Carotid body chemoreceptors: physiology, pathology, and implications for health and disease

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(3), P. 1177 - 1235

Published: Feb. 11, 2021

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 pH, eliciting reflex ventilatory, cardiovascular, humoral responses to maintain homeostasis. This review examines fundamental biology underlying CB function, its contribution integrated physiological responses, role in maintaining health potentiating disease. Emphasis placed on 1) transduction mechanisms (type I) cells, highlighting played by hypoxic inhibition of O2-dependent K+ channels mitochondrial oxidative metabolism, their modification intracellular molecules other ion channels; 2) synaptic linking type I cells petrosal nerve terminals, focusing proposed transmitters modulatory gases, participation glial regulation chemosensory process; 3) activation, emphasizing that differ dramatically depending nature physiological, pathological, or environmental challenges, interactions with reflexes optimizing oxygen delivery tissues; 4) enhanced discharge autonomic cardiorespiratory pathophysiology obstructive sleep apnea, congestive heart failure, resistant hypertension, metabolic diseases how modulation reactivity disease conditions may attenuate pathophysiology.

Language: Английский

---

Life Ascending: Mechanism and Process in Physiological Adaptation to High-Altitude Hypoxia

Annual Review of Ecology Evolution and Systematics, Journal Year: 2019, Volume and Issue: 50(1), P. 503 - 526

Published: Sept. 3, 2019

To cope with the reduced availability of O2 at high altitude, air-breathing vertebrates have evolved myriad adjustments in cardiorespiratory system to match tissue delivery metabolic demand. We explain how changes interacting steps transport pathway contribute plastic and whole-animal aerobic performance under hypoxia. In native enhancements hypoxia are attributable a combination environmentally induced multiple pathway. Additionally, evidence suggests that many high-altitude natives mechanisms for attenuating maladaptive acclimatization responses hypoxia, resulting counter-gradient patterns altitudinal variation key physiological phenotypes. For traits exhibit counteracting environmental genetic effects, phenotype may be cryptic field conditions can only revealed by rearing representatives high-and low-altitude populations standardized control plasticity.

Language: Английский

---

Opioid-induced respiratory depression in humans: a review of pharmacokinetic–pharmacodynamic modelling of reversal

British Journal of Anaesthesia, Journal Year: 2019, Volume and Issue: 122(6), P. e168 - e179

Published: Feb. 1, 2019

Language: Английский

---

On the significance of estimating cardiorespiratory coupling strength in sports medicine

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 2

Published: Jan. 4, 2023

The estimation of cardiorespiratory coupling (CRC) is attracting interest in sports physiology as an important tool to characterize cardiac neural regulation genuinely driven by respiration. When applied medicine, measurements can provide information on the effects training, pre-competition stress, well cardiovascular adjustments during stressful stimuli. Furthermore, since strongly affected physical activity, study guide application specific training methods optimize between autonomic activity and heart with possible performance. However, a consensus about physiological mechanisms, methodological gold standard quantify coupling, has not been reached yet, thus limiting its experimental settings. This review supports relevance assessing examines mechanisms involved, lists series approaches. strength seems be increased athletes when compared sedentary subjects, addition being associated positive outcomes, such better interaction subsystems cope Moreover, influenced modalities, inspiratory muscle training. impact performance still needs explored through ad hoc exercise tests protocols. In addition, this stresses that several bivariate multivariate have proposed assess opening new possibilities estimating interactions athletes.

Language: Английский

---

Neural Circuitry Underlying Waking Up to Hypercapnia

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: April 26, 2019

Obstructive sleep apnea is a and breathing disorder, in which, patients suffer from cycles of atonia airway dilator muscles during sleep, resulting collapse, followed by brief arousals that help re-establish the patency. These repetitive which can occur hundreds times course night are cause sleep-disruption, turn causes cognitive impairment as well cardiovascular metabolic morbidities. To prevent this potential outcome, it important to target preventing arousal while preserving or augmenting increase respiratory drive reinitiates breathing, but will require understanding neural circuits regulate cortical responses apnea. The parabrachial nucleus (PB) located rostral pons. It receives chemosensory information medullary nuclei sense CO2 (hypercapnia), decrease O2 (hypoxia) mechanosensory inputs negative pressure apneas. PB area also exerts powerful control over respiration, therefore, an excellent candidate for mediating EEG restoration Using various genetic tools, we dissected neuronal sub-types responsible relaying stimulus forebrain circuits. present review focus on circuitries waking-up response hypercapnia.

