Abstract 5503: Sonothrombolysis in a Rabbit Model of Acute Insoluble Ischemic Stroke

Introduction: Evidence suggests that low-frequency ultrasound (US) improves tissue perfusion in the rabbit ischemic limb and enhances myocardial perfusion even without removing the arterial obstruction. We evaluated US-facilitated thrombolysis, or sonothrombolysis, with microbubbles (MB) and tissue plasminogen activator (tPA) for decreases in infarct volume in rabbits with insoluble middle cerebral artery (MCA) occlusions. Hypothesis: Sonothrombolysis with MB or tPA is effective at reducing infarcts without lysis of arterial obstruction. Methods: New Zealand White rabbits (n = 34; 5.2±0.07 kg) received angiography and three embolic spheres (diameter = 700 to 900 μ m) were injected into the internal carotid artery occluding the MCA. Rabbits were randomly assigned to one of four groups. Control (n = 10) rabbits were embolized but received no US, tPA, or MB. Other groups were tPA (n = 7) without US, tPA+US (n = 9), and MB+US (n = 8). Treatment was initiated one hour following angiographic verification of occlusion. Rabbits with US received pulsed wave US (1 MHz at 0.8 W/cm 2 ) for 1 hour and rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Rabbits with MB received intravenous MB (0.16 mg/kg) over 30 minutes. Rabbits were sacrificed at 24 hours and infarct volume was determined using vital stains on brain sections. Results: Percent infarct volume averaged 3.4±0.9%, 2.0±1.1%, 1.8±1.0%, and 0.92±0.9% for control, tPA, MB+US, and tPA+US rabbits, respectively; infarct volume tended (P = 0.066) to be decreased for rabbits treated with tPA+US compared to controls. Infarct volume did not differ (P > 0.26) between controls and rabbits treated with tPA and MB+US. Conclusions: Combined treatment with tPA and US shows a trend towards decreasing brain infarct volume in rabbits with permanent MCA occlusion, but not to the extent found in muscle or myocardium at lower frequencies.