University of Oulu

Tuomas Anttila, Johanna Herajärvi, Henna Laaksonen, Caius Mustonen, Hannu-Pekka Honkanen, Elitsa Y. Dimova, Jarkko Piuhola, Peppi Koivunen, Tatu Juvonen & Vesa Anttila (2023) Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction: study on a porcine model, Scandinavian Cardiovascular Journal, 57:1, DOI:

Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction : study on a porcine model

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Author: Anttila, Tuomas1; Herajärvi, Johanna1; Laaksonen, Henna1;
Organizations: 1Research Unit of Surgery, Anesthesia and Intensive Care, Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
2Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
3Department of Cardiology, Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland
4Department of Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
5Heart Center, Turku University Hospital, University of Turku, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Informa, 2023
Publish Date: 2023-10-23


Objectives: Remote ischemic preconditioning (RIPC) mitigates acute myocardial infarction (AMI). We hypothesