Cargando…

Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging

OBJECTIVE: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphoh...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Ziqian, Chen, Wei, Zhang, Ruzhi, Wang, Lei, Chen, Ridong, Zheng, Jie, Gao, Fabao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Radiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231619/
https://www.ncbi.nlm.nih.gov/pubmed/32410404
http://dx.doi.org/10.3348/kjr.2019.0853
_version_ 1783535219876298752
author Xu, Ziqian
Chen, Wei
Zhang, Ruzhi
Wang, Lei
Chen, Ridong
Zheng, Jie
Gao, Fabao
author_facet Xu, Ziqian
Chen, Wei
Zhang, Ruzhi
Wang, Lei
Chen, Ridong
Zheng, Jie
Gao, Fabao
author_sort Xu, Ziqian
collection PubMed
description OBJECTIVE: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). MATERIALS AND METHODS: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. RESULTS: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = −0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). CONCLUSION: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.
format Online
Article
Text
id pubmed-7231619
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Korean Society of Radiology
record_format MEDLINE/PubMed
spelling pubmed-72316192020-06-01 Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging Xu, Ziqian Chen, Wei Zhang, Ruzhi Wang, Lei Chen, Ridong Zheng, Jie Gao, Fabao Korean J Radiol Cardiovascular Imaging OBJECTIVE: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). MATERIALS AND METHODS: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. RESULTS: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = −0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). CONCLUSION: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI. The Korean Society of Radiology 2020-06 2020-04-06 /pmc/articles/PMC7231619/ /pubmed/32410404 http://dx.doi.org/10.3348/kjr.2019.0853 Text en Copyright © 2020 The Korean Society of Radiology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cardiovascular Imaging
Xu, Ziqian
Chen, Wei
Zhang, Ruzhi
Wang, Lei
Chen, Ridong
Zheng, Jie
Gao, Fabao
Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title_full Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title_fullStr Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title_full_unstemmed Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title_short Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging
title_sort human recombinant apyrase therapy protects against myocardial ischemia/reperfusion injury and preserves left ventricular systolic function in rats, as evaluated by 7t cardiovascular magnetic resonance imaging
topic Cardiovascular Imaging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231619/
https://www.ncbi.nlm.nih.gov/pubmed/32410404
http://dx.doi.org/10.3348/kjr.2019.0853
work_keys_str_mv AT xuziqian humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT chenwei humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT zhangruzhi humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT wanglei humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT chenridong humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT zhengjie humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging
AT gaofabao humanrecombinantapyrasetherapyprotectsagainstmyocardialischemiareperfusioninjuryandpreservesleftventricularsystolicfunctioninratsasevaluatedby7tcardiovascularmagneticresonanceimaging