Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysisin a canine model of acute myocardial infarction

Background-Limitations of coronary thrombolysis include the time to reperfu sion, patency rate, and bleeding. We evaluated the use of noninvasive trans cutaneous ultrasound to augment coronary thrombolysis. Methods and Results-In 24 dogs, a thrombotic occlusion of the left anterior descending coronary artery was induced and documented by 12-lead ECG and c oronary angiography. After greater than or equal to 60 minutes of occlusion , tissue-type plasminogen activator (t-PA; 1.42 mg/kg) was given intravenou sly over 90 minutes. A total of 12 of the 24 dogs had concomitant transcuta neous application of low-frequency ultrasound (27 kHz) over the chest. At 9 0 minutes, the mean TIMI grade flow in the t-PA alone group was 0.92+/-1.4 compared with 2.42+/-1.9 in the t-PA plus ultrasound group (P=0.006). TIMI 2 to 3 flow was present in 4 of 12 cases receiving t-PA alone compared with 10 of 12 cases receiving t-PA plus ultrasound (P=0.003). At 180 minutes, m ean TIMI grade flow was 0.75+/-1.4 in the t-PA alone group versus 2.58+/-0. 9 in the t-PA plus ultrasound group (P=0.001). Pathological examination con firmed the angiographic patency rate and did not reveal injury secondary to ultrasound in the skin, soft tissues, heart, or lungs. Conclusions-In vivo, the noninvasive transthoracic application of low-frequ ency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombol ysis, (2) seems safe, and (3) has substantial potential as a noninvasive ad junct to improve coronary patency without increasing the risk of bleeding.