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.

Oxidative stress augments chemoreflex sensitivity in rats exposed to chronic intermittent hypoxia

“…In addition, ventilatory equivalents for both V̇O 2 and V̇CO 2 and mean inspiratory flow rate normalized for V̇CO 2 (VT/T i /V̇CO 2 ), two indicators of chemoreflex response, were substantially increased during acute exposure to graded hypoxia (p<0.001 for both; data not shown). These cardiorespiratory responses to acute hypoxia are consistent with those reported in previous publications (Morgan et al, 2014; Morgan et al, 2016). …”

“…As we have reported previously (Morgan et al, 2014), there was considerable inter-subject variation in SpO 2 at each level of hypoxic inspirate (range, 57–80% at FIO 2 of 0.09). Acute exposure to graded, steady-state hypoxia caused progressive increases in V̇ E , VT, and f B (p<0.001 for each) and concomitant progressive decreases in metabolic rate (p<0.001 for both V̇O 2 and V̇CO 2 ) (Figure 1).…”

Humans In Hypoxia: A Conspiracy Of Maladaptation?!

“…Upon exposure to acute hypoxia, the laboratory rodent, unlike the adult human but like other small mammals, quickly lowers metabolic rate and core body temperature, thereby reducing much of the associated high costs of cardioventilatory responses to hypoxia without sacrificing blood gas transport (73,77). Paradoxically, one important mediator of this hypoxic-induced hypometabolism in small mammals may be found in a carotid chemoreceptor-induced reduction in sympathetic outflow to brown adipose tissue (75).…”

Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability <em>In Vivo</em>

“…Figure 1 shows the multi-parameter monitoring, including ECoG and vital constants, of the animal's physiological state before ( Figure 1A) and after ( Figure 1B) induction of the isoelectric state. During the control sessions, the physiological parameters were similar to those measured in healthy and awake animals [32][33][34][35] and remained unaffected after induction of the isoelectric state, except for the heart rate that was slightly slowed down (Figure 1). This is an important point since hypoxia 39 or hypercapnia 40 can markedly alter neuronal excitability and thus can introduce a serious bias in a study exploring a brain statedependent modulation of neuronal integrative properties.…”