-active substances in
conscious mice, either naïve or allergic.
Since EF50 does not provide a direct measurements of
resistance, it is generally accepted that any change in this parameter would be
followed by a comprehensive lung function assessment such as that provided by
the flexiVent system.

References

  • 1Murphy DJ, 2013. Respiratory safety pharmacology
    – Current practice and future direction. Regulatory Toxicology and Pharmacology
    69. DOI: 10.1016/j.yrtph.2013.11.010
  • 2Bates et al., 2003. Measuring lung function in
    mice: the phenotyping uncertainty principle.
    J. of Appl. Physiology 1297-306. DOI: 10.1152/japplphysiol.00706.2002
  • Hoymann HG, 2012. Lung function measurements in rodents in
    safety pharmacology. Frontiers
    in pharmacology 3: article 156. doi: 10.3389/fphar.2012.00156.
  • Glaab T et
    al., 2001. Tidal midexpiratory flow as a measure of airway
    hyperresponsiveness in allergic mice. Am J Physiol Lung Cell Mol Physiol 280:
    L565-573.
  • Vijayaraghavan R et al., 1993. Characteristic modifications
    of the breathing pattern in mice to evaluate the effects of airborne chemicals
    on the respiratory tract. Arch Toxicol 67: 478-490.
  • Walker JKL et al., 2013. Assessment of murine lung mechanics
    outcome measures: alignment with those made in asthmatics. Frontiers in
    pharmacology 3: article 491. doi: 10.3389/fphar.2012.00491.

 

 

 

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