Therapeutic Ultrasound Improves Myocardial Blood Flow and Reduces Infarct Size in a Canine Model of Coronary Microthromboembolism

Mrinal Yadava, D. Elizabeth Le, Igor V. Dykan, Marjorie R. Grafe, Matthew Nugent, Azzdine Y. Ammi, David Giraud, Yan Zhao, Jessica Minnier, Sanjiv Kaul

Research output: Contribution to journalArticle

Abstract

Background: Therapeutic ultrasound (TUS) has been used to lyse infarct-related coronary artery thrombus. There has been no study examining the effect of TUS specifically on myocardial microthromboemboli seen in acute myocardial infarction and acute coronary syndromes. The aim of this study was to test the hypothesis that TUS improves myocardial blood flow (MBF) and reduces infarct size (IS) in this situation by dissolving myocardial microthrombi. Methods: An open-chest canine model of myocardial microthromboembolism was created by disrupting a thrombus in the left anterior descending coronary artery, and 1.05- and 0.25-MHz TUS (n = 7 each) delivered epicardially for 30 min was compared with control (n = 6). MBF and IS (as a percentage of left anterior descending coronary artery perfusion bed size) were measured 60 min after treatment. In addition, immunohistochemistry was performed to assess microthrombi, and histopathology was performed to define inflammation. Results: Transmural, epicardial, and endocardial myocardial blood volume and MBF (measured using myocardial contrast echocardiography) and percentage wall thickening were significantly higher 60 min after receiving TUS compared with control. The ratio of IS to left anterior descending coronary artery perfusion bed size was significantly smaller (P = .03) in the 1.05-MHz TUS group (0.14 ± 0.04) compared with the control (0.31 ± 0.06, P = .04) and 0.25-MHz (0.36 ± 0.08) groups. MBF versus percentage wall thickening exhibited a linear relation (r = 0.65) in the control and 1.05-MHz TUS groups but not in the 0.25-MHz TUS group (r = 0.29). The presence of myocardial microemboli in vessels >10 μm in diameter was significantly reduced in the 1.05-MHz TUS group compared with the other two groups. The distribution and intensity of inflammation was higher in the 0.25-MHz TUS group compared with the other groups. Conclusions: TUS at 1.05 MHz is effective in restoring myocardial blood volume and MBF, thus reducing IS by clearing the microcirculation of microthrombi. IS reduction is not seen at 0.25 MHz, despite improvement in MBF, which may be related to the increased inflammation noted at this frequency. Because both acute myocardial infarction and acute coronary syndromes are associated with microthromboembolism, these results suggest that TUS could have a potential adjunctive role in the treatment of both conditions.

Original languageEnglish (US)
JournalJournal of the American Society of Echocardiography
DOIs
StateAccepted/In press - Jan 1 2019

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Canidae
Coronary Vessels
Therapeutics
Hospital Bed Capacity
Acute Coronary Syndrome
Inflammation
Blood Volume
Thrombosis
Perfusion
Myocardial Infarction
Therapeutic Uses
Microcirculation
Echocardiography
Thorax
Immunohistochemistry

Keywords

  • Coronary thrombosis
  • Infarct size
  • Microthrombi
  • Therapeutic ultrasound

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Therapeutic Ultrasound Improves Myocardial Blood Flow and Reduces Infarct Size in a Canine Model of Coronary Microthromboembolism. / Yadava, Mrinal; Le, D. Elizabeth; Dykan, Igor V.; Grafe, Marjorie R.; Nugent, Matthew; Ammi, Azzdine Y.; Giraud, David; Zhao, Yan; Minnier, Jessica; Kaul, Sanjiv.

In: Journal of the American Society of Echocardiography, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Therapeutic ultrasound (TUS) has been used to lyse infarct-related coronary artery thrombus. There has been no study examining the effect of TUS specifically on myocardial microthromboemboli seen in acute myocardial infarction and acute coronary syndromes. The aim of this study was to test the hypothesis that TUS improves myocardial blood flow (MBF) and reduces infarct size (IS) in this situation by dissolving myocardial microthrombi. Methods: An open-chest canine model of myocardial microthromboembolism was created by disrupting a thrombus in the left anterior descending coronary artery, and 1.05- and 0.25-MHz TUS (n = 7 each) delivered epicardially for 30 min was compared with control (n = 6). MBF and IS (as a percentage of left anterior descending coronary artery perfusion bed size) were measured 60 min after treatment. In addition, immunohistochemistry was performed to assess microthrombi, and histopathology was performed to define inflammation. Results: Transmural, epicardial, and endocardial myocardial blood volume and MBF (measured using myocardial contrast echocardiography) and percentage wall thickening were significantly higher 60 min after receiving TUS compared with control. The ratio of IS to left anterior descending coronary artery perfusion bed size was significantly smaller (P = .03) in the 1.05-MHz TUS group (0.14 ± 0.04) compared with the control (0.31 ± 0.06, P = .04) and 0.25-MHz (0.36 ± 0.08) groups. MBF versus percentage wall thickening exhibited a linear relation (r = 0.65) in the control and 1.05-MHz TUS groups but not in the 0.25-MHz TUS group (r = 0.29). The presence of myocardial microemboli in vessels >10 μm in diameter was significantly reduced in the 1.05-MHz TUS group compared with the other two groups. The distribution and intensity of inflammation was higher in the 0.25-MHz TUS group compared with the other groups. Conclusions: TUS at 1.05 MHz is effective in restoring myocardial blood volume and MBF, thus reducing IS by clearing the microcirculation of microthrombi. IS reduction is not seen at 0.25 MHz, despite improvement in MBF, which may be related to the increased inflammation noted at this frequency. Because both acute myocardial infarction and acute coronary syndromes are associated with microthromboembolism, these results suggest that TUS could have a potential adjunctive role in the treatment of both conditions.",
keywords = "Coronary thrombosis, Infarct size, Microthrombi, Therapeutic ultrasound",
author = "Mrinal Yadava and Le, {D. Elizabeth} and Dykan, {Igor V.} and Grafe, {Marjorie R.} and Matthew Nugent and Ammi, {Azzdine Y.} and David Giraud and Yan Zhao and Jessica Minnier and Sanjiv Kaul",
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AU - Yadava, Mrinal

AU - Le, D. Elizabeth

AU - Dykan, Igor V.

AU - Grafe, Marjorie R.

AU - Nugent, Matthew

AU - Ammi, Azzdine Y.

AU - Giraud, David

AU - Zhao, Yan

AU - Minnier, Jessica

AU - Kaul, Sanjiv

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N2 - Background: Therapeutic ultrasound (TUS) has been used to lyse infarct-related coronary artery thrombus. There has been no study examining the effect of TUS specifically on myocardial microthromboemboli seen in acute myocardial infarction and acute coronary syndromes. The aim of this study was to test the hypothesis that TUS improves myocardial blood flow (MBF) and reduces infarct size (IS) in this situation by dissolving myocardial microthrombi. Methods: An open-chest canine model of myocardial microthromboembolism was created by disrupting a thrombus in the left anterior descending coronary artery, and 1.05- and 0.25-MHz TUS (n = 7 each) delivered epicardially for 30 min was compared with control (n = 6). MBF and IS (as a percentage of left anterior descending coronary artery perfusion bed size) were measured 60 min after treatment. In addition, immunohistochemistry was performed to assess microthrombi, and histopathology was performed to define inflammation. Results: Transmural, epicardial, and endocardial myocardial blood volume and MBF (measured using myocardial contrast echocardiography) and percentage wall thickening were significantly higher 60 min after receiving TUS compared with control. The ratio of IS to left anterior descending coronary artery perfusion bed size was significantly smaller (P = .03) in the 1.05-MHz TUS group (0.14 ± 0.04) compared with the control (0.31 ± 0.06, P = .04) and 0.25-MHz (0.36 ± 0.08) groups. MBF versus percentage wall thickening exhibited a linear relation (r = 0.65) in the control and 1.05-MHz TUS groups but not in the 0.25-MHz TUS group (r = 0.29). The presence of myocardial microemboli in vessels >10 μm in diameter was significantly reduced in the 1.05-MHz TUS group compared with the other two groups. The distribution and intensity of inflammation was higher in the 0.25-MHz TUS group compared with the other groups. Conclusions: TUS at 1.05 MHz is effective in restoring myocardial blood volume and MBF, thus reducing IS by clearing the microcirculation of microthrombi. IS reduction is not seen at 0.25 MHz, despite improvement in MBF, which may be related to the increased inflammation noted at this frequency. Because both acute myocardial infarction and acute coronary syndromes are associated with microthromboembolism, these results suggest that TUS could have a potential adjunctive role in the treatment of both conditions.

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KW - Infarct size

KW - Microthrombi

KW - Therapeutic ultrasound

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