At its core, the flexiVent is a computer-controlled, precision piston pump that can intersperse mechanical ventilation with a variety of volume and pressure controlled manoeuvres to obtain accurate, reproducible measurement of respiratory mechanics.
A basic flexiVent system includes the following:
Base unit: houses the motor, optical position sensor and electronics.
Module(s): interchangeable units, allowing a range of subjects to be studied.
flexiWare software: manages the collection, analysis, graphing and archiving of data.
The forced expiration extension (FEV) extension is a hardware add-on that allows the study of expiratory flow limitations, analogous to spirometry, a widely known clinical pulmonary test measuring volumes and flows expired by patients that is used to confirm a diagnostic of respiratory disease or follow treatment. The FEV extension permits the generation of flow-volume loops and its associated parameters by rapidly exposing the subject’s airway opening to negative pressure, referred to as Negative Pressure Forced Expirations (NPFE). The NPFEs can be interspersed with all other flexiVent measurements, uniquely combining the forced expiratory and forced oscillation measurements into a single platform.
During the NPFE manoeuvre, the subject is inflated to total lung capacity (TLC) state and then rapidly switched to a negative pressure reservoir to essentially draw the air out of its lungs. The FEV extension’s outcomes include flow-volume loops, peak expiratory flow (PEF), forced vital capacity (FVC), forced expired volumes (FEVx) and flows (FEFx) at user-defined times are automatically displayed/ calculated by the software.
Available for Mice, rats and ferrets
The FEV extension readily connects to most existing flexiVent systems for use in mice, rats and ferrets. It includes a plethysmograph chamber with an integrated sensor to measure chest flow, a negative pressure reservoir with its controller, and two additional valves. Upon completion of the NPFE, the flexiWare software immediately displays flow-volume loops and automatically calculates all pertinent volume and flow parameters (FEVx, FEFx, FVC, PEF).
Towards Clinical Studies
The addition of FEV offers a means to more directly assess expiratory flow limitation. Although NPFE manoeuvres are obtained under conditions that differ substantially from clinical spirometry, they may provide a useful cross-species correlation for drug development studies. A recent publication by Devos et al, characterized forced expiration measurements in some well-established mouse models of lung diseases, which specific phenotypes were confirmed by a concomitant respiratory mechanics assessment. The researchers observed that disease-induced changes in forced expiration-related charts and parameters were generally similar to what was observed in the clinic. For example, when compared to a control group of healthy mice.
Mice with fibrosis exhibited a typical restrictive profile, with a reduced
PEF & FVC and a normal FEV0.1/FVC ratio.
Mice with emphysema displayed a decrease in PEF characteristic of an obstructive phenotype.
Mice presenting an acute lung injury had significantly reduced PEF.
Mice with features of asthma showed a decrease in FEV0.1 following methacholine challenges.
Preclinical research often looks for translational outcomes, therefore this extension is already cited in a number of different applications, including COPD and Cystic Fibrosis. A few selected articles are outlined below for reading interest:
The immunomodulatory effects of diesel exhaust particles in asthma. De Homdedeu, M., et al. (2020). Environmental Pollution, 263, 114600
Airway Resistance Caused by Sphingomyelin Synthase 2 Insufficiency in Response to Cigarette Smoke. Gupta, G., et al. (2019). American Journal of Respiratory Cell and Molecular Biology, 62(3)
Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity. Yamashita, Y., et al. (2019). Bioorganic & Medicinal Chemistry: 27(5): 3339-3346
Repeated Exposure to Streptococcus pneumoniae Exacerbates Chronic Obstructive Pulmonary Disease. Gou, X., et al. (2019). American Journal of Pathology, 189(9): 1711-1720
Forced expiration measurements in mouse models of obstructive and restrictive lung diseases. Devos, F.C et al. (2017). Respiratory Research, 18(123)
Forced Expiratory Volume (FEV) Measurements in Mouse Models of Lung Disease. Vanoirbeek, J. (2016). American Journal of Respiratory and Critical Care Medicine, 193, A5957
Effects of nintedanib on the microvascular architecture in a lung fibrosis model. Ackermann, M., et al. (2016). Angiogenesis, 1-14
Chemically modifed hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis. Haque, A.K.M et al. (2018). Scientific Reports, 8:16776
Azithromycin inhibits constitutive airway epithelial sodium channel activation in vitro and modulates downstream pathogenesis in vivo. Fujikawa, H., et al. (2020). Biological and Pharmaceutical Bulletin, 43(4): 725-730
Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function. Fujikawan, H., et al. (2020). Antioxidants, 9(5): 10.3390/antiox9050387
Idelalisib induces apoptosis in the lymphoid tissues and impairs lung function in mice. George, J.A., et al. (2019). Journal of Chemotherapy, 32(2), 88-9
The flexiVent can be tightly integrated with the Aeroneb ultrasonic nebulizer to deliver aerosols deep into the lungs. To add an Aeroneb to your flexiVent system, a suitable adapter is required that mounts into the module.
flexiWare offers complete control over the timing of the challenge, the nebulization rate and the manner in which aerosolization is synchronized with ventilation. Furthermore, dose response curves can be automatically generated. The software estimates the dose delivered to the subject and can plot it against delivered dose or concentration, in addition to characterizing the losses due to rain-out.
The flexiVent’s control and standardization of experimental conditions (e.g. respiratory rate, tidal volume, PEEP, volume history) is directly beneficial to the imaging application by eliminating motion artifacts. It offers the ability to compare and correlate structural information obtained from lung images with lung function data obtained directly from the flexiVent.
We offer turn-key packages to integrate with a variety of micro-CT scanners on the market. The package includes a custom gating cable, specialized accessories for connecting the subject through the scanner’s instrument channels, as well as other necessary connectors, adapters and flexiWare software templates.
Sensors to monitor the subject’s vital signs can easily be integrated with the flexiVent system. The EKG transducer monitors the subject’s heart rate by connecting to the subject’s limbs. The connection is ensured with the use of sub-cutaneous needles. The invasive saline-filled blood pressure transducer allows for observation of changes in blood pressure. Body temperature can be measured with the rectal sensor. Oxygen saturation can be monitored using Starr life Science’ MouseOX pulse oxymetry transducer. Vital signs are displayed in the flexiWare software in real-time and may be recorded continuously or with every mechanics measurement.
While the flexiVent is typically utilized to assess the mechanical properties of the lower airways, it can also be used for accurate measurements of nasal obstruction. As previously reported, this approach provides a means to reliably and directly assess upper airway resistance in disease models.
Similar to respiratory mechanics measurements of the lower airways, the flexiVent uses the forced oscillation technique to deliver a small amplitude test signal to the upper airways. Nasal resistance is then derived by the operating software from the pressure-flow relationship as described in the single compartment model. At the moment, these measurements are described in allergic rhinitis pre-clinical research, one of the most common allergic diseases worldwide affecting people of all ages.
SCIREQ will provide suitable accessories with the original purchase of your basic system or any of the extensions. Some items are considered disposable and will need to be replaced over time or after heavy use.
For the flexiVent, we offer calibration accessories such as pressure manometers, flow meters and test loads. Wetted components including the Aeroneb, cannulae, tubing, O-rings, valves and filters are available. Computers, cables, power supplies and tools may also be acquired as needed.