Orexin: a Missing Link Between Sleep Disorders and Heart Failure?

Pan, Stephen; Cabral, Carolina S.; Ashley, Euan A.; Pérez, Marco

doi:10.1007/s11897-017-0322-3

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…Orexin B receptor-modulated inputs to neurons residing within the Kölliker-Fuse nucleus deriving from neurons residing within the lateral hypothalamus bear unique functional significance in the maintenance of upper airway tone during sleep (Dutschmann et al, 2007). Pan, Cabral, Ashley, and Perez (2017) hypoglossal pre-inspiratory/inspiratory phase-spanning neurons by neurons residing within the Kölliker-Fuse nucleus (Dutschmann et al, 2007).…”

Section: Parenteral Administration Of Fentanyl Attenuates Discharge Imentioning

confidence: 99%

“…Orexin B receptor‐modulated inputs to neurons residing within the Kölliker–Fuse nucleus deriving from neurons residing within the lateral hypothalamus bear unique functional significance in the maintenance of upper airway tone during sleep (Dutschmann et al., 2007). Pan, Cabral, Ashley, and Perez (2017) have implicated perturbations of orexin signalling and insufficient recruitment of hypoglossal pre‐inspiratory activity by hypoxia and hypercapnia in patients developing obstructive sleep apnoea. Hypoxia paradoxically attenuates the discharge of orexin neurons residing within the lateral hypothalamus in rats (Dergacheva, Yamanaka, Schwartz, Polotsky, & Mendelowitz, 2016), an effect that might presumptively reduce hypothalamic orexinergic drive conveyed to pre‐inspiratory neurons residing within the Kölliker–Fuse nucleus driving hypoglossal pre‐I activity.…”

Section: Propriobulbar Interneuronal Microcircuit Oscillators Conveying Premotoneuronal Pre‐inspiratory Discharge Upon Hypoglossal Motonementioning

confidence: 99%

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Retracted: Control of hypoglossal pre‐inspiratory discharge

Ghali

2020

Experimental Physiology

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The hypoglossal nerve (XII) innervates muscles mediating excursive movements of the tongue. The population discharge of hypoglossalmotoneuronal axons constituting the hypoglossal nerve precedes and extends through the inspiratory epoch. The epoch subtended between the onsets of hypoglossal and phrenic neural discharge constitutes so-called pre-inspiration. Hypoglossal pre-inspiratory neural discharge serendipitously displaces the tongue along a tensor reducing upper airway resistance anticipative of succeeding inspiratory efforts. Hypoglossal motoneurons exhibiting discharge onset during pre-inspiration experience successive hyperpolarization of membrane voltage and attenuation of unitary spiking frequency, although a subset may, paradoxically and state-dependently, exhibit depolarization of membrane voltage and augmentation of neuronal spiking frequency, by dynamic stretch placed upon the alveolar walls and interstitium. Marked static elevation of positive-end expiratory pressure may induce hypoglossal bursting decoupled from phasic rhythmic phrenic discharge. Augmentation of the amplitude and/or duration of hypoglossal inspiratory discharge during successive pre-inspiratory and inspiratory epochs by inhalation of a hypoxic and/or hypercapnic gas mixture remains restrained in the presence of intact vagal inputs and is potentiated by interruptions of vagal continuity. Unravelling the mechanisms underlying the genesis of pre-inspiratory activity will inform our understanding of respiratory rhythm generation and pattern shaping. In the present work, I seek to explore the mechanisms underlying modulation of hypoglossal pre-inspiratory discharge by hypercapnia, hypoxia and static and dynamic lung stretch placed upon hypoglossal pre-inspiratory activity, the mechanisms underlying the generation of hypoglossal pre-inspiratory activity, and the extent of microanatomical and functional overlap between propriobulbar interneuronal microcircuits generating hypoglossal pre-inspiratory activity and propriobulbar interneuronal microcircuit oscillators generating pre-inspiratory activity inaugurally inducing respiratory rhythmic activity and thus use experimental data from previous work and that developed by other investigators to explore the modulatory role of lung vagal afferents and intra-neuraxial and carotid body chemoreceptors upon hypoglossal pre-inspiratory activity.

