Respiration functions through a complex network of neural controls and feedback mechanisms as the body constantly adjusts its breathing rate and tidal volume to meet respiratory metabolic demands. Varying concentrations of common atmospheric gases to introduce challenges, such as hypoxia or hypercapnia, significantly impacts the body’s ability to regulate oxygenation and gas transfer. In a diseased state, these changes lead to erratic breathing, apneas and potential long-term effects.
The delivery of controlled gas has many uses in preclinical research: from acute challenges to chronic exposure for an animal model.
CONTINUOUS VENTILATORY PATTERNS
The whole body plethysmography chamber allows for the automated exposure to gas challenges, along with the continuous recording of the subjects ventilatory parameters. During acute exposures, IOX software can control the mixing and delivery of controlled gases with Mass Flow Controllers (MFC). The MFCs can be automated in protocols to vary severity and duration of challenges and returns to normoxia. These challenges can lead to erratic breathing and apneic events, which are recorded and quantified in real time.
In addition to breathing pattern information, plethysmography can be extended with high-fidelity EEG/EMG signals, optogenetics triggering and blood oxygen sensors, which yield further insights into a subject’s ventilatory control during gas challenges.
- Samillan, Victor, et al. “Combination of erythropoietin and sildenafil can effectively attenuate hypoxia-induced pulmonary hypertension in mice.” Pulmonary circulation 3.4 (2013): 898-907.
- Baum, David Marcel, et al. “New Zealand Obese Mice as a Translational Model of Obesity-related Obstructive Sleep Apnea Syndrome.” American journal of respiratory and critical care medicine 198.10 (2018): 1336-1339.
- Voituron, Nicolas, et al. “Early breathing defects after moderate hypoxia or hypercapnia in a mouse model of Rett syndrome.” Respiratory physiology & neurobiology 168.1-2 (2009): 109-118.
- Flor, Karine C., et al. “Short-term sustained hypoxia elevates basal and hypoxia-induced ventilation but not the carotid body chemoreceptor activity in rats.” Frontiers in physiology 9 (2018): 134.
- Bairam, Aida, Delphine Lumbroso, and Vincent Joseph. “Effect of progesterone on respiratory response to moderate hypoxia and apnea frequency in developing rats.” Respiratory physiology & neurobiology 185.3 (2013): 515-525.
INTERVENTION AND MEASUREMENT DEVICE
During gas challenges, subtle changes in the respiratory mechanics can begin to manifest, for instance pulmonary arterial hypertension can cause minor changes in the tissue mechanics of the lungs. The flexiVent uses the forced oscillation technique (FOT) which is sensitive enough to capture structural changes in the lungs. Additionally, certain early life gas exposures can lead to increased airway reactivity, with automated dose responses the flexiVent can assess the airway hyperresponsiveness.
- Kumar, Rahul, et al. “TGF-β activation by bone marrow-derived thrombospondin-1 causes Schistosoma-and hypoxia-induced pulmonary hypertension.” Nature communications 8 (2017): 15494.
- Ramani, Manimaran, et al. “Early exposure to hyperoxia or hypoxia adversely impacts cardiopulmonary development.” American journal of respiratory cell and molecular biology 52.5 (2015): 594-602.