04347nas a2200433 4500008004100000022001400041245015100055210006900206260001600275490000700291520297600298653001003274653000903284653001903293653002403312653001103336653001503347653001103362653000903373653001603382653002803398653004603426653002803472100001803500700002303518700002103541700002203562700001803584700001403602700001903616700001703635700002603652700002403678700002103702700002303723700001903746700002303765856012503788 2025 eng d a2050-084X00aThe effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.0 aeffect of transcutaneous auricular vagus nerve stimulation on ca c2025 Jan 090 v133 a

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 = 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.

10aAdult10aAged10aBlood Pressure10aElectrocardiography10aFemale10aHeart Rate10aHumans10aMale10aMiddle Aged10aSubarachnoid Hemorrhage10aTranscutaneous Electric Nerve Stimulation10aVagus Nerve Stimulation1 aTan, Gansheng1 aHuguenard, Anna, L1 aDonovan, Kara, M1 aDemarest, Phillip1 aLiu, Xiaoxuan1 aLi, Ziwei1 aAdamek, Markus1 aLavine, Kory1 aVellimana, Ananthv, K1 aKummer, Terrance, T1 aOsbun, Joshua, W1 aZipfel, Gregory, J1 aBrunner, Peter1 aLeuthardt, Eric, C uhttps://www.neurotechcenter.org/publications/2025/effect-transcutaneous-auricular-vagus-nerve-stimulation-cardiovascular