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

Circulation. 2000 May 2;101(17):2026-9. doi: 10.1161/01.cir.101.17.2026.

Abstract

Background: Limitations of coronary thrombolysis include the time to reperfusion, patency rate, and bleeding. We evaluated the use of noninvasive transcutaneous 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 coronary angiography. After >/=60 minutes of occlusion, tissue-type plasminogen activator (t-PA; 1.42 mg/kg) was given intravenously over 90 minutes. A total of 12 of the 24 dogs had concomitant transcutaneous application of low-frequency ultrasound (27 kHz) over the chest. At 90 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, mean 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 confirmed 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-frequency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombolysis, (2) seems safe, and (3) has substantial potential as a noninvasive adjunct to improve coronary patency without increasing the risk of bleeding.

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Coronary Angiography
  • Coronary Circulation
  • Coronary Thrombosis / therapy*
  • Coronary Vessels / pathology
  • Disease Models, Animal
  • Dogs
  • Fibrinolytic Agents / therapeutic use
  • Myocardial Infarction / therapy*
  • Thrombolytic Therapy*
  • Tissue Plasminogen Activator / therapeutic use
  • Ultrasonic Therapy*

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator