Effect of Clot Aging and Cholesterol Content on Ultrasound-Assisted Thrombolysis

Abstract

Exposure to 2-MHz transcranial diagnostic ultrasound enhances the thrombolytic activity of intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (sonothrombolysis). However, rates of arterial recanalization vary widely, depending upon the clot burden, its location, and stroke subtype. We evaluated the influence of age and cholesterol level of the blood clots on sonothrombolysis in an in vitro model. To "age" the clots, serum was replaced by fresh blood periodically. We increased the cholesterol content of the clots by adding cholesterin to the blood. The clots were lysed by tPA and/or transcranial Doppler ultrasound sonication for 1 h. The extent of thrombolysis induced by various treatment protocols (controls, sonication, tPA, and sonothrombolysis) was evaluated with relative changes in the clot weights and in the clot structure by scanning electron microscopy (SEM) at end of the experiment. Sonothrombolysis induced significantly higher weight reduction in fresh clots (37.3 % in 2-h old clots versus 24.8 % in 10-h ones, p < 0.005) as well as the clots with higher cholesterol levels (41.7 versus 30.6 % in normal cholesterol clots, p < 0.005). SEM demonstrated patterns of clot dissolution among various treatment modalities. Sonothrombolysis induced better clot lysis in fresh thrombi with high cholesterol levels.

A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia

“…EPA normally exists in extremely low levels in the brain but can be dramatically elevated after long-term FO supplement [18]. To facilitate the translation of n-3 PUFA treatment for clinical use, future studies should take into consideration the confounding effects from aging and stroke comorbidities [63–65], and also test the therapeutic efficacy in models involving tPA thrombolysis [66–69]. …”

Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis

“…Many studies have shown that the thrombolytic effects of MBs or thrombolytic drugs were varied with different types or ages of thrombi. 1,2 To verify whether the thrombolytic effects of M-MBs would vary with different thrombi, we applied red and white thrombi and two ages of thrombi to research in this study. Since the time window for thrombolytic treatment of acute myocardial infarction is within 12 hours, we used 12-hour clots as older thrombi to investigate the efficacy of sonothrombol-ysis.…”

Sonothrombolysis in Acute Ischemic Stroke: Current Status

“…Recently, our group studied the effects of sonothrom-bolysis in an in-vitro experiment. 12 Blood clots were prepared from horse blood and used to create occlusions in the silicone tubing, mimicking the intracranial arteries, in an in-vitro water tank with controlled temperature. We evaluated the relationship between sonothrombolysis and age of the clot as well as the cholesterol content.…”