Clin Auton Res
· 2026 Jul · PMID 42393412
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PURPOSE: To review the cardiovascular effects of pharmacologic dopamine receptor modulation in humans, organized by receptor subtype. METHODS: Narrative review of human pharmacological, genetic, and clinical evidence lin...PURPOSE: To review the cardiovascular effects of pharmacologic dopamine receptor modulation in humans, organized by receptor subtype. METHODS: Narrative review of human pharmacological, genetic, and clinical evidence linking dopamine receptor agonism and antagonism to blood pressure and heart rate changes in healthy volunteers and in patients with Parkinson disease, autonomic failure, psychiatric disorders, and selected cardiovascular conditions. RESULTS: Dopaminergic receptor agonism generally lowers blood pressure, with the magnitude of hypotension tracking with intrinsic activity: full orthosteric agonists (bromocriptine, ropirinole, apomorphine) carry the highest risk of orthostatic hypotension, and partial agonists (tavapadon) produce attenuated but clinically relevant hypotension. Dopamine D3-preferring agents (PF-592379, mesdopetam, cariprazine) have neutral cardiovascular effects in short-term trials. Levodopa-induced orthostatic hypotension arises from at least five converging mechanisms whose clinical impact is amplified by underlying neurogenic orthostatic hypotension. A notable exception is mevidalen, a centrally acting dopamine D1 positive allosteric modulator that paradoxically raises blood pressure. Despite murine knockout models consistently predicting that dopamine receptor deletion produces hypertension, pharmacological antagonism in humans does not reliably raise blood pressure: dopamine D1, D2, and D3 antagonists show largely neutral cardiovascular profiles, while antipsychotic-associated orthostatic hypotension is driven primarily by α1-adrenergic blockade. CONCLUSIONS: The cardiovascular response to dopaminergic agents depends on receptor selectivity, intrinsic activity, and baroreflex integrity. The discrepancy between murine-knockout-predicted hypertension and human pharmacological neutrality with antagonists, and the hypertensive effects of dopamine D1 positive allosteric modulators, represent key unresolved questions.
Clin Auton Res
· 2026 Jul · PMID 42384146
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BACKGROUND: Vagus nerve stimulation (VNS) is a neuromodulatory intervention with antiinflammatory and autonomic regulatory properties. Although its clinical applications have primarily been explored in neurological disor...BACKGROUND: Vagus nerve stimulation (VNS) is a neuromodulatory intervention with antiinflammatory and autonomic regulatory properties. Although its clinical applications have primarily been explored in neurological disorders, its potential role in pulmonary and respiratory outcomes across preclinical and clinical settings remains incompletely characterized and dispersed across different study domains. This scoping review aimed to map the available evidence on the effects of VNS on the pulmonary and respiratory systems, with particular emphasis on inflammatory and autonomic mechanisms. METHODS: This scoping review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Three reviewers systematically searched PubMed, Web of Science, and the Cochrane Library for studies published between January 2020 and February 2026. Original preclinical and clinical studies investigating invasive or noninvasive VNS and reporting pulmonary, respiratory physiology, autonomic, or inflammatory outcomes were included. RESULTS: A total of 159 records were identified, of which 12 studies met the inclusion criteria. The evidence base was predominantly preclinical. In animal studies, invasive cervical VNS was frequently associated with reductions in pulmonary inflammation, histopathological lung injury, and proinflammatory cytokine expression. Clinical studies were limited and heterogeneous, but generally indicated variable modulation of autonomic function, including changes in parasympathetic activity, as well as heterogeneous effects on systemic inflammatory markers and limited respiratory outcomes. CONCLUSIONS: Current evidence suggests that VNS may modulate pulmonary inflammatory responses in preclinical models. However, clinical evidence remains limited and heterogeneous, particularly regarding autonomic and respiratory outcomes. Well-designed clinical trials using standardized stimulation protocols and predefined respiratory end points are needed to clarify its therapeutic potential in respiratory disorders.
