title: Quantifying hypoxia-induced chemoreceptor sensitivity in the awake rodent.
abstract: We evaluated several methods for characterizing hypoxic chemosensitivity in the conscious rat. Adult Sprague-Dawley rats (n = 30) were exposed to normobaric hypoxia [inspired oxygen fraction (Fio2) 0.15, 0.12, and 0.09]. We measured ventilation (V̇e; barometric plethysmography), arterial oxygen saturation (SpO2; pulse oximeter), and oxygen consumption and carbon dioxide production (V̇o2 and V̇co2; analysis of expired air). Linear regression analysis was used to define stimulus-response relationships. Testing was performed on 2 days to assess day-to-day reproducibility. Exposure to graded, steady-state hypoxia caused progressive reductions in SpO2 that were, for any given Fio2, quite variable (SpO2 range, 20-30%) among individuals. Hypoxia produced progressive increases in V̇e caused by increases in both tidal volume (VT) and breathing frequency. Hypoxia also increased the VT:inspiratory time (Ti) ratio, an indicator of central respiratory "drive." Hypoxia caused consistent, progressive declines in V̇o2, V̇co2, and core temperature (>20% at the lowest SpO2). We propose that optimal quantification of carotid chemoreceptor hypoxic sensitivity in the unanesthetized rodent should employ SpO2 [a surrogate for arterial Po2 (PaO2 )] as the stimulus variable and the ventilatory equivalent for V̇co2 (V̇e/V̇co2) and/or mean inspiratory flow rate (VT/Ti) normalized for V̇co2 as the response variables. Both metrics take into account not only the important influence of a falling metabolic rate, but also SpO2, which represents the hypoxic stimulus at the carotid body. Because of the somewhat curvilinear nature of these responses, exposure to multiple levels of graded hypoxia provides the most complete characterization of hypoxic chemosensitivity.
authors: Department of Orthopedics and Rehabilitation and the John Rankin Laboratory of Pulmonary Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; morgan@ortho.wisc.edu.
authors: Barbara J
authors: BJ
authors: Morgan
authors: Department of Orthopedics and Rehabilitation and the John Rankin Laboratory of Pulmonary Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin;
authors: Russell
authors: R
authors: Adrian
authors: Department of Pediatrics and the John Rankin Laboratory of Pulmonary Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin;
authors: Melissa L
authors: ML
authors: Bates
authors: Pharmacy Practice Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin.
authors: John M
authors: JM
authors: Dopp
authors: Department of Population Health Sciences and the John Rankin Laboratory of Pulmonary Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin; and.
authors: Jerome A
authors: JA
authors: Dempsey
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D010991:Plethysmography; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012119:Respiration; D056152:Respiratory Rate / Q000502:physiology; D013990:Tidal Volume / Q000502:physiology
keywords: chemoreflex; hypoxic ventilatory response; metabolic rate