Wednesday, November 30, 2016

Lung Function in Conscious Subjects

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.



Wednesday, November 9, 2016

MEET WITH US IN SAN DIEGO AT SOCIETY FOR NEUROSCIENCE!

The emka & SCIREQ team will be attending the Society for Neuroscience 2016 conference in San Diego! We will present and demonstrate our wide range of preclinical instruments for neuro, pulmonary and cardio studies. Come by booth #3533 and speak with our experienced team about our solutions for physiology, pharmacology and toxicology research.

 A special focus on optogenetics

Optogenetic studies targeting respiratory centers in the brain stem can be paired with whole body plethysmography (WBP) to measure pulmonary function.

» Our WBP chambers pair with fibre optic cables to offer real-time assessment of lung function changes resulting from optical manipulation.
» Does not require anaesthetics, which can depress the neural-network controlling respiration.
» Conscious, freely moving subjects that have the ability to respond to real-time optical challenges.
» Swivel/tether system for measurement of other physiological parameters (ECG, EEG) or blood sampling following injections.
» Easily integrated with gas challenges (CO2/O2) to further induce or inhibit signaling pathways.
» Measures ventilatory parameters: Respiratory Rate (RR), estimated Tidal Volume (VT), Minute Ventilation (V) or Periodic breathing

Telemetry

easyTEL implantable system transmits physiological data from conscious freely moving laboratory animals. Our range of implants offers the ability to record the following parameters, depending on your study needs:

» Biopotential (ECG, EEG, EMG)
» Blood pressure
» Temperature
» Activity from acceleration

Click here to schedule a meeting with one of our specialists during SFN 2016.

Friday, November 4, 2016

THANK YOU UNIVERSITY OF WISCONSIN-MADISON!


Thank you to Drs. Teodorescu and Broytman at the University of Wisconsin-Madison for hosting an introductory workshop and seminar on Lung Function Measurements in Rodents. Research and Development Manager, Liah Fereydoonzad, and Application Specialist, John Morse, worked with participants at the workshop to perform an automated dose-response study in an allergic model with the flexiVent.


The seminar presentation discussed a variety of solutions for in vivo lung physiology, from non-invasive whole body plethysmography to detailed respiratory mechanics with the flexiVent. An application specific approach to the outcomes of each method was presented, as the detail of outcomes is determined by the invasiveness of the technique1.




Please contact us to find out more about lung function measurements or if you are interested in hosting a similar event! www.scireq.com

1 J. H. Bates and C. G. Irvin, "Measuring lung function in mice: the phenotyping uncertainty principle.," Journal of Applied Physiology, vol. 94, p. 1297, 2003.