Ultrasound-assisted thrombolysis with streptokinase improves thrombus resolution with minimal distal embolisation

Abstract

Catheter-directed ultrasound (US) has a synergistic effect on thrombus with streptokinase (SK). We aimed to assess whether a new method of arterial thrombolysis based on a combination of short-term US and intravenous SK administration can improve efficacy and minimize distal embolisation as compared to these two interventions applied separately. Experiments have been done on 23 mongrel dogs with ligature-induced femoral thrombosis divided into groups treated with (i) enzymatic thrombolysis (intravenous SK, n=6), (ii) 36kHz US-assisted thrombolysis (n=6), (iii) US+SK applied together (n=6), and (iv) control group with no treatment (n=5). US intensity at the distal end of the waveguide was 10-15W/cm(2). Selective angiography, plethysmography and sphygmography have been used to assess thrombus resolution and distal embolisation. US-assisted thrombolysis alone was associated with good thrombus resolution, but substantial distal embolisation. SK-induced fibrinolysis alone did not provoke distal embolization but showed delayed thrombus resolution compared to US-treated group. Dual US+SK therapy resulted in high rate of US destruction without significant Under the combined US+SK action, nearly additive summation of US cavitation and SK effects as well as synergistic effects of both these factors on hemostasis parameters (activated partial thromboplastin, prothrombin, and thrombin time; fibrinogen, FDP, D-dimers, antithrombin III, plasminogen, and α2-antiplasmin) have been observed. Combination of CK and US-induced thrombolysis shows high efficacy with minimal distal embolisation. Arterial thrombus destruction by the combination of gradual (40min) SK intravenous administration followed by short-time (1.5min) intense US exposure improves shows positive effect of parameters of haemostasis. The magnitude and clinical significance of possible adverse effects of the dual fibrinolytic intervention related to endothelial injury and risk of bleeding needs to be further assessed in longer-term experiments and appropriately designed clinical trials.