Gagaouzova BS, van Rossum IA, Kerkhof FI
… +2 more, Thijs RD, van Dijk JG
Clin Auton Res
· 2026 Jun · PMID 42303928
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PURPOSE: Previous research regarding the association between blood pressure (BP) fall and symptoms yielded inconsistent results in classical orthostatic hypotension (cOH), with some studies proposing specific cut-off val...PURPOSE: Previous research regarding the association between blood pressure (BP) fall and symptoms yielded inconsistent results in classical orthostatic hypotension (cOH), with some studies proposing specific cut-off values and others reporting only weak or absent correlations. This study examined clinical cOH symptoms in relation to changes in BP and the haemodynamic parameters determining BP. METHODS: We retrospectively analysed 77 tilt test records showing cOH and selected 40 with and 37 without complaint recognition during the test. We compared absolute values of haemodynamic parameters as well as the differences and ratios compared to supine baseline at three different times during tilt. We also explored relationships between relative haemodynamic changes and symptoms with the log-ratio method. RESULTS: There was a larger blood pressure fall in the group with complaint recognition compared (49.2 vs 37.3, p = 0.043). The log-ratio analysis showed less total peripheral resistance increase and a larger blood pressure decrease in the symptomatic group. CONCLUSION: Recognised complaints were related to a larger BP fall, while in previous studies complaints were either not related to BP or to minimum BP. These contrasts suggest that the pathophysiology of orthostatic complaints is complex. The chain of events from low BP to awareness of complaints contains multiple links, of which cerebral perfusion is probably a critical one. We suggest that the pathway contains so much variability that we should not expect the relation between low blood pressure and complaints in cOH to be simple.
Brignole M, van Dijk JG, Fedorowski A
… +1 more, De Lange FJ
Clin Auton Res
· 2026 Jun · PMID 42240740
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PURPOSE: To elucidate the pathophysiology of the carotid sinus reflex in a large cohort of patients with suspected reflex syncope. METHOD: We reviewed an electronic database of patients with suspected reflex syncope who...PURPOSE: To elucidate the pathophysiology of the carotid sinus reflex in a large cohort of patients with suspected reflex syncope. METHOD: We reviewed an electronic database of patients with suspected reflex syncope who underwent carotid sinus massage. The diagnostic protocol included both right and left massage, in supine and upright positions, followed by tilt testing. RESULTS: The cohort included 2249 patients (52% male), median age 73 years. The conventional abnormality threshold of a maximum RR interval ≥ 3000 ms was present in 14.7% of patients and of a systolic blood pressure fall > 50 mmHg in 14.3% of patients. Abnormal responses occurred more frequently on the right side than the left side, and more during upright than supine testing. A second abnormal test occurred more often ipsilaterally. The extent of the maximum RR interval elicited by massage was independent of the baseline RR interval, whereas the difference in systolic blood pressure fall increased markedly with higher baseline values. The occurrence and severity of cardioinhibition and vasodepression increased with age, beginning at 40 years. Abnormal RR intervals and blood pressure drops were observed more frequently in men than in women. Additionally, there was only a limited correlation between positive responses to carotid massage and tilt testing concerning asystole and blood pressure reduction. CONCLUSION: Age, sex and initial systolic blood pressure strongly influence response to carotid sinus massage. Abnormal responses did not correlate with positive tilt test results, possibly as a result of opposing effects of age and sex on carotid sinus hypersensitivity and vasovagal syncope.
Clin Auton Res
· 2026 Jun · PMID 42236643
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PURPOSE: Heart rate variability (HRV) has been linked to cerebral small vessel disease (CSVD) development. This study aimed to investigate the relationship between white matter hyperintensity (WMH) and HRV in older patie...PURPOSE: Heart rate variability (HRV) has been linked to cerebral small vessel disease (CSVD) development. This study aimed to investigate the relationship between white matter hyperintensity (WMH) and HRV in older patients with CSVD. METHODS: Patients with CSVD aged ≥ 60 years, diagnosed via magnetic resonance imaging and treated at Tianjin Huanhu Hospital in October 2022-April 2023, were included. WMH burden was defined as periventricular (PV-WMH) or deep WMH (D-WMH), with Fazekas scores of 3 or 2-3, respectively. Modified WMH burden was categorized based on total Fazekas scores (PV-WMH + D-WMH): grade 0 for 0-2, grade 1 for 3-4, and grade 2 for 5-6. Patient demographics were documented, and HRV was analyzed through 10-min short-range electrocardiography recordings. Time-domain indices included standard deviation of N-N intervals, root-mean-squared differences of successive N-N intervals, and the proportion of N-N intervals exceeding 50 ms. Frequency-domain indices included low-frequency power (LF, 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.4 Hz), and LF/HF. Correlations were examined using univariable and multivariable analyses. RESULTS: Among 108 patients with CSVD (age 60-87 years; median 66.0 years [interquartile range 63.0-71.0]), WMH burden was associated with sex, age, stroke, LF, and LF/HF (p < 0.05), with LF/HF independently linked in multivariable analysis. Modified WMH burden showed similar associations and remained independently correlated with LF/HF (p < 0.05). CONCLUSIONS: The presence and severity of WMH in CSVD were related to decreased LF/HF. This is possibly due to decreased cardiac sympathetic activity, indicates that decreased LF/HF may be a potential risk factor for WMH, and can be detected via short HRV recordings.
