Ultrasound enhances novel thrombolysis technique
MedWire News: Doppler ultrasound treatment enhances the thrombolytic effect of echogenic liposomes (ELIP) loaded with tissue plasminogen activator (tPA), resulting in earlier and more complete recanalization rates, US study findings indicate.
Susan Laing (University of Texas Health Science Center, Houston) and colleagues have previously shown, in vitro, that ELIP can act not only as an ultrasound contrast agent, but also as an agent for ultrasound-releasable directed thrombolytic therapy.
In the present study, the researchers evaluated the thrombolytic effect of tPA-loaded ELIP with and without pulsed ultrasound treatment in a rabbit model of thrombosis.
Following thrombi generation with a solution of sodium ricinoleate plus thrombin added to the abdominal aorta, groups of four rabbits were randomly assigned to receive tPA-loaded ELIP (200 µg of tPA plus 5 mg of lipid) or empty ELIP (5 mg of lipid) with or without pulsed color Doppler ultrasound (5.7 MHz) treatment for 2 minutes. Ultrasound treatment was initiated once the tPA-loaded ELIP were visualized within the abdominal aorta.
Laing and co-authors report that tPA-loaded ELIP highlighted thrombi in the abdominal aortas significantly more effectively than empty ELIP, with approximate mean gray scale values of 51 versus 32, respectively.
No thrombolysis was observed in the animals treated with empty ELIP or empty ELIP with ultrasound. However, treatment of the thrombi with tPA-loaded ELIP resulted in recanalization of the abdominal aorta, as demonstrated by improvement in blood flow in the distal aorta.
Pulsed ultrasound treatment further enhanced the thrombolytic effect of tPA-loaded ELIP, resulting in earlier and more complete recanalization rates. Indeed, 15 minutes after treatment there was 100% blood flow recovery in the group that received tPA-loaded ELIP plus ultrasound, compared with 58% in the group that received tPA-loaded ELIP without ultrsound.
"This study demonstrates the potential of a novel thrombolytic technique, combining a targeted thrombolytic-loaded contrast agent and ultrasound application, to enhance thrombolysis, with clinical applications for acute thrombotic processes," Laing et al conclude in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.
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By Laura Dean