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Transcutaneous Therapeutic Ultrasound Reduces Infarct Size in a Rabbit Model of Acute Insoluble Ischemic Stroke

Rene Flores, John D. Lowery, Robert D. Skinner, Paula K. Roberson, Sean D. Woods and William C. Culp

Low-frequency ultrasound (US) enhances muscle and myocardial perfusion without lysis of the arterial obstruc-tion. We evaluated transcutaneous therapeutic ultrasound with tissue plasminogen activator (tPA) for decreas-es in cerebral infarct volume in rabbits with insoluble arterial occlusions. We hypothesized that US with tPA is effective at reducing infarcts without lysis of the arterial obstruction. New Zealand White rabbits (n=26; 5.2±0.08 kg) received angiography and three 700 to 900 μm embolic spheres were injected into the internal carotid artery occluding its branches. Treatment groups: control (n=10; embolized only), tPA alone (n=7), and tPA+US (n=9). Rabbits receiving US received pulsed-wave US (1-MHz, 0.8 W/cm2) over 1 hour. Rabbits administered tPA re-ceived intravenous tPA (0.9 mg/kg) over 1 hour. Rabbits were sacrificed 24 hours later and infarct volume was determined following staining with triphenyltetrazolium chloride. Immediate collateral flow was determined with digital subtraction angiography. Percent infarct volume was greater (P=0.035) for control (3.4±1.0%) than for tPA+US (0.9±1.0%) rabbits. Rabbits treated with tPA alone (2.0±1.1%) were intermediate and did not differ (P>0.29) from control and tPA+US rabbits. Collateral flow did not (P=0.93) influence infarct volume. Treatment with tPA+US decreases brain infarct volume in rabbits with permanent arterial occlusions, supporting flow stu-dies in muscle or myocardium.