de Lange FJ, Brignole M, Benditt DG
… +27 more, Dani M, Deharo JC, Fanciulli A, Fedorowski A, Groppelli A, Hamdan MH, Hamrefors V, de Jong JSY, Kenny RA, Kulakowski P, Moya A, Maggi R, Morillo CA, Olshansky B, Raj SR, Rice C, Rivasi G, van Rossum I, Russo V, Sheldon R, Shen WK, Sutton R, Thijs R, Taraborrelli P, Tomaino M, Ungar A, van Zanten S
Clin Auton Res
· 2026 May · PMID 42204029
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Carotid sinus massage (CSM) is essential in evaluating recurrent unexplained reflex syncope, as it uniquely identifies cardioinhibitory forms that other tests may miss. CSM is largely underused in clinical practice outsi...Carotid sinus massage (CSM) is essential in evaluating recurrent unexplained reflex syncope, as it uniquely identifies cardioinhibitory forms that other tests may miss. CSM is largely underused in clinical practice outside dedicated syncope facilities and, when performed, its execution varies, as does the interpretation of results. Underuse affects the diagnostic yield of CSM in the syncope evaluation, thereby denying patients mechanism-based personalized treatment. There are several barriers to the proper use of CSM in the work-up of patients with unexplained syncope.To address these important limitations, an international panel of experts in the field of syncope provide herein a consensus document with the aim of offering practical guidance for the indications, contraindications, and methodology for performing carotid sinus massage in general and dedicated syncope facilities and in the emergency department.
Bastos P, Kermorgant M, Fabbri M
… +10 more, Roche F, Pichot V, Ory-Magne F, Leung C, Rascol O, G Meissner W, Foubert-Samier A, Bendetowicz D, Proust Lima C, Pavy-le-Traon A
Clin Auton Res
· 2026 Jun · PMID 42033597
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Clin Auton Res
· 2026 Jun · PMID 42010088
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Orthostatic hypotension (OH), defined as a sustained reduction of ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic blood pressure within 3 minutes of standing, represents one of the most clinically significant manifestati...Orthostatic hypotension (OH), defined as a sustained reduction of ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic blood pressure within 3 minutes of standing, represents one of the most clinically significant manifestations of autonomic failure. Beyond its hemodynamic definition, OH is associated with disabling symptoms, falls, syncope, reduced quality of life, increased healthcare utilization, and excess mortality. In clinical practice, management often requires balancing objective blood pressure measurements with the patient's lived experience of orthostatic intolerance. This viewpoint argues that symptoms represent an appropriate and clinically meaningful target for screening and management of OH. Three central assumptions support this perspective. First, patients are reliable reporters of orthostatic symptoms and clinicians are capable interpreters of these reports. Validated patient-reported outcome measures, such as the Orthostatic Hypotension Questionnaire (OHQ), demonstrate that symptom burden and functional impairment can be reproducibly quantified and that clinically meaningful changes can be detected. Second, although the relationship between orthostatic blood pressure changes and symptoms is not absolute, evidence supports a clinically relevant association, with symptomatic individuals often experiencing greater cerebral hypoperfusion when upright. Third, symptoms serve as a practical proxy for meaningful OH-related outcomes, including functional independence, fall risk, and quality of life, and have been accepted as primary endpoints in pivotal clinical trials. A symptom-centered framework complements objective hemodynamic assessment by contextualizing physiological findings within patients' functional experience. Integrating symptom reporting with orthostatic measurements provides a pragmatic, patient-centered approach to screening, treatment decisions, and evaluation of therapeutic response in OH.
Clin Auton Res
· 2026 Apr · PMID 41964848
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We report a 71-year-old woman who developed disabling orthostatic tremor and severe orthostatic hypertension following cosmetic neck lift surgery. Autonomic testing demonstrated exaggerated pressor responses and excessiv...We report a 71-year-old woman who developed disabling orthostatic tremor and severe orthostatic hypertension following cosmetic neck lift surgery. Autonomic testing demonstrated exaggerated pressor responses and excessive orthostatic catecholamine release, consistent with sympathoadrenal overactivation due to impaired carotid baroreflex function. This case highlights a potential autonomic complication of aesthetic neck surgery.