Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes

Nirav Dhanesha; Thomas Schnell; Salam Rahmatalla; Jonathan DeShaw; Daniel Thedens; Bradley M Parker; M Bridget Zimmerman; Andrew A Pieper; Anil K Chauhan; Enrique C Leira

doi:10.1161/STROKEAHA.120.029405

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Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes

Journal article

Open access

Peer reviewed

Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes

Nirav Dhanesha, Thomas Schnell, Salam Rahmatalla, Jonathan DeShaw, Daniel Thedens, Bradley M Parker, M Bridget Zimmerman, Andrew A Pieper, Anil K Chauhan and Enrique C Leira

Stroke (1970), Vol.51(6), pp.1855-1861

06/2020

DOI: 10.1161/STROKEAHA.120.029405

PMCID: PMC7263385

PMID: 32397935

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Abstract

Background and Purpose- We aim to determine the potential impact on stroke thrombolysis of drip-and-ship helicopter flights and specifically of their low-frequency vibrations (LFVs). Methods- Mice with a middle cerebral artery autologous thromboembolic occlusion were randomized to receive rtPA (recombinant tissue-type plasminogen activator; or saline) 90 minutes later in 3 different settings: (1) a motion platform simulator that reproduced the LFV signature of the helicopter, (2) a standardized actual helicopter flight, and (3) a ground control. Results- Mice assigned to the LFV simulation while receiving tPA had smaller infarctions (31.6 versus 54.9 mm ; =0.007) and increased favorable neurological outcomes (86% versus 28%; =0.0001) when compared with ground controls. Surprisingly, mice receiving tPA in the helicopter did not exhibit smaller infarctions (47.8 versus 54.9 mm ; =0.58) nor improved neurological outcomes (37% versus 28%; =0.71). This could be due to a causative effect of the 20- to 30-Hz band, which was inadvertently attenuated during actual flights. Mice using saline showed no differences between the LFV simulator and controls with respect to infarct size (80.9 versus 95.3; =0.81) or neurological outcomes (25% versus 11%; =0.24), ruling out an effect of LFV alone. There were no differences in blood-brain barrier permeability between LFV simulator or helicopter, compared with controls (2.45-3.02 versus 4.82 mm ; =0.14). Conclusions- Vibration in the low-frequency range (0.5-120 Hz) is synergistic with rtPA, significantly improving the effectiveness of thrombolysis without impairing blood-brain barrier permeability. Our findings reveal LFV as a novel, safe, and simple-to-deliver intervention that could improve the outcomes of patients. Visual Overview- An online visual overview is available for this article.

Animals

Tissue Plasminogen Activator - pharmacology

Vibration

Thrombolytic Therapy

Male

Mice

Brain Infarction - therapy

Stroke - therapy

Disease Models, Animal

Details

Title: Subtitle: Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes
Creators: Nirav Dhanesha - From the Department of Internal Medicine, Carver College of Medicine (N.D., A.K.C.), University of Iowa
Thomas Schnell - Operator Performance Laboratory, Department of Industrial and System Engineering, College of Engineering (T.S., B.M.P.), University of Iowa
Salam Rahmatalla - Center for Computer-Aided Design, Department of Civil and Environmental Engineering, College of Engineering (S.R., J.D.), University of Iowa
Jonathan DeShaw - Center for Computer-Aided Design, Department of Civil and Environmental Engineering, College of Engineering (S.R., J.D.), University of Iowa
Daniel Thedens - Department of Radiology, Carver College of Medicine (D.T.), University of Iowa
Bradley M Parker - Operator Performance Laboratory, Department of Industrial and System Engineering, College of Engineering (T.S., B.M.P.), University of Iowa
M Bridget Zimmerman - Department of Biostatistics, College of Public Health (M.B.Z.), University of Iowa
Andrew A Pieper - Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH (A.A.P.)
Anil K Chauhan - From the Department of Internal Medicine, Carver College of Medicine (N.D., A.K.C.), University of Iowa
Enrique C Leira - Department of Epidemiology, College of Public Health (E.C.L.), University of Iowa
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.51(6), pp.1855-1861
DOI: 10.1161/STROKEAHA.120.029405
PMID: 32397935
PMCID: PMC7263385
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
Grant note: I01 BX002444 / BLRD VA R21 NS104579 / NINDS NIH HHS
Language: English
Date published: 06/2020
Academic Unit: Neurology; Electrical and Computer Engineering; Psychiatry; Iowa Technology Institute; Biostatistics; Injury Prevention Research Center; Roy J. Carver Department of Biomedical Engineering; Radiology; Civil and Environmental Engineering; Occupational and Environmental Health; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Industrial and Systems Engineering; Public Policy Center (Archive); Neurosurgery; Internal Medicine
Record Identifier: 9984070361502771

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