Human Ventilatory Response Research Articles

Acute effects of increased gut microbial fermentation on the hypoxic ventilatory response in humans

What is the central question of this study? Is there a link between gut microbial fermentation and ventilatory responsiveness to hypoxia in humans? What is the main finding and its importance? Increased gut microbial fermentation is associated with augmented ventilatory (but not haemodynamic) responses to transient hypoxia. These findings imply a capacity for gut microbiota to modulate the peripheral chemoreflex response to hypoxia in humans. Recent animal data indicate the presence of a bidirectional link between gut microbial activity and respiratory control. Nevertheless, the presence of a similar association between gut microbiota and peripheral chemoreceptor responsiveness to hypoxia in humans has not been reported to date. Therefore, we performed a within subject, placebo-controlled study in a group of 16 healthy individuals (eight men; mean±SD age 25.9±5.2years). Participants underwent two tests (in a random order), receiving lactulose, which stimulates gut fermentation, or placebo. Ventilatory and haemodynamic responses to transient hypoxia were evaluated before and 2h after the test meal. The magnitude of these responses was related to the net hydrogen content in the exhaled air, reflecting gut fermentation intensity. A lactulose meal, compared to placebo, caused an increase in the minute ventilation (Hyp-VI; l/min/ ) and breathing rate (Hyp-BR; breaths/min/ ) responses to hypoxia (for Hyp-VI, mean±SD -0.03±0.059 in placebo test vs. 0.05±0.116 in lactulose test, P=0.03; for Hyp-BR, -0.015±0.046 vs. 0.034±0.054, P=0.01). The magnitude of these responses was positively correlated with the lactulose-induced hydrogen excretion (for Hyp-VI, r=0.62, P=0.01; for Hyp-BR, r=0.73, P=0.001). Changes in the resting parameters during normoxia did not differ significantly between the tests. Our results demonstrate that the increased gut microbial fermentation is associated with augmented ventilatory (but not haemodynamic) responses to the transient hypoxia, which implies a capacity for gut microbiota to modulate the peripheral chemoreflex in humans.

The role of muscle mechano and metaboreflexes in the control of ventilation: breathless with (over) excitement?

Mechanically and metabolically sensitive thin fibre (group III and IV) muscle afferents are activated during exercise, causing reflex cardiovascular responses that are essential to normal cardiovascular control. Impaired exercise performance in some disease states can be linked to abnormal muscle mechanoreflex and muscle metaboreflex activity. A role for this same afferent feedback in contributing to the hyperpnoea of exercise and the dyspnoea experienced by some patient groups on exercise has recently received increased attention. Evidence is summarised here that supports a role for muscle mechanoreflex and muscle metaboreflex involvement in the human ventilatory response to exercise and also their synergistic interaction with the central chemoreflex during muscular activity. The effects of local muscle training induced attenuation of the human muscle metaboreflex on this synergistic interaction and associated decrease in ventilation is discussed.

Sensitivity of the human ventilatory response to muscle metaboreflex activation during concurrent mild hypercapnia.

What is the central question of this study? What is the relationship between the level of systemic hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation? What is the main finding and its importance? When a standardized activation of the muscle metaboreflex was combined with exposure to increasing levels of hypercapnia, the hyperpnoea this caused increased linearly. The concept of a synergistic interaction between the muscle metaboreflex and the central chemoreflex in humans is supported by this finding. Ventilation increases during muscle metaboreflex activation when postexercise circulatory occlusion (PECO) traps metabolites in resting human muscle, but only in conditions of concurrent systemic hypercapnia. We hypothesize that a linear relationship exists between the level of hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation. Fifteen male subjects performed four trials, in which the end-tidal partial pressure of carbon dioxide ( ) was elevated by 1, 3, 7 or 10mmHg above resting values using a dynamic end-tidal forcing system. In each trial, subjects were seated in an isometric dynamometer designed to measure ankle plantar flexor force. Rest for 2 min in room air was followed by 15min of exposure to one of the four levels ofhypercapnia, at which 5min further rest was followed by 2 min of sustained isometric calf muscle contraction at 50% of predetermined maximal voluntary strength. Immediately before cessation of exercise, a cuff around the upper leg was inflated to a suprasystolic pressure to cause PECO for 3min, before its deflation and a further 5min of rest, concluding exposure to hypercapnia. The PECO consistently elevated mean arterial blood pressure by ∼10mmHg in all trials, indicating similar levels of metaboreflex activation. Increased ventilation during PECO was related to as described by the following linear regression equation: Change in minute ventilation (lmin-1 )=0.85× (mmHg)+0.80 (lmin-1 ). This finding supports our hypothesis and furthers the idea of a synergistic interaction between muscle metaboreflex activation and central chemoreflex stimulation.

