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

Konijnenberg, LSF, Luiken, TTJ, Veltien, A, Uthman, L, Kuster, CTA, Rodwell, L, de Waard, GA, Kea-te Lindert, M, Akiva, A, Thijssen, DHJ, Nijveldt, R and van Royen, N (2023) Imatinib attenuates reperfusion injury in a rat model of acute myocardial infarction. Basic Research in Cardiology, 118 (1). ISSN 0300-8428

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Open Access URL: https://doi.org/10.1007/s00395-022-00974-z (Published version)


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.

Item Type: Article
Uncontrolled Keywords: Myocardium; Heart; Animals; Rats; Rats, Wistar; Myocardial Reperfusion Injury; Myocardial Infarction; Myocardial Reperfusion; Male; Imatinib Mesylate; Acute myocardial infarction; Cardiac magnetic resonance imaging; Langendorff; Microvascular injury; Reperfusion injury; Rats; Male; Animals; Imatinib Mesylate; Rats, Wistar; Myocardial Infarction; Heart; Myocardium; Myocardial Reperfusion Injury; Myocardial Reperfusion; 1102 Cardiorespiratory Medicine and Haematology; Cardiovascular System & Hematology
Subjects: R Medicine > R Medicine (General)
Divisions: Sport & Exercise Sciences
Publisher: Springer
SWORD Depositor: A Symplectic
Date Deposited: 02 Mar 2023 12:39
Last Modified: 02 Mar 2023 12:45
DOI or ID number: 10.1007/s00395-022-00974-z
URI: https://researchonline.ljmu.ac.uk/id/eprint/19004
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