HIGH-INTENSITY, LOW-FREQUENCY CATHETER-DELIVERED ULTRASOUND DISSOLUTION OF OCCLUSIVE CORONARY-ARTERY THROMBI - AN IN-VITRO AND IN-VIVO STUDY

Objectives. This study assessed the efficacy of a new high intensity, low frequency therapeutic coronary ultrasound catheter for thrombus dissolution in vitro and in vivo in canine coronary arteries. Background. Therapeutic ultrasound has been shown to dissolve thrombi in vitro and in peripheral arteries in vivo. There have been no previous studies on in vivo coronary thrombus dissolution by ultrasound. Methods. In vitro, we exposed 1- to 4-h old human blood clots for 3 min to pulsed-wave ultrasound. Clot dissolution under various conditions was evaluated. In vivo occlusive coronary thrombi were induced in 18 dogs. Results. In vitro irrigation alone (10 ml/min of normal saline solution) and ultrasound alone each contributed to a reduction of clot weight by 47.1 +/- 11.4 mg and 84.6 +/- 25.6 mg, respectively, after 3 min (p < 0.001). Ultrasound plus irrigation resulted in a reduction of clot weight by 216.5 +/- 31.5 mg after 3 min (p < 0.001). The magnitude of clot dissolution was considerably amplified when ultrasound energy was combined with irrigation, probably because of cavitational effects. In vivo, in three dogs mechanical passage of the unactivated probe failed to recanalize the artery, and the arteries remained thrombotically occluded. After passage of the activated ultrasound probe, angiography revealed widely patent coronary arteries in 13 of 15 dogs and partial recanalization with filling defects indicative of residual thrombus in 2 of 15 dogs. Three of 15 coronary arteries were histologically free of residual thrombi. Mural thrombi extending to less than or equal to 10% of the vessel circumference were seen in 10 of 15 dogs. Residual thrombi greater than or equal to 50% of the vessel circumference were found in two cases. There was no histologic evidence of ultrasound-mediated vessel damage. Conclusions. Catheter-delivered therapeutic ultrasound effectively dissolves clots in vitro and in canine coronary arteries in vivo. Thus, therapeutic catheter delivered ultrasound has the potential to serve as an adjunct or alternative treatment for thrombus-mediated coronary ischemic syndromes or myocardial infarction.