Low-Frequency Vibrations Enhance Thrombolytic Therapy and Improve Stroke Outcomes

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 mm3; 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 mm3; 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 mm3; 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.