The human ventilatory response to stress: rate or depth?

Many stressors cause an increase in ventilation in humans. This is predominantly reported as an increase in minute ventilation (V̇E). But, the same V̇E can be achieved by a wide variety of changes in the depth (tidal volume, VT ) and number of breaths (respiratory frequency, ƒR ). This review investigates the impact of stressors including: cold, heat, hypoxia, pain and panic on the contributions of ƒR and VT to V̇E to see if they differ with different stressors. Where possible we also consider the potential mechanisms that underpin the responses identified, and propose mechanisms by which differences in ƒR and VT are mediated. Our aim being to consider if there is an overall differential control of ƒR and VT that applies in a wide range of conditions. We consider moderating factors, including exercise, sex, intensity and duration of stimuli. For the stressors reviewed, as the stress becomes extreme V̇E generally becomes increased more by ƒR than VT . We also present some tentative evidence that the pattern of ƒR and VT could provide some useful diagnostic information for a variety of clinical conditions. In The Physiological Society's year of 'Making Sense of Stress', this review has wide-ranging implications that are not limited to one discipline, but are integrative and relevant for physiology, psychophysiology, neuroscience and pathophysiology.

Dynamic ventilatory responses of females and males to acute isocapnic and poikilocapnic hypoxia

The human ventilatory response during acute hypoxia appears to be biphasic (growth and decay), but the effect of sex on the size and timing of this response is not known. We studied the effects of 15min of poikilocapnic and isocapnic hypoxia (FiO2≈0.10) on ventilation (V˙i) in 14 healthy female and 13 healthy male subjects. Parameters (amplitudes, time delays, time constants) describing individual V˙i responses were estimated using a biexponential function. There were no significant effects of sex on any of these parameters. CO2 regulation significantly altered the amplitudes of growth and decay phases and the onset of the latter phase in females and males. These human data suggest that sex does not affect the biphasic response of ventilation during hypoxia. However, additional evidence in this study suggests that sex influences the breathing frequency response during hypoxia and that this effect depends on the control of CO2.

Experimental and theoretical studies of human hypercapnic ventilatory response with the use of mathematical modeling of gas exchange

A mathematical model of the biotechnical system integrating the human cardiorespiratory system with a hard- and software suite (HSS) was designed to investigate breathing control. The model describes the dynamics of carbon dioxide and oxygen in three biotechnical system compartments in the course of rebreathing tests. The tests do not require tanks with compressed gas and, hence, can be performed in space flights. The results of simulated modeling of the ventilation response in two breath tests, i.e., to hypercapnia due to rebreathing hyperoxic gas mixture (HGM) and to hypercapnia combined with hypoxia due to air rebreathing are presented. The model validity was verified by comparison between the modeling and experimental data. The mathematical model made it evident that CO2 partial pressures in tissues, the lungs, and the breathing circuit equalize very fast when the initial carbon dioxide concentration in the respiration circuit is equal to the end-tidal CO2 concentration in humans at rest.

Ventilatory responses to muscle metaboreflex activation in chronic obstructive pulmonary disease.

