Oxygen deficiency or hypoxia can contribute to the development or exacerbation of many disorders including strokes or chronic lung diseases. The first defense against hypoxia is the hypoxic ventilatory response (HVR). These cardiorespiratory reflexes, like hyperventilation or sympathetic activation, increase gas exchange in the lungs and oxygen delivery to vital organs. Genetically modified mice help researchers identify the processes involved in a hypoxic response, however in order to properly study these responses, reliable methodologies are necessary to understand changes in breathing patterns. Whole-body plethysmography is one important technique for in vivo assessment.
The most important chemoreceptor in mammals is the carotid body (CB), and this organ contains O2-sensing neuron-like glomus cells among others. Dr. Ortega-Sáenz’ group studied the hypoxic response in the CB by using whole-body plethysmography combined with gas mixing. They generated normoxic, hypoxic, or hypercapnic conditions to compare ventilatory responses. The Ndufs2 gene was deleted in a genetically modified mouse (TH-NDUFS2 mouse) which removed the responsiveness to hypoxia while leaving the response to hypercapnia. In their studies, the wild-type mouse responded to hypoxia and hypercapnia with an increase in breathing frequency, while the TH-NDUFS2 mouse only mediated its response in hypercapnic conditions. Although many respiratory variables can be recorded, this group chose breathing frequency as the most reliable and informative parameter and concluded that normal O2-sensing in CB glomus cells is necessary for a normal HVR.
Plethysmography is a standard method for studying pulmonary function in conscious, spontaneously breathing laboratory subjects. The barometric plethysmography technique measures flow and pressure changes that occur while the subject is breathing, before and after exposure to a drug or other challenges. It is easily adapted to various subject sizes and species, and is often used for longitudinal studies where the subjects are studied for multiple hours on successive experiment days.
Ortega-Sáenz, Patricia, et al. "Testing Acute Oxygen Sensing in Genetically Modified Mice: Plethysmography and Amperometry." Hypoxia. Humana Press, New York, NY, 2018. 139-153.
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