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Nature Nov 2023Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders. The Bezold-Jarisch reflex (BJR), first described...
Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders. The Bezold-Jarisch reflex (BJR), first described in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses-hypotension, bradycardia and suppressed respiration-and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push-pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels.
Topics: Humans; Area Postrema; Bradycardia; Cardiac Output, Low; Echocardiography; Heart; Heart Rate; Hypotension; Laser-Doppler Flowmetry; Nerve Net; Reflex; Sensory Receptor Cells; Single-Cell Gene Expression Analysis; Syncope; Vagus Nerve
PubMed: 37914931
DOI: 10.1038/s41586-023-06680-7 -
Current Opinion in Neurology Feb 2024This review considers recent observations on vestibular syncope in terms of clinical features, laboratory findings, and potential mechanisms. (Review)
Review
PURPOSE OF REVIEW
This review considers recent observations on vestibular syncope in terms of clinical features, laboratory findings, and potential mechanisms.
RECENT FINDINGS
Vestibular syncope, potentially associated with severe fall-related injuries, may develop multiple times in about one-third of patients. Meniere's disease and benign paroxysmal positional vertigo are the most common causes of vestibular syncope, but the underlying disorders remain elusive in 62% of cases with vestibular syncope. The postictal orthostatic blood pressure test exhibits a lower diagnostic yield. Vestibular function tests, such as cervical vestibular-evoked myogenic potentials and video head impulse tests, can reveal one or more abnormal findings, suggesting compensated or ongoing minor vestibular dysfunctions. The pathomechanism of syncope is assumed to be the erroneous interaction between the vestibulo-sympathetic reflex and the baroreflex that have different operating mechanisms and action latencies. The central vestibular system, which estimates gravity orientation and inertia motion may also play an important role in abnormal vestibulo-sympathetic reflex.
SUMMARY
Vestibular disorders elicit erroneous cardiovascular responses by providing false vestibular information. The results include vertigo-induced hypertension or hypotension, which can ultimately lead to syncope in susceptible patients.
Topics: Humans; Syncope; Vestibule, Labyrinth; Benign Paroxysmal Positional Vertigo; Hypertension
PubMed: 38193502
DOI: 10.1097/WCO.0000000000001226 -
Practical Neurology Nov 2023Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving...
Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving sublingual nitroglycerine after 15 min, while monitoring beat-to-beat blood pressure (BP) and recording on video. Tilt testing is time-consuming but it is clinically useful and can guide therapy. Complications are rare. Syncope types include vasovagal syncope where BP falls after >3 min of tilt-up and later the heart rate falls; classic orthostatic hypotension where there is an immediate, progressive BP fall with minimal heart rate change; delayed orthostatic hypotension with a late BP fall after a stable phase but little or no heart rate rise; psychogenic pseudosyncope with apparent loss of consciousness, but no BP fall and a moderate heart rate rise; and postural orthostatic tachycardia syndrome where there is a significant heart rate rise but no BP fall.
Topics: Humans; Hypotension, Orthostatic; Tilt-Table Test; Syncope; Syncope, Vasovagal; Heart Rate; Blood Pressure
PubMed: 37726165
DOI: 10.1136/pn-2023-003749 -
Cardiology Clinics Aug 2023Sinus node dysfunction (SND) is a multifaceted disorder most prevalent in older individuals, but may also occur at an earlier age. In most cases, the SND diagnosis is... (Review)
Review
Sinus node dysfunction (SND) is a multifaceted disorder most prevalent in older individuals, but may also occur at an earlier age. In most cases, the SND diagnosis is ultimately established by documenting its ECG manifestations. EPS has limited utility. The treatment strategy is largely dictated by symptoms and ECG manifestations. Not infrequently, both bradycardia and tachycardia coexist in the same patients, along with other diseases common in the elderly (e.g., hypertension, coronary artery disease), thereby complicating treatment strategy. Prevention of the adverse consequences of both bradyarrhythmia and tachyarrhythmia is important to reduce susceptibility to syncope, falls, and thromboembolic complications.
Topics: Humans; Aged; Sick Sinus Syndrome; Bradycardia; Syncope; Electrocardiography
PubMed: 37321686
DOI: 10.1016/j.ccl.2023.03.013 -
Medicina Clinica Jun 2024
Topics: Humans; Syncope
PubMed: 38388319
DOI: 10.1016/j.medcli.2023.12.014