Recent evidence indicates a role for group III/IV muscle afferents in reflex control of the human ventilatory response to exercise. Dyspnoea in chronic obstructive pulmonary disease (COPD) may be linked to this reflex response. This study shows that activation of the muscle metaboreflex causes a ventilatory response in COPD patients but not in healthy controls. This indicates abnormal involvement of muscle afferents in the control of ventilation in COPD which may be a contributing factor to exercise dyspnoea. Blockade of thin fibre muscle afferent feedback during dynamic exercise reduces exercise hyperpnoea in health and chronic obstructive pulmonary disease (COPD). Therefore, we hypothesised that activation of the muscle metaboreflex at rest would cause hyperpnoea. We evaluated the effect of muscle metaboreflex activation on ventilation, in resting COPD patients and healthy participants. Following a bout of rhythmic hand grip exercise, post exercise circulatory occlusion (PECO) was applied to the resting forearm to sustain activation of the muscle metaboreflex, in 18 COPD patients (FEV1 /FVC ratio <70%), 9 also classified as chronically hypercapnic, and 9 age- and gender-matched controls. The cardiovascular response to exercise and the sustained blood pressure elevation during PECO was similar in patients and controls. During exercise ventilation increased by 6.64±0.84 in controls and significantly (P<0.05) more, 8.38±0.81lmin-1 , in patients. During PECO it fell to baseline levels in controls but remained significantly (P<0.05) elevated by 2.78±0.51lmin-1 in patients until release of circulatory occlusion, with no significant difference in responses between patient groups. Muscle metaboreflex activation causes increased ventilation in COPD patients but not in healthy participants. Chronic hypercapnia in COPD patients does not exaggerate this response. The muscle metaboreflex appears to be abnormally involved in the control of ventilation in COPD and may be a contributing factor to exercise dyspnoea.

Thermoregulatory and Ventilatory Responses in Humans with a Patent Foramen Ovale During Passive Cooling While Immersed in 20 °C Water

Approximately 35% of the general healthy population has a patent foramen ovale (PFO). People without a PFO (PFO−) have a lower esophageal temperature (Tesoph) under resting conditions and during exercise. Additionally, while breathing super cooled (−2.0 °C) air at the end of a 10‐minute exercise bout (2:30 stages at 25, 50, 75 and 90% of VO2MAX), PFO− subjects did not increase Tesoph as much as subjects with a PFO (PFO+). These data suggest blunted respiratory system cooling in PFO+ subjects. Taken together, these data suggest differences between PFO− and PFO+ subjects in thermoregulatory and ventilatory responses at rest and during exercise. However, to our knowledge it has not been prospectively determined if a PFO has any role on thermoregulatory and ventilatory responses to passive cooling.Fourteen males matched for height, weight and age participated in this study (9 PFO−; age: 26 ± 6 yrs, height: 180.1 ± 7.2 cm, weight: 83.3 ± 12.3 kg, BSA: 2.0 ± 0.2 m2; 5 PFO+; age: 28 ± 6 yrs, height: 175.8 ± 7.3 cm, weight: 77.7 ± 6.0 kg, BSA: 2.0 ± 0.1 m2). Subjects came to the lab at the same time each morning and laid in a reclined position, immersed to the nipple line in a water bath (19.6 ± 0.7 °C) until 1) 60 minutes elapsed, 2) Tesoph decreased to 35.5 °C, 3) sustained shivering occurred (oxygen uptake [VO2] &gt; 25% of resting values for 5 consecutive minutes), or 4) subjects asked to get out of the water.We measured Tesoph, VO2 and minute ventilation (VE) every 5 minutes. At rest before immersion PFO− subjects had a lower Tesoph than PFO+ subjects (PFO−: 36.5 ± 0.2, PFO+: 36.8 ± 0.2, p = .04). At the end of immersion PFO− subjects also had a lower Tesoph than PFO+ subjects (PFO− : 36.0 ± 0.4, PFO+: 36.5 ± 0.3, p = .04). There were no differences in VO2 or VE at any time point. Furthermore, after the initial increase in Tesoph upon immersion, PFO− subjects decreased Tesoph throughout the remainder of the trial; while PFO+ subjects drop in Tesoph plateaued after 50 minutes of immersion. These data suggest that PFO− subjects are unable to retain heat as effectively as PFO+ subjects during passive cooling. This may be due to the possibility that PFO− subjects have greater respiratory system heat loss than PFO+ subjects.Support or Funding Information2015 Eugene and Clarissa Evonuk Memorial Graduate Fellowship

Revisiting dysanapsis: sex-based differences in airways and the mechanics of breathing during exercise.

