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Deep Brain Stimulation of the Periaqueductal Grey Induces Vasodilation in Humans

2011; Lippincott Williams & Wilkins; Volume: 57; Issue: 5 Linguagem: Inglês

10.1161/hypertensionaha.111.170183

1524-4563

Howard H. Carter, Ellen A. Dawson, N. Timothy Cable, Shanika D. Basnayake, Tipu Z. Aziz, Alexander L. Green, David J. Paterson, Christopher R. P. Lind, Dick H. J. Thijssen, Daniel J. Green,

Nitric Oxide and Endothelin Effects

HomeHypertensionVol. 57, No. 5Deep Brain Stimulation of the Periaqueductal Grey Induces Vasodilation in Humans Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBDeep Brain Stimulation of the Periaqueductal Grey Induces Vasodilation in Humans Howard H. Carter, Ellen A. Dawson, N. Timothy Cable, Shanika Basnayake, Tipu Z. Aziz, Alexander L. Green, David J. Paterson, Christopher R.P. Lind, Dick H.J. Thijssen and Daniel J. Green Howard H. CarterHoward H. Carter , Ellen A. DawsonEllen A. Dawson , N. Timothy CableN. Timothy Cable , Shanika BasnayakeShanika Basnayake , Tipu Z. AzizTipu Z. Aziz , Alexander L. GreenAlexander L. Green , David J. PatersonDavid J. Paterson , Christopher R.P. LindChristopher R.P. Lind , Dick H.J. ThijssenDick H.J. Thijssen and Daniel J. GreenDaniel J. Green Originally published14 Mar 2011https://doi.org/10.1161/HYPERTENSIONAHA.111.170183Hypertension. 2011;57:e24–e25Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:Surgical implantation of electrodes into deep brain structures for the management of conditions such as chronic pain provides an opportunity for assessment of the physiological impact of stimulation of focal brain nuclei in humans.1 Recent studies in humans have suggested that stimulation of the periventricular (PVG)/periaqueductal grey (PAG) regions can result in changes in systemic blood pressure (BP).2,3 In the present case, we examined the physiological impact of such stimulation in humans by obtaining continuous measures of limb blood flow, peripheral resistance, stroke volume, and heart rate (HR) during deep brain stimulation (DBS) of the PVG/PAG. The patient, a 55-year–old woman, was referred for management of recalcitrant chronic neuropathic, phantom limb pain (affecting both lower limbs) in 2004, subsequently leading to PVG/PAG DBS surgery in 2005 at the Radcliffe Infirmary in Oxford.Assessments and procedures were approved by the Oxford Ethics Committee and performed in a quiet thermostatically controlled room (26°C). The patient was placed in a semirecumbent position, at which point the stimulator was turned off for an initial 20-minute rest period. After a baseline BP assessment using a Finometer PRO (Finapres Medical Systems, Amsterdam, Netherlands), the stimulator was turned on, and BP, stroke volume, total peripheral resistance, and brachial artery diameter and blood flow velocity (Terason T3000, Teratech Corporation, Burlington, MA) were recorded for 5 minutes of this "on" period. Activation of the 2 proximal contacts in single bipolar arrangement on the model 3389 quadripolar lead (Medtronic, Minneapolis, MN) was set to a frequency of 40 Hz with a pulse width of 450 μs and amplitude of 3.1 V.The patient's mean brachial BP increased transiently when the stimulator was turned on but then persistently decreased below resting values (103±2 to 96±2 mm Hg; see Figure). This decrease in BP was associated with a contemporaneous increase in brachial artery blood flow (72±11 to 148±12 mL/min) and decrease in total peripheral resistance (15.2±0.6 to 12.9±0.5 mm Hg · mL−1min−1). Stroke volume increased (79±2 to 89±3 mL) along with cardiac output (6.7±0.2 to 7.5±0.3 L/min), whereas RR intervals (and HR) remained relatively stable throughout the rest and stimulation periods (0.70±0.02 versus 0.71±0.02 seconds).Download figureDownload PowerPointFigure. Mean brachial blood pressure, brachial blood flow, total peripheral resistance, cardiac output, stroke volume, and RR interval (heart rate) before and during stimulation.Although this report is consistent