Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes. Issue 6 (June 2020)

• Record Type: Journal Article
• Authors: Dhanesha, Nirav; Schnell, Thomas; Rahmatalla, Salam; DeShaw, Jonathan; Thedens, Daniel; Parker, Bradley M.; Zimmerman, M. Bridget; Pieper, Andrew A.; Chauhan, Anil K.; Leira, Enrique C.
• Is Part Of: Stroke. Volume 51:Issue 6(2020)
• Publication Date: 2020-06
• Subjects: air ambulance -- murine models -- stroke -- thrombolytic therapy -- vibration; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.120.029405
• Languages: English
• ISSNs: 0039-2499

Abstract

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 3 ; P =0.007) and increased favorable neurological outcomes (86% versus 28%; P =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 3 ; P =0.58) nor improved neurological outcomes (37% versus 28%; P =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; P =0.81) or neurological outcomes (25% versus 11%; P =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 3 ; P =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. Abstract : Supplemental Digital Content is available in the text.