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Section: Parenteral Administration Of Fentanyl Attenuates Discharge Imentioning

confidence: 99%

Section: Propriobulbar Interneuronal Microcircuit Oscillators Conveying Premotoneuronal Pre‐inspiratory Discharge Upon Hypoglossal Motonementioning

confidence: 99%

Retracted: Control of hypoglossal pre‐inspiratory discharge

Ghali

2020

Experimental Physiology

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“…with acute coronary syndrome or congestive heart failure) were excluded from the relevant trials (http://www.acc.org/latest-in-cardiology/articles/2015/06/16/08/40/new-insomnia-drugs-in-the-context-of-cardiovascular-disease). Therefore, and based on the findings from our study and from others [67], the use of orexin antagonists may warrant further assessment and careful monitoring for CVD adverse effects, particularly in heart failure patients [69].…”

Section: Discussionmentioning

confidence: 81%

Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection

et al. 2018

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Orexins/hypocretins exert cardiovascular effects which are centrally mediated. In the present study, we tested whether orexins and their receptors may also act in an autocrine/paracrine manner in the heart exerting direct effects. Quantitative reverse transcription-PCR (RT-PCR), immunohistochemical and Western blot analyses revealed that the rat heart expresses orexins and orexin receptors (OXR). In isolated rat cardiomyocytes, only orexin-B (OR-B) caused an increase in contractile shortening, independent of diastolic or systolic calcium levels. A specific orexin receptor-2 (OX2R) agonist ([Ala11, d-Leu15]-Orexin B) exerted similar effects as OR-B, whereas a specific orexin receptor-1 (OX1R) antagonist (SB-408124) did not alter the responsiveness of OR-B. Treatment of the same model with OR-B resulted in a dose-dependent increase in myosin light chain and troponin-I (TnI) phosphorylation. Following ischaemia/reperfusion in the isolated Langendorff perfused rat heart model, OR-B, but not OR-A, exerts a cardioprotective effect; mirrored in an in vivo model as well. Unlike OR-A, OR-B was also able to induce extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2) and Akt phosphorylation in rat myocardial tissue and ERK1/2 phosphorylation in human heart samples. These findings were further corroborated in an in vivo rat model. In human subjects with heart failure, there is a significant negative correlation between the expression of OX2R and the severity of the disease clinical symptoms, as assessed by the New York Heart Association (NYHA) functional classification. Collectively, we provide evidence of a distinct orexin system in the heart that exerts a cardioprotective role via an OR-B/OX2R pathway.

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“…The relationship between HF and sleep is, again, likely bi-directional. Sleep disturbance is associated with several cardiovascular disease risk factors, and cardiovascular disease, in addition to higher sympathetic activity [153][154][155]. With this considered, sleep disturbance may lie along the causal pathway for forms of HF, or potentially exacerbate the condition.…”

Section: Heart Failurementioning

confidence: 99%

Sleep Disturbance, Sleep Disorders and Co-Morbidities in the Care of the Older Person

Carthy

2021

Medical Sciences

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Sleep complaints can be both common and complex in the older patient. Their consideration is an important aspect of holistic care, and may have an impact on quality of life, mortality, falls and disease risk. Sleep assessment should form part of the comprehensive geriatric assessment. If sleep disturbance is brought to light, consideration of sleep disorders, co-morbidity and medication management should form part of a multifaceted approach. Appreciation of the bi-directional relationship and complex interplay between co-morbidity and sleep in older patients is an important element of patient care. This article provides a brief overview of sleep disturbance and sleep disorders in older patients, in addition to their association with specific co-morbidities including depression, heart failure, respiratory disorders, gastro-oesophageal reflux disease, nocturia, pain, Parkinson’s disease, dementia, polypharmacy and falls. A potential systematic multidomain approach to assessment and management is outlined, with an emphasis on non-pharmacological treatment where possible.

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Orexin: a Missing Link Between Sleep Disorders and Heart Failure?

Cited by 8 publications

References 35 publications

Retracted: Control of hypoglossal pre‐inspiratory discharge

Retracted: Control of hypoglossal pre‐inspiratory discharge

Functional cardiac orexin receptors: role of orexin-B/orexin 2 receptor in myocardial protection

Sleep Disturbance, Sleep Disorders and Co-Morbidities in the Care of the Older Person

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