FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3134157054> ?p ?o ?g. }

• W3134157054 endingPage "1247" @default.
• W3134157054 startingPage "1245" @default.
• W3134157054 abstract "HomeHypertensionVol. 77, No. 4Run Vagus Run Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBRun Vagus RunCardiovagal Baroreflex Function and the Postural Tachycardia Syndrome Leopold Lecheler, Fabian Hoffmann, Jens Tank, Jens Jordan Leopold LechelerLeopold Lecheler https://orcid.org/0000-0003-2517-7358 From the DLR-German Aerospace Center, Institute for Aerospace Medicine, Cologne, Germany (L.L., F.H., J.T., J.J.) Search for more papers by this author , Fabian HoffmannFabian Hoffmann https://orcid.org/0000-0002-3199-9924 From the DLR-German Aerospace Center, Institute for Aerospace Medicine, Cologne, Germany (L.L., F.H., J.T., J.J.) Search for more papers by this author , Jens TankJens Tank From the DLR-German Aerospace Center, Institute for Aerospace Medicine, Cologne, Germany (L.L., F.H., J.T., J.J.) Search for more papers by this author and Jens JordanJens Jordan Correspondence to: Jens Jordan, Institute for Aerospace Medicine, Linder Hoehe, 51147 Cologne, Germany. Email: E-mail Address: [email protected] https://orcid.org/0000-0003-4518-0706 From the DLR-German Aerospace Center, Institute for Aerospace Medicine, Cologne, Germany (L.L., F.H., J.T., J.J.) Chair of Aerospace Medicine, Medical Faculty, University of Cologne, Germany (J.J.). Search for more papers by this author Originally published10 Mar 2021https://doi.org/10.1161/HYPERTENSIONAHA.121.16578Hypertension. 2021;77:1245–1247This article is a commentary on the followingSupine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia SyndromeSee related article, pp 1234–1244The study by Stewart et al1 in this issue, which was conducted in patients with the postural tachycardia syndrome (POTS), reminds us that parasympathetic activity could be modulated to treat human cardiovascular disease. Sympathetic and parasympathetic efferent nerves regulate heart rate and blood pressure. Sympathetic activation raises heart rate, vascular tone, and renal sodium reabsorption. The latter results from sympathetically mediated renin release and direct tubular actions. In contrast, parasympathetic activation lowers heart rate primarily at the level of the cardiac sinus node. An imbalance between cardiovascular sympathetic and parasympathetic activity with sympathetic predominance has been observed in various cardiovascular disorders and heralds increased cardiovascular morbidity and mortality. Therefore, sympathetic inhibition be it through pharmacological agents or interventional procedures is widely applied in cardiovascular medicine. β-Blockade in patients with heart failure and reduced ejection fraction or following myocardial infarction is a prime example. The idea that parasympathetic nervous system activation could have a benefit received surprisingly little attention.Precise baroreflex-mediated adjustments in sympathetic and parasympathetic activity enable human beings to cope with hemodynamic challenges imposed by standing. Indeed, with assumption of the upright posture, ≈500 to 1000 mL blood is pooled in veins below the diaphragm and 10% to 20% plasma volume escapes the vascular compartment. Altered cardiovascular autonomic control mechanisms are often unmasked with standing. POTS, which is the most common orthostatic intolerance syndrome, is characterized by orthostatic tachycardia associated with symptoms but without orthostatic hypotension.2 The true prevalence is unknown. Crude estimates based on the proportion of patients diagnosed with POTS in specialized centers suggest that at least 500 000 people in the United States are affected. The Figure shows beat-by-beat blood pressure and heart rate tracings in a patient with POTS in the supine and in the upright position. POTS can be the expression of heterogenous underlying mechanisms including cardiovascular deconditioning, hypovolemia, excess venous pooling, neuropathic changes,3 autoimmune mechanisms, mast cell activation, and norepinephrine transporter deficiency.4 In any event, excess sympathetic activity and reduced parasympathetic activity can, both, contribute to the POTS phenotype.5Download figureDownload PowerPointFigure. Active standing test of a 19-y-old female patient with the postural tachycardia syndrome. After 7 min, the test had to be aborted due to increasing symptoms. The patient experienced shortness of breath, thoracic discomfort, hot flashes, shivering, fatigue, and impaired concentration. MAP indicates mean arterial pressure; and max HR, maximum heart rate.Many patients with POTS experience chronic, often debilitating symptoms that are difficult to manage. Nonpharmacological treatments such as exercise programs, compression garments, increased dietary sodium ingestion, and water drinking can provide symptomatic relief. Some patients require regular intravenous volume loading. Pharmacological POTS therapies are largely based on anecdotal