Language: Английский

---

Translating carotid body function into clinical medicine

The Journal of Physiology, Journal Year: 2017, Volume and Issue: 596(15), P. 3067 - 3077

Published: Nov. 8, 2017

The carotid body (CB) is considered the main O2 chemoreceptor, which contributes to cardiorespiratory homeostasis and ventilatory acclimatization. In clinical medicine, most common pathologies associated with CB are tumours. However, a growing of evidence supports novel idea that an enhanced chemosensory discharge autonomic dysfunction pathological consequences in obstructive sleep apnoea (OSA), hypertension, systolic heart failure (HF) cardiometabolic diseases. Heightened reactivity elicited by oxidative stress has been involved sympathetic hyperactivity, instability, hypertension insulin resistance. ablation, reduces decreases animal models OSA eliminates breathing instability improves survival HF, restores tolerance models. Thus, data obtained from preclinical studies highlight importance progression sympathetic-related diseases, supporting appeasing drive may be useful improving cardiovascular, respiratory endocrine alterations. Accordingly, ablation proposed used as treatment for moderating resistant HF-induced hyperactivity humans. First-in-human have shown overactivity, transiently severe quality life HF patients. would therapy reverse overactivation but caution required before it widely due crucial physiological function played CB. Further assess side-effects ablation.

Language: Английский

---

Multi-Level Regulation of Opioid-Induced Respiratory Depression

Physiology, Journal Year: 2020, Volume and Issue: 35(6), P. 391 - 404

Published: Oct. 14, 2020

Opioids depress minute ventilation primarily by reducing respiratory rate. This results from direct effects on the preBötzinger Complex as well depression of Parabrachial/Kölliker-Fuse Complex, which provides excitatory drive to neurons mediating phase-switch. also awake forebrain and chemodrive.

Language: Английский

---

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers

PLoS ONE, Journal Year: 2017, Volume and Issue: 12(1), P. e0168930 - e0168930

Published: Jan. 3, 2017

A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic (HCVR) in an Asian population. The current evaluated relationship Caucasians and Asians. In addition we assessed whether gender or polymorphisms genes participating control of breathing affect HVR HCVR.A re-breathing system was used to measure HCVR 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 tagged coding variants (PHOX2B, GPR4 TASK2/KCNK5) were analyzed. associations between HVR/HCVR HLA-DQB1*06:02, genetic polymorphisms, using ANOVA frequentist association testing with SNPTEST.HVR are strongly correlated. not. Mean women 0.276±0.168 (liter/minute/%SpO2) compared 0.429±0.266 men, p<0.001 (55.4% higher men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001), SpO2 (98.0±1.3% 96.6±1.7%, EtCO2 (4.65±0.68% 4.82±1.02%, p = 0.025). One hundred two (18.5%) participants HLA-DQB1*06:02. No seen HCVR. Genetic analysis revealed point wise, uncorrected significant TASK2/KCNK5 (rs2815118 rs150380866) HCVR.This is largest date reporting HVR/ first assessing humans HVR/HCVR. data suggest a large effect on response.

Language: Английский

---

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

Neuroscience Bulletin, Journal Year: 2020, Volume and Issue: 36(6), P. 585 - 597

Published: Feb. 24, 2020

Abstract Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, respiration. Dysfunction HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) sudden infant death syndrome. OSA serious breathing disorder the activity during different sleep–wake states. Identifying neural mechanisms by which state-dependent activities are controlled may be helpful providing theoretical basis for effective therapy OSA. However, presynaptic partners governing remain to elucidated. In present study, we used cell-type-specific retrograde tracing system based on modified rabies virus along Cre/loxP gene-expression strategy map whole-brain monosynaptic inputs mice. We identified 53 nuclei targeting from six brain regions: amygdala, hypothalamus, midbrain, pons, medulla, cerebellum. discovered that GABAergic central amygdaloid nucleus, well calretinin parasubthalamic sent projections HMNs. addition, received direct regions respiration, pre-Botzinger complex, parabrachial nucleus solitary tract, hypothalamus. Some engaged regulation (the parafacial zone, ventral sublaterodorsal tegmental dorsal raphe periaqueductal gray, hypothalamus) also provided primary These results contribute further elucidating circuits underlying disorders caused dysfunction

Language: Английский

---

Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 4, 2022

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics WAG/Rij rat, an established rodent model of epilepsy, we demonstrate are highly sensitive arterial carbon dioxide, suggesting pH. Moreover, consistently activated neurons within intralaminar nuclei thalamus, a structure implicated seizure generation. We show thalamus also contains pH-sensitive neurons. Collectively, these observations suggest activates provoke seizures.

Language: Английский

---