<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tan, Gansheng</style></author><author><style face="normal" font="default" size="100%">Huguenard, Anna L</style></author><author><style face="normal" font="default" size="100%">Donovan, Kara M</style></author><author><style face="normal" font="default" size="100%">Demarest, Phillip</style></author><author><style face="normal" font="default" size="100%">Liu, Xiaoxuan</style></author><author><style face="normal" font="default" size="100%">Li, Ziwei</style></author><author><style face="normal" font="default" size="100%">Adamek, Markus</style></author><author><style face="normal" font="default" size="100%">Lavine, Kory</style></author><author><style face="normal" font="default" size="100%">Vellimana, Ananthv K</style></author><author><style face="normal" font="default" size="100%">Kummer, Terrance T</style></author><author><style face="normal" font="default" size="100%">Osbun, Joshua W</style></author><author><style face="normal" font="default" size="100%">Zipfel, Gregory J</style></author><author><style face="normal" font="default" size="100%">Brunner, Peter</style></author><author><style face="normal" font="default" size="100%">Leuthardt, Eric C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.</style></title><secondary-title><style face="normal" font="default" size="100%">Elife</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Elife</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Blood Pressure</style></keyword><keyword><style  face="normal" font="default" size="100%">Electrocardiography</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Rate</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Subarachnoid Hemorrhage</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcutaneous Electric Nerve Stimulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Vagus Nerve Stimulation</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2025 Jan 09</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">13</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;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  = 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;FUNDING: &lt;/b&gt;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).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CLINICAL TRIAL NUMBER: &lt;/b&gt;NCT04557618.&lt;/p&gt;</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tan, Gansheng</style></author><author><style face="normal" font="default" size="100%">Huguenard, Anna L</style></author><author><style face="normal" font="default" size="100%">Donovan, Kara M</style></author><author><style face="normal" font="default" size="100%">Demarest, Phillip</style></author><author><style face="normal" font="default" size="100%">Liu, Xiaoxuan</style></author><author><style face="normal" font="default" size="100%">Li, Ziwei</style></author><author><style face="normal" font="default" size="100%">Adamek, Markus</style></author><author><style face="normal" font="default" size="100%">Lavine, Kory</style></author><author><style face="normal" font="default" size="100%">Vellimana, Ananth K</style></author><author><style face="normal" font="default" size="100%">Kummer, Terrance T</style></author><author><style face="normal" font="default" size="100%">Osbun, Joshua W</style></author><author><style face="normal" font="default" size="100%">Zipfel, Gregory J</style></author><author><style face="normal" font="default" size="100%">Brunner, Peter</style></author><author><style face="normal" font="default" size="100%">Leuthardt, Eric C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.</style></title><secondary-title><style face="normal" font="default" size="100%">medRxiv</style></secondary-title><alt-title><style face="normal" font="default" size="100%">medRxiv</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Sep 08</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;INTRODUCTION: &lt;/b&gt;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, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;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 (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2-4 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, intracranial pressure, or heart rate variability. 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;TRIAL REGISTRATION: &lt;/b&gt;NCT04557618.&lt;/p&gt;</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Huguenard, Anna L</style></author><author><style face="normal" font="default" size="100%">Tan, Gansheng</style></author><author><style face="normal" font="default" size="100%">Johnson, Gabrielle W</style></author><author><style face="normal" font="default" size="100%">Adamek, Markus</style></author><author><style face="normal" font="default" size="100%">Coxon, Andrew T</style></author><author><style face="normal" font="default" size="100%">Kummer, Terrance T</style></author><author><style face="normal" font="default" size="100%">Osbun, Joshua W</style></author><author><style face="normal" font="default" size="100%">Vellimana, Ananth K</style></author><author><style face="normal" font="default" size="100%">Limbrick, David D</style></author><author><style face="normal" font="default" size="100%">Zipfel, Gregory J</style></author><author><style face="normal" font="default" size="100%">Brunner, Peter</style></author><author><style face="normal" font="default" size="100%">Leuthardt, Eric C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial.</style></title><secondary-title><style face="normal" font="default" size="100%">medRxiv</style></secondary-title><alt-title><style face="normal" font="default" size="100%">medRxiv</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Mar 19</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints.&lt;/p&gt;&lt;p&gt;&lt;b&gt;MATERIALS AND METHODS: &lt;/b&gt;The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient's hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH.&lt;/p&gt;&lt;p&gt;&lt;b&gt;DISCUSSION: &lt;/b&gt;Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH.&lt;/p&gt;&lt;p&gt;&lt;b&gt;TRIAL REGISTRATION: &lt;/b&gt;Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021.&lt;/p&gt;</style></abstract></record></records></xml>