with previous studies describing changes in BP in awake humans during PVG/PAG stimulation,2,3 it is the first to our knowledge to report changes in vascular tone and peripheral resistance in response to DBS in humans. We observed an initial brief spike in BP, possibly relating to transient facial pain lasting 5 seconds when the stimulator was activated. Once the pain resolved, BP dropped rapidly and consistently, accompanied by a decrease in total peripheral resistance. Blood flow increased through the brachial artery, whereas brachial diameter remained relatively constant, suggesting that changes in the vasomotor tone of resistance vessels downstream were responsible for the changes in flow and pressure.We interpret the data from this subject as being consistent with a primary impact of DBS on vascular tone, as both BP and blood flow data rapidly and simultaneously changed after stimulation. Blood pressure is, of course, a highly regulated variable, and any decrease would be expected to induce reflex homeostatic responses. In this context, we might have expected some compensatory increase in cardiac output and/or peripheral resistance as stimulation continued, with emphasis on the cardiac change if the vasculature is indeed primarily modulated by stimulation. The persistent impact on both total peripheral resistance and blood flow throughout stimulation, in contrast to the gradual rise in cardiac output across this period, argues for a primary role of DBS on the vasculature. Baroreflex activation might have been expected to modify HR as well as stroke volume; however, the modest drop in BP may have been insufficient to stimulate a reflex response because HR did not appreciably change during stimulation, consistent with the previous report.2An important limitation of case presentations lies in their limited generalizability. We cannot assume, from this report, that all patients undergoing this procedure will exhibit similar hemodynamic changes on stimulation. It is likely, as with other physiological responses, that "responders" and "nonresponders" will exist, and such variability in hemodynamic responses is accentuated by small inconsistencies in electrode positioning. Indeed, the original report describing the BP effects of PAG DBS in humans observed responses in some, but not all, subjects.2In summary, these combined blood flow and pressure data suggest that stimulation of the PVG/PAG can impact vasomotor control. This finding compliments previous reports pertaining to the impact of DBS on BP and extends findings to the vasculature in humans.2,3Howard H. Carter School of Sport Science, Exercise and Health University of Western Australia Crawley, Western Australia, AustraliaEllen A. DawsonN. Timothy Cable Research Institute for Sport and Exercise Science Liverpool John Moore's University Liverpool, United KingdomShanika BasnayakeTipu Z. AzizAlexander L. GreenDavid J. Paterson Nuffield Department of Surgery and Department of Physiology, Anatomy, and Genetics University of Oxford Oxford, United KingdomChristopher R.P. Lind Department of Neurosurgery Sir Charles Gairdner Hospital Perth, Western Australia, Australia School of Surgery University of Western Australia Crawley, Western Australia, AustraliaDick H.J. Thijssen Research Institute for Sport and Exercise Science Liverpool John Moore's University Liverpool, United Kingdom Department of Physiology Radboud University Nijmegen Medical Centre Nijmegen, The NetherlandsDaniel J. Green School of Sport Science, Exercise and Health University of Western Australia Crawley, Western Australia, Australia Research Institute for Sport and Exercise Science Liverpool John Moore's University Liverpool, United KingdomAcknowledgmentsWe sincerely thank the patient involved in this experiment and the nursing and surgical staff who assisted.Sources of FundingThe study was supported by the National Institute for Health Research Biomedical Research Centre Award to the University of Oxford.The research of D.J.G. is supported by the Australian