The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial
Background: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ab...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/100088 |
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| author | Gansheng Tan Anna L Huguenard Kara M Donovan Phillip Demarest Xiaoxuan Liu Ziwei Li Markus Adamek Kory Lavine Ananthv K Vellimana Terrance T Kummer Joshua W Osbun Gregory J Zipfel Peter Brunner Eric C Leuthardt |
| author_facet | Gansheng Tan Anna L Huguenard Kara M Donovan Phillip Demarest Xiaoxuan Liu Ziwei Li Markus Adamek Kory Lavine Ananthv K Vellimana Terrance T Kummer Joshua W Osbun Gregory J Zipfel Peter Brunner Eric C Leuthardt |
| author_sort | Gansheng Tan |
| collection | DOAJ |
| description | Background: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function.
Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement.
Results: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen’s d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge.
Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment.
Funding: The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB).
Clinical trial number: NCT04557618. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-15590d85ed6b4d1ab606948a44c883462025-01-21T11:07:29ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.100088The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trialGansheng Tan0https://orcid.org/0000-0001-8785-9499Anna L Huguenard1Kara M Donovan2Phillip Demarest3Xiaoxuan Liu4Ziwei Li5Markus Adamek6https://orcid.org/0000-0001-8519-9212Kory Lavine7Ananthv K Vellimana8Terrance T Kummer9https://orcid.org/0000-0001-8938-8280Joshua W Osbun10Gregory J Zipfel11Peter Brunner12https://orcid.org/0000-0002-2588-2754Eric C Leuthardt13https://orcid.org/0000-0003-4154-3135Department of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neuroscience, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Neurology, Washington University in St. Louis, St Louis, United StatesDepartment of Neurology, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Neurology, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesDepartment of Neurosurgery, Washington University School of Medicine, Springfield, United States; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, United StatesBackground: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function. Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement. Results: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen’s d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge. Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment. Funding: The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB). Clinical trial number: NCT04557618.https://elifesciences.org/articles/100088transcutaneous auricular vagus nerve stimulationsubarachnoid hemorrhagecardiovascularautonomic balanceheart rate variability |
| spellingShingle | Gansheng Tan Anna L Huguenard Kara M Donovan Phillip Demarest Xiaoxuan Liu Ziwei Li Markus Adamek Kory Lavine Ananthv K Vellimana Terrance T Kummer Joshua W Osbun Gregory J Zipfel Peter Brunner Eric C Leuthardt The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial eLife transcutaneous auricular vagus nerve stimulation subarachnoid hemorrhage cardiovascular autonomic balance heart rate variability |
| title | The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial |
| title_full | The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial |
| title_fullStr | The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial |
| title_full_unstemmed | The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial |
| title_short | The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial |
| title_sort | effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients a randomized trial |
| topic | transcutaneous auricular vagus nerve stimulation subarachnoid hemorrhage cardiovascular autonomic balance heart rate variability |
| url | https://elifesciences.org/articles/100088 |
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