Imatinib attenuates reperfusion injury in a rat model of acute myocardial infarction

Following an acute myocardial infarction, reperfusion of an occluded coronary artery is often accompanied by microvascular injury, leading to worse long-term prognosis. Experimental studies have revealed the potential of tyrosine-kinase inhibitor imatinib to reduce vascular leakage in various organs...

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Bibliographic Details
Published in:	Basic research in cardiology Vol. 118; no. 1; p. 2
Main Authors:	Konijnenberg, Lara S. F., Luiken, Tom T. J., Veltien, Andor, Uthman, Laween, Kuster, Carolien T. A., Rodwell, Laura, de Waard, Guus A., Kea-te Lindert, Mariska, Akiva, Anat, Thijssen, Dick H. J., Nijveldt, Robin, van Royen, Niels
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 13-01-2023 Springer Nature B.V
Subjects:	Animal models Animals Blood pressure Cardiology Coronary artery Diastolic pressure Electron microscopy Fluorescence Heart Heart attacks Imatinib Imatinib Mesylate - pharmacology Injury prevention Ischemia Kinases Leakage Magnetic resonance imaging Male Males Medicine Medicine & Public Health Microvasculature Myocardial infarction Myocardial Infarction - pathology Myocardial Reperfusion Myocardial Reperfusion Injury - pathology Myocardium Myocardium - pathology Original Contribution Placebos Rats Rats, Wistar Reperfusion Tyrosine Langendorff Microvascular injury Acute myocardial infarction Reperfusion injury Cardiac magnetic resonance imaging
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Summary:	Following an acute myocardial infarction, reperfusion of an occluded coronary artery is often accompanied by microvascular injury, leading to worse long-term prognosis. Experimental studies have revealed the potential of tyrosine-kinase inhibitor imatinib to reduce vascular leakage in various organs. Here, we examined the potential of imatinib to attenuate microvascular injury in a rat model of myocardial reperfusion injury. Isolated male Wistar rat hearts ( n = 20) in a Langendorff system and male Wistar rats ( n = 37) in an in vivo model were randomly assigned to imatinib or placebo and subjected to ischaemia and reperfusion. Evans-blue/Thioflavin-S/TTC staining and Cardiac Magnetic Resonance Imaging were performed to assess the extent of reperfusion injury. Subsequently, in vivo hearts were perfused ex vivo with a vascular leakage tracer and fluorescence and electron microscopy were performed. In isolated rat hearts, imatinib reduced global infarct size, improved end-diastolic pressure, and improved rate pressure product recovery compared to placebo. In vivo, imatinib reduced no-reflow and infarct size with no difference between imatinib and placebo for global cardiac function. In addition, imatinib showed lower vascular resistance, higher coronary flow, and less microvascular leakage in the affected myocardium. At the ultrastructural level, imatinib showed higher preserved microvascular integrity compared to placebo. We provide evidence that low-dose imatinib can reduce microvascular injury and accompanying myocardial infarct size in a rat model of acute myocardial infarction. These data warrant future work to examine the potential of imatinib to reduce reperfusion injury in patients with acute myocardial infarction.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1435-1803 0300-8428 1435-1803
DOI:	10.1007/s00395-022-00974-z