Research Council and National Heart Foundation. H.H.C. was supported by a University of Western Australia Research Collaboration Award. E.A.D. was supported by a Liverpool John Moores University Research Development Award.DisclosuresT.Z.A. received a Research grant (Wellcome Grant >$10K) and a Speakers Bureau (Integra LifeSciences >$10K). A.L.G. received Research grants (British Heart Foundation, Medtronic, Inc, and St Jude Medical, all >$10K), a Speakers Bureau (Integra LifeSciences <$10K), and Honoraria (St Jude Medical <$10K).FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. References 1. Green AL, Paterson DJ. Identification of neurocircuitry controlling cardiovascular function in humans using functional neurosurgery: implications for exercise control. Exp Physiol.2008; 93:1022–1028.CrossrefMedlineGoogle Scholar2. Green AL, Wang S, Owen SLF, Xie K, Liu X, Paterson DJ, Stein JF, Bain PG, Aziz TZ. Deep brain stimulation can regulate arterial blood pressure in awake humans. Neuroreport.2005; 16:1741–1745.CrossrefMedlineGoogle Scholar3. Green AL, Wang S, Bittar RG, Owen SLF, Paterson DJ, Stein JF, Bain PG, Shlugman D, Aziz TZ. Deep brain stimulation: a new treatment for hypertension?J Clin Neurosci.2007; 14:592–595.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Bolignano D (2020) Nonpharmacological therapies for uncontrolled hypertension Emerging Technologies for Heart Diseases, 10.1016/B978-0-12-813704-8.00046-2, (1039-1064), . Hyam J, Roy H, Huang Y, Martin S, Wang S, Rippey J, Coyne T, Stewart I, Kerr G, Silburn P, Paterson D, Aziz T and Green A (2019) Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation, Clinical Autonomic Research, 10.1007/s10286-019-00634-8, 29:6, (615-624), Online publication date: 1-Dec-2019. Ng F, Saxena M, Mahfoud F, Pathak A and Lobo M (2016) Device-based Therapy for Hypertension, Current Hypertension Reports, 10.1007/s11906-016-0670-5, 18:8, Online publication date: 1-Aug-2016. Hyam J, Aziz T and Green A (2014) Control of the Lungs via the Human Brain Using Neurosurgery The Central Nervous System Control of Respiration, 10.1016/B978-0-444-63274-6.00018-7, (341-366), . Lovick T (2013) Deep brain stimulation and autonomic control, Experimental Physiology, 10.1113/expphysiol.2013.072694, 99:2, (320-325), Online publication date: 1-Feb-2014. Alnima T, Kroon A and de Leeuw P (2014) Baroreflex activation therapy for patients with drug-resistant hypertension, Expert Review of Cardiovascular Therapy, 10.1586/14779072.2014.931226, 12:8, (955-962), Online publication date: 1-Aug-2014. Santisteban M, Zubcevic J, Baekey D and Raizada M (2013) Dysfunctional Brain-bone Marrow Communication: A Paradigm Shift in the Pathophysiology of Hypertension, Current Hypertension Reports, 10.1007/s11906-013-0361-4, 15:4, (377-389), Online publication date: 1-Aug-2013. Hyam J, Kringelbach M, Silburn P, Aziz T and Green A (2012) The autonomic effects of deep brain stimulation—a therapeutic opportunity, Nature Reviews Neurology, 10.1038/nrneurol.2012.100, 8:7, (391-400), Online publication date: 1-Jul-2012. Laurent S, Schlaich M and Esler M (2012) New drugs, procedures, and devices for hypertension, The Lancet, 10.1016/S0140-6736(12)60825-3, 380:9841, (591-600), Online publication date: 1-Aug-2012. Kobalava Z, Kotovskaya Y, Villevalde S, Amirbegishvili I and Solovyova A (2013) MANAGEMENT OF HYPERTENSION: NEW PERSPECTIVES, "Arterial'naya Gipertenziya" ("Arterial Hypertension"), 10.18705/1607-419X-2013-19-4-280-289, 19:4, (280-289) Basiago A and Binder D (2016) Effects of Deep Brain Stimulation on Autonomic Function, Brain Sciences, 10.3390/brainsci6030033, 6:3, (33) Ems R, Garg A, Ostergard T and Miller J (2019) Potential Deep Brain Stimulation Targets for the Management of Refractory Hypertension, Frontiers in Neuroscience, 10.3389/fnins.2019.00093, 13 May 2011Vol 57, Issue 5 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.111.170183PMID: 21403090 Originally publishedMarch 14, 2011 PDF download Advertisement SubjectsBasic Science ResearchVascular Biology