Title: In Vitro Enzymatic Clot Lysis Using Focused Ultrasound Waves as an Adjunct to Thrombolytic Drug Tenecteplase and in Combination with Microbubbles
Abstract: The low and incomplete recanalization performance of thrombolytic therapy in stroke patients has created the need to use focused ultrasound (FUS) energy as a way to enhance thrombolysis efficacy. The aim of the study was to establish an optimized treatment protocol that through nonthermal mechanisms maximizes the thrombolytic activity of thrombolytic drug tenecteplase (TNK-tPA), leading to thrombolysis enhancement. Using an in vitro circulating flow clot model, designed to reproduce the physiologic situations of a middle cerebral artery occlusion occurred either 4 cm deep into a brain tissue or superficially, the role of various experimental parameters on thrombolysis efficacy were evaluated. For this purpose, fully retracted porcine blood clots were treated with FUS waves as an adjunct to thrombolytic TNK-tPA, in the presence or absence of microbubbles (MBs). A spherically FUS transducer (4 cm diameter), focusing at 10 cm and operating at 1.18 MHz, was used. In all the proposed parametric studies, temperature elevation at beam focus never exceeded 1 °C, providing that the contribution of thermal mechanisms to clot lysis was negligible. The effect of experimental parameters such as temperature, FUS alone, TNK-tPA alone and in synergy, sonication time, standing waves, flow rate, acoustic power and MB administration in thrombolysis efficacy was investigated. The degree of thrombolysis achieved by each parameter was measured either as the relative reduction in the mass of the clot or in mg of mass clot removed. Study findings clearly demonstrated that the combination of 1.18 MHz FUS pulses with MBs strongly accelerated the thrombolytic action of TNK-tPA. Experimental results have been very promising, specifically in the case of a superficial occlusion, where 1,050 mg of mass clot was removed after 30 min of treatment. Since stroke is time dependent, this thrombolytic rate should be sufficient for timely recanalization of an occluded cerebral artery.
Publication Year: 2017
Publication Date: 2017-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 1
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