3:09 PM Abstract No. 176 Effect of acoustic pulses on fibrin structure in clots

The EkoSonic Endovascular System has been used to clear blood clots in patients with pulmonary embolism, deep vein thrombosis or peripheral arterial occlusions by applying ultrasound (US) in combination with lytic drugs. It is believed that clots exposed to acoustic pulses undergo structural changes in the fibrin network. To better understand this US effect, changes to fibrinogen and plasma clots treated with US were investigated using clot turbidity measurements and scanning electron microscopy (SEM) images. EkoSonic research catheters were built with single sandwich transducers with resonant frequencies around 2.3 MHz. Clots were prepared from factor XIII (FXIII)–depleted fibrinogen, regular fibrinogen and human plasma. Clot turbidity was monitored by measuring optical density (OD) at λ = 340 nm using a microplate spectrophotometer until a maximum OD was reached (approximating complete clot formation), and then further measured following US treatment to identify differences between US-treated and untreated clots. Fibrin fiber structural changes were visualized using a scanning electron microscope and quantified by evaluating fiber diameter from SEM images. Following 15 minutes of US exposure, the turbidity of all fibrinogen and plasma clots were reduced. FXIII-depleted fibrinogen clots showed a significant decrease in turbidity between US- and non-US treated clots (-28% vs. -1.9%). Fibrinogen and plasma clots exposed to US resulted in a similar reduction in OD compared to control clots. SEM images of FXIII-depleted fibrinogen clots indicated a significant decrease (P < 0.05) in fibrin fiber diameter with US (33.8 ± 17.2 nm) vs. without US (63.4 ± 24.0 nm). In addition, delivery of tissue plasminogen activator (tPA) into clots in the presence of US was investigated and resulted in enhanced lysis relative to controls. This study shows US-induced fibrin thinning in multiple clot models. This may be associated with increased availability of binding sites on fibrin for lytic drug binding thereby enhancing the thrombolysis effect when clots are exposed to US.