What is the topic of this review? This review focuses on sex-based differences in the anatomy of the respiratory system, which manifest in mechanical ventilatory constraints and potentially alter the integrative response to exercise. What advances does it highlight? Recent evidence indicates that women have smaller conducting airways than men, even when matched for lung size. Consequently, women are more likely to experience mechanical ventilatory constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women have a higher work and oxygen cost of breathing, both of which may lead to differences in the whole-body integrative response to dynamic exercise. Our understanding of the human ventilatory response to exercise is largely based on a historical body of literature focused primarily on male rather than female research subjects. In recent years, important sex-based differences in the anatomy of the human respiratory system have been identified; for a given lung size, women appear to have smaller-diameter conducting airways than men. The presence of such inherent differences in the tracheobronchial tree greatly affects the mechanics of airflow generation, especially during conditions of high ventilation rates, such as exercise. Data from a growing number of studies suggest that women may be more susceptible to respiratory system limitations during exercise than their male counterparts. Specifically, women are more likely to experience expiratory flow limitation and exercise-induced arterial hypoxaemia and have a higher metabolic cost of breathing for a given ventilation. Collectively, the available evidence suggests that sex differences in the ventilatory response to exercise are present and may have important ramifications for the integrated response to exercise; however, several fundamental questions remain unanswered.

Measuring the human ventilatory and cerebral blood flow response to CO2: a technical consideration for the end-tidal-to-arterial gas gradient.

Our aim was to quantify the end-tidal-to-arterial gas gradients for O2 (PET-PaO2) and CO2 (Pa-PETCO2) during a CO2 reactivity test to determine their influence on the cerebrovascular (CVR) and ventilatory (HCVR) response in subjects with (PFO+, n = 8) and without (PFO-, n = 7) a patent foramen ovale (PFO). We hypothesized that 1) the Pa-PETCO2 would be greater in hypoxia compared with normoxia, 2) the Pa-PETCO2 would be similar, whereas the PET-PaO2 gradient would be greater in those with a PFO, 3) the HCVR and CVR would be underestimated when plotted against PETCO2 compared with PaCO2, and 4) previously derived prediction algorithms will accurately target PaCO2. PETCO2 was controlled by dynamic end-tidal forcing in steady-state steps of -8, -4, 0, +4, and +8 mmHg from baseline in normoxia and hypoxia. Minute ventilation (V̇E), internal carotid artery blood flow (Q̇ICA), middle cerebral artery blood velocity (MCAv), and temperature corrected end-tidal and arterial blood gases were measured throughout experimentation. HCVR and CVR were calculated using linear regression analysis by indexing V̇E and relative changes in Q̇ICA, and MCAv against PETCO2, predicted PaCO2, and measured PaCO2. The Pa-PETCO2 was similar between hypoxia and normoxia and PFO+ and PFO-. The PET-PaO2 was greater in PFO+ by 2.1 mmHg during normoxia (P = 0.003). HCVR and CVR plotted against PETCO2 underestimated HCVR and CVR indexed against PaCO2 in normoxia and hypoxia. Our PaCO2 prediction equation modestly improved estimates of HCVR and CVR. In summary, care must be taken when indexing reactivity measures to PETCO2 compared with PaCO2.

Aminophylline increases respiratory muscle activity during hypercapnia in humans

BackgroundTheophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. Study designWe performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. ResultsBefore aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. ConclusionAminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.

