Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No-Reflow in Canine Models by Sonothrombolysis

Crit Care Med. 2018 Sep;46(9):e912-e920. doi: 10.1097/CCM.0000000000003255.

Abstract

Objectives: Effective treatment for microvascular thrombosis-induced coronary no-reflow remains an unmet clinical need. This study sought to evaluate whether diagnostic ultrasound and microbubbles treatment could improve outcomes of coronary no-reflow by dissolving platelet- and erythrocyte-rich microthrombi.

Design: Randomized controlled laboratory investigation.

Setting: Research laboratory.

Subjects: Mongrel dogs.

Interventions: Coronary no-reflow models induced by platelet- or erythrocyte-rich microthrombi were established and randomly assigned to control, ultrasound, recombinant tissue-type plasminogen activator, ultrasound + microbubbles, or ultrasound + microbubbles + recombinant tissue-type plasminogen activator group. All treatments lasted for 30 minutes.

Measurements and main results: Percentage of microemboli-obstructed coronary arterioles was lower in ultrasound + microbubbles group than that in control group for platelet- (> 50% obstruction: 10.20% ± 3.56% vs 31.80% ± 3.96%; < 50% obstruction: 14.80% ± 4.15% vs 28.20% ± 3.56%) and erythrocyte-rich microthrombi (> 50% obstruction: 8.20% ± 3.11% vs 30.60% ± 4.83%; < 50% obstruction: 12.80% ± 4.15% vs 25.80% ± 3.70%) (p < 0.001). Percentage change of myocardial blood flow in left anterior descending artery-dominated region, left ventricular ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles group than that in control group for both types of microthrombi (p < 0.001). Percentage change of myocardial blood flow, ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles and ultrasound + microbubbles + recombinant tissue-type plasminogen activator groups than that in recombinant tissue-type plasminogen activator group for platelet-rich microthrombi (p < 0.05).

Conclusions: Ultrasound + microbubbles treatment could dissolve platelet- and erythrocyte-rich microthrombi, thereby improving outcomes of coronary no-reflow, making it a promising supplement to current reperfusion therapy for acute ST-segment elevation myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Thrombosis / diagnostic imaging*
  • Coronary Thrombosis / therapy*
  • Disease Models, Animal
  • Dogs
  • Microbubbles / therapeutic use*
  • Random Allocation
  • Thrombolytic Therapy / methods*
  • Treatment Outcome
  • Ultrasonography