evidence or small-scale studies and are often not approved for this indication. The mineralocorticoid fludrocortisone, the α-adrenoreceptor agonist midodrine, and low-dose β-blockade have been utilized with mixed results. Selective pacemaker channel inhibition with ivabradine, which is not available in all countries, may have utility in some patients with POTS. Suffice it to say that more effective and well-tolerated therapies are badly needed.Stewart et al1 assessed baroreflex heart rate control in adolescents and younger adults with POTS and in matched control people. In patients with POTS, they repeated baroreflex testing following acute treatment with digoxin and pyridostigmine to test whether a cardiovagal baroreflex deficit could be corrected. Pyridostigmine increases cardiac vagal drive through acetylcholinesterase inhibition. Digoxin appears to increase vagal tone through baroreflex sensitization. The authors utilized the reference standard modified Oxford method with sequential intravenous sodium nitroprusside and phenylephrine injection to generate full sigmoidal cardiovagal baroreflex curves. In contrast, commonly applied noninvasive methodologies such as the sequence method or cross-spectral analysis only capture this curve in the vicinity of the operating point. A particular strength of the study is that comprehensive baroreflex testing was conducted in the supine and in the upright positions, which is relevant for a condition associated with orthostatic symptoms.Patients with POTS exhibited substantial changes in several aspects of the baroreflex heart rate curve in the supine position and more so when standing. Compared with control persons, the operating point was shifted to higher heart rates and located on a different portion of the baroreflex curve. These changes could conceivably predispose to altered cardiovascular control in POTS. Both pyridostigmine and digoxin partly reversed some aspects of the cardiovagal baroreflex abnormality in POTS patients. None completely abolished orthostatic tachycardia.An important limitation of the study is that both medications do not selectively engage cardiovagal activity. For example, pyridostigmine also affects efferent sympathetic activity. Another limitation is that owing to its long half-life, digoxin was tested as the last intervention, which may have introduced a bias. Despite these issues, the authors have to be congratulated for conducting an involved physiological study in POTS patients that provides insight in underlying mechanisms and potential treatment targets for POTS. Perhaps, cardiac parasympathetic control also deserves more attention in other cardiovascular medicine areas. The retrospective observation that patients with dementia treated with the acetylcholinesterase inhibitor donepezil exhibited reduced cardiovascular mortality, which has to be interpreted with caution, is, nevertheless, reassuring.6Prerequisites for advances in the field are better methodologies to study parasympathetic cardiovascular control mechanisms. Studying sympathetic cardiovascular control in human beings is by no means trivial. Yet, a wide range of methodologies including direct measurements of efferent sympathetic traffic through microneurography, detailed biochemical norepinephrine turnover assessment, pharmacological approaches, and imaging using specific radiolabeled tracers allows detailed mechanism-oriented investigations in human beings. The methodological armamentarium is limited when it comes to cardiovascular parasympathetic control mechanisms. Heart rate variability and baroreflex analysis provide valuable albeit limited insight. The main parasympathetic neurotransmitter acetylcholine has a short half-life, and efferent cardiac vagal nerves cannot be reasonably impaled with recording electrodes in human beings. Perhaps, advances in pharmacological approaches7 or functional brain stem imaging covering areas regulating efferent vagal activity could advance the field. Another important question is how cardiac vagal activity could be raised in a more selective and safe fashion. Pyridostigmine and digoxin while providing insight in POTS pathophysiology are probably not suitable for long-term therapy in this indication given their nonspecific actions, side effects, and limited efficacy in reversing the baroreflex abnormality in POTS. Another issue that ought to be addressed is how cardiac vagal activity could be enhanced without raising the risk for potentially dangerous bradycardia or asystole. Meanwhile, the safest nonpharmacological approach improving cardiac vagal activity is physical exercise, which should be part of a comprehensive POTS treatment strategy anyway.AcknowledgmentsAll authors contributed to the making of the article and approved the data and conclusions in the article.Sources of FundingF. Hoffmann was supported by Deutsches Zentrum für Luft- und Raumfahrt/German Aerospace Center grant 50WB1816.Disclosures J. Jordan served as a consultant for Novartis, Novo-Nordisk, Boehringer Ingelheim, Sanofi, Theravance, and Vivus and is the cofounder of Eternygen GmbH. J. Tank receives research support from Boehringer Ingelheim. The others report no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 1247.Correspondence to: Jens Jordan, Institute for Aerospace Medicine, Linder Hoehe, 51147 Cologne, Germany. Email: jens.[email protected]deReferences1. Stewart JM, Warsy IA, Visintainer P, Terilli C, Medow MS. Supine parasympathetic withdrawal and upright sympathetic activation underly abnormalities of the baroreflex in postural tachycardia syndrome: effects of pyridostigmine and digoxin.Hypertension. 2021; 77:1234–1244. doi: 10.1161/HYPERTENSIONAHA.120.16113LinkGoogle Scholar2. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, et al.. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.Clin Auton Res. 2011; 21:69–72. doi: 10.1007/s10286-011-0119-5CrossrefMedlineGoogle Scholar3. Jacob G, Costa F, Shannon JR, Robertson RM, Wathen M, Stein M, Biaggioni I, Ertl A, Black B, Robertson D. The neuropathic postural tachycardia syndrome.N Engl J Med. 2000; 343:1008–1014. doi: 10.1056/NEJM200010053431404CrossrefMedlineGoogle Scholar4. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency.N Engl J Med. 2000; 342:541–549. doi: 10.1056/NEJM200002243420803CrossrefMedlineGoogle Scholar5. Jacob G, Diedrich L, Sato K, Brychta RJ, Raj SR, Robertson D, Biaggioni I, Diedrich A. Vagal and sympathetic function in neuropathic postural tachycardia syndrome.Hypertension. 2019; 73:1087–1096. doi: 10.1161/HYPERTENSIONAHA.118.11803LinkGoogle Scholar6. Sato K, Urbano R, Yu C, Yamasaki F, Sato T, Jordan J, Robertson D, Diedrich A. The effect of donepezil treatment on cardiovascular mortality.Clin Pharmacol Ther. 2010; 88:335–338. doi: 10.1038/clpt.2010.98CrossrefMedlineGoogle Scholar7. Tank J, Heusser K, Diedrich A, Luft FC, Jordan J. A novel pharmacological approach to determining parasympathetic heart rate reserve in human subjects.Clin Pharmacol Ther. 2010; 88:630–633. doi: 10.1038/clpt.2010.177CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesSupine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia SyndromeJulian M. Stewart, et al. Hypertension. 2021;77:1234-1244 April 2021Vol 77, Issue 4Article InformationMetrics Download: 995 © 2021 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.121.16578PMID: 33689465 Originally publishedMarch 10, 2021 PDF download SubjectsCardiovascular DiseaseAutonomic Nervous System" @default.
• W3134157054 created "2021-03-15" @default.
• W3134157054 creator A5004550002 @default.
• W3134157054 creator A5017690840 @default.
• W3134157054 creator A5079071222 @default.
• W3134157054 creator A5089388570 @default.
• W3134157054 date "2021-04-01" @default.
• W3134157054 modified "2023-09-26" @default.
• W3134157054 title "Run Vagus Run" @default.
• W3134157054 cites W1975574577 @default.
• W3134157054 cites W2068172379 @default.
• W3134157054 cites W2086567283 @default.
• W3134157054 cites W2133465432 @default.
• W3134157054 cites W2323218437 @default.
• W3134157054 cites W2921667665 @default.
• W3134157054 cites W3120220251 @default.
• W3134157054 doi "https://doi.org/10.1161/hypertensionaha.121.16578" @default.
• W3134157054 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33689465" @default.
• W3134157054 hasPublicationYear "2021" @default.
• W3134157054 type Work @default.
• W3134157054 sameAs 3134157054 @default.
• W3134157054 citedByCount "0" @default.
• W3134157054 crossrefType "journal-article" @default.
• W3134157054 hasAuthorship W3134157054A5004550002 @default.
• W3134157054 hasAuthorship W3134157054A5017690840 @default.
• W3134157054 hasAuthorship W3134157054A5079071222 @default.
• W3134157054 hasAuthorship W3134157054A5089388570 @default.
• W3134157054 hasBestOaLocation W31341570541 @default.
• W3134157054 hasConcept C126322002 @default.
• W3134157054 hasConcept C164705383 @default.
• W3134157054 hasConcept C71924100 @default.
• W3134157054 hasConceptScore W3134157054C126322002 @default.
• W3134157054 hasConceptScore W3134157054C164705383 @default.
• W3134157054 hasConceptScore W3134157054C71924100 @default.
• W3134157054 hasIssue "4" @default.
• W3134157054 hasLocation W31341570541 @default.
• W3134157054 hasOpenAccess W3134157054 @default.
• W3134157054 hasPrimaryLocation W31341570541 @default.
• W3134157054 hasRelatedWork W2011347913 @default.
• W3134157054 hasRelatedWork W2049397185 @default.
• W3134157054 hasRelatedWork W2073151595 @default.
• W3134157054 hasRelatedWork W2074833529 @default.
• W3134157054 hasRelatedWork W2125804349 @default.
• W3134157054 hasRelatedWork W2159512267 @default.
• W3134157054 hasRelatedWork W2304633692 @default.
• W3134157054 hasRelatedWork W2355498105 @default.
• W3134157054 hasRelatedWork W2399063111 @default.
• W3134157054 hasRelatedWork W2414320482 @default.
• W3134157054 hasVolume "77" @default.
• W3134157054 isParatext "false" @default.
• W3134157054 isRetracted "false" @default.
• W3134157054 magId "3134157054" @default.
• W3134157054 workType "article" @default.