Central chemoreflex ventilatory responses in humans following passive heat acclimation

Since there is temperature dependence of pulmonary ventilation (V˙(E)) in response to the normal modulators (i.e. [Formula: see text] , [Formula: see text] ), it was asked in this study if passive heat acclimation (HA) modifies the human central chemoreflex ventilatory response to CO(2). Nine males performed normothermic- and hyperthermic modified Read re-breathing tests before and after HA. Heat acclimation consisted of 2hday(-1) exposures to 50°C and 20% RH for 10 consecutive days and each exposure elevated rectal temperature to between 38.5 and 39.0°C. Ventilatory recruitment thresholds (VRTs) and central chemosensitivity were assessed before and after HA during normothermia with an oesophageal temperature (T(es)) of ∼37°C and in hyperthermia when T(es) was 38.5-39.0°C. Results showed VRT and central chemosensitivities were unaltered by HA (p≥0.375) and hyperthermia increased pre- (p=0.010) but not post-acclimation (p=0.332) central chemosensitivity. Additionally, during hyperthermia V˙(E) became progressively greater (p=0.027) relative to corresponding normothermic values in the re-breathing tests. In conclusion, the ventilatory response to hyperoxic CO(2) was unaltered by heat Acclimation State.

The Human Carotid Body

Hypoxia is a common cause of adverse events in the postoperative period, where respiratory depression due to residual effects of drugs used in anesthesia is an important underlying factor. General anesthetics and neuromuscular blocking agents reduce the human ventilatory response to hypoxia. Although the carotid body (CB) is the major oxygen sensor in humans, critical oxygen sensing and signaling pathways have been investigated only in animals so far. Thus, the aim of this study was to characterize the expression of key genes and localization of their products involved in the human oxygen sensing and signaling pathways with a focus on receptor systems and ion channels of relevance in anesthesia. Six CBs were removed unilaterally from patients undergoing radical neck dissection. The gene expression and cell-specific protein localization in the CBs were investigated with DNA microarrays, real-time polymerase chain reaction, and immunohistochemistry. We found gene expression of the oxygen-sensing pathway, heme oxygenase 2, and the K channels TASK (TWIK-related acid sensitive K channel)-1 and BK (large-conductance potassium channel). In addition, we show the expression of critical receptor subunits such as γ-aminobutyric acid A (α2, β3, and γ2), nicotinic acetylcholine receptors (α3, α7, and β2), purinoceptors (A2A and P2X2), and the dopamine D2 receptor. In unique samples of the human CB, we here demonstrate presence of critical proteins in the oxygen-sensing and signaling cascade. Our findings demonstrate similarities to, but also important differences from, established animal models. In addition, our work establishes an essential platform for studying the interaction between anesthetic drugs and human CB chemoreception.

Short- and Long-Term Modulation of the Exercise Ventilatory Response

The importance of adaptive control strategies (modulation and plasticity) in the control of breathing during exercise has become recognized only in recent years. In this review, we discuss new evidence for modulation of the exercise ventilatory response in humans, specifically, short- and long-term modulation. Short-term modulation is proposed to be an important regulatory mechanism that helps maintain blood gas homeostasis during exercise.

Effects of Exposure to Intermittent Hypoxia on Oxidative Stress and Acute Hypoxic Ventilatory Response in Humans

Periodic occlusion of the upper airway in patients with obstructive sleep apnea leads to chronic intermittent hypoxia, which increases the acute hypoxic ventilatory response (AHVR). Animal studies suggest that oxidative stress may modulate AHVR by increasing carotid body sensitivity to hypoxia. This has not been shown in humans. To determine whether 4 days of exposure to chronic intermittent hypoxia increases AHVR and oxidative stress and to determine the strength of the association between oxidative stress and AHVR. After two normoxic control days (Day -4 and Day 0), 10 young healthy men were exposed awake to 4 days (Days 1-4) of intermittent hypoxia for 6 hours per day. AHVR, assessed using an isocapnic hypoxia protocol, was determined as the slope of the linear regression between ventilation and oxygen desaturation. Oxidative stress was evaluated by measuring plasma DNA, lipid and protein oxidation, uric acid and antioxidant status by measuring alpha-tocopherol, total vitamin C, and antioxidant enzymatic activities. Between baseline and Day 4, there were significant increases in AHVR, DNA oxidation, uric acid, and vitamin C, whereas antioxidant enzymatic activities and alpha-tocopherol were unchanged. There were strong correlations between the changes in AHVR and DNA oxidation (r = 0.88; P = 0.002). Chronic intermittent hypoxia increases oxidative stress by increasing production of reactive oxygen species without a compensatory increase in antioxidant activity. This human study shows that reactive oxygen species overproduction modulates increased AHVR. These mechanisms may be responsible for increased AHVR in patients with obstructive sleep apnea.

Aminophylline increases parasternal intercostal muscle activity during hypoxia in humans

To clarify the mechanism of action of aminophylline on the hypoxic ventilatory response in humans, we analyzed the effects of aminophylline on respiratory neural output. To evaluate the respiratory neural output, we analyzed the electromyogram (EMG) of the parasternal intercostal muscle, one of the major inspiratory muscles, in eight healthy subjects. Both before and during aminophylline administration, measurements of ventilatory parameters with EMG recordings were conducted in room air, mild hypoxia (F(I)(o)(2) 0.15), and severe hypoxia (F(I)(o)(2) 0.11). Before administering aminophylline, hypoxic stimulation elicited ventilatory augmentation in a hypoxia-intensity dependent manner. Administration of aminophylline caused significant increases in ventilation (V (I)), tidal volume (V(T)), respiratory frequency (f(R)), and the respiration-related phasic moving averaged EMG amplitude (tidal EMG), at corresponding levels of hypoxia compared to before aminophylline. Augmentation patterns of hypoxia-induced increases in V(T) and tidal EMG showed close similarity. These results indicate that augmentation of hypoxic ventilatory response by aminophylline is mainly mediated by an increase in the respiratory neural drive in healthy humans.

Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K(+)-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+) channels.

The effects of hypo‐ and hyperglycaemia on the hypoxic ventilatory response in humans

Animal and tissue studies have indicated that the carotid bodies are sensitive to glucose concentrations within the physiological range. This glucose sensitivity may modulate the ventilatory response to hypoxia, with hyperglycaemia suppressing the hypoxic response and hypoglycaemia stimulating it. This study was designed to determine whether hypo- and hyperglycaemia modulate the hypoxic ventilatory response in humans. In 11 normal research participants, glucose levels were clamped at 2.8 and 11.2 mmol l(-1) for 30 min. At the start and end of each clamp, blood was drawn for hormone measurement and the isocapnic hypoxic ventilatory response was measured. Because generation of reactive oxygen species may be a common pathway for the interaction between glucose and oxygen levels, the experiments were repeated with and without pretreatment for 1 week with vitamins C and E. Hypoglycaemia caused an increase in the counter-regulatory hormones, a 54% increase in isocapnic ventilation, and a 108% increase in the hypoxic ventilatory response. By contrast, hyperglycaemia resulted in small but significant increases in both ventilation and the hypoxic ventilatory response. Antioxidant vitamin pretreatment altered neither response. In conclusion, the stimulant effect of hypoglycaemia on the hypoxic ventilatory response is consistent with a direct effect on the carotid body, but an indirect effect through the activation of the counter-regulatory response cannot be excluded. The mechanisms behind the mild stimulating effect of hyperglycaemia remain to be elucidated.

Physiological responses to hypoglycaemia – not all ‘just in the head'

Physiological responses to hypoglycaemia – not all ‘just in the head'

Volatile anesthetics and the hypoxic ventilatory response: effects, clinical implications, and future research

This review discusses the implications of some early findings concerning the effect of volatile anesthetic agents on the human ventilatory response to hypoxia. The impact of different methods of study are discussed, as is the relevance and limitations of animal studies. The review speculates that a relatively simple observation from human study can lead to important questions, answerable using newer technologies such as functional magnetic resonance imaging, intracellular calcium imaging and single-cell/single-channel voltage clamping.