Microvascular leakage in acute myocardial infarction

Characterization by histology, biochemistry, and magnetic resonance imaging

Xiao Ming Gao, Qi-Zhu Wu, Helen Kiriazis, Yidan Su, Li Ping Han, James Todd Pearson, Andrew J. Taylor, Xiao-Jun Du

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepenta-acetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24–48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology. NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

Original languageEnglish
Pages (from-to)H1068-H1075
Number of pages8
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume312
Issue number5
DOIs
Publication statusPublished - 15 May 2017

Keywords

  • Cardiac magnetic resonance
  • Infarct size
  • Microvascular damage
  • Microvascular leakage
  • Myocardial infarction

Cite this

@article{ceca0e54512040de99a724653e3213a5,
title = "Microvascular leakage in acute myocardial infarction: Characterization by histology, biochemistry, and magnetic resonance imaging",
abstract = "Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepenta-acetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24–48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2{\%}) was greater than that of infarct (47 ± 4{\%}, P < 0.01) or MVO (36 ± 4{\%}, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology. NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.",
keywords = "Cardiac magnetic resonance, Infarct size, Microvascular damage, Microvascular leakage, Myocardial infarction",
author = "Gao, {Xiao Ming} and Qi-Zhu Wu and Helen Kiriazis and Yidan Su and Han, {Li Ping} and Pearson, {James Todd} and Taylor, {Andrew J.} and Xiao-Jun Du",
year = "2017",
month = "5",
day = "15",
doi = "10.1152/ajpheart.00073.2017",
language = "English",
volume = "312",
pages = "H1068--H1075",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
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}

Microvascular leakage in acute myocardial infarction : Characterization by histology, biochemistry, and magnetic resonance imaging. / Gao, Xiao Ming; Wu, Qi-Zhu; Kiriazis, Helen; Su, Yidan; Han, Li Ping; Pearson, James Todd; Taylor, Andrew J.; Du, Xiao-Jun.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 312, No. 5, 15.05.2017, p. H1068-H1075.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Microvascular leakage in acute myocardial infarction

T2 - Characterization by histology, biochemistry, and magnetic resonance imaging

AU - Gao, Xiao Ming

AU - Wu, Qi-Zhu

AU - Kiriazis, Helen

AU - Su, Yidan

AU - Han, Li Ping

AU - Pearson, James Todd

AU - Taylor, Andrew J.

AU - Du, Xiao-Jun

PY - 2017/5/15

Y1 - 2017/5/15

N2 - Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepenta-acetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24–48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology. NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

AB - Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepenta-acetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24–48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology. NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

KW - Cardiac magnetic resonance

KW - Infarct size

KW - Microvascular damage

KW - Microvascular leakage

KW - Myocardial infarction

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M3 - Article

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JF - American Journal of Physiology - Heart and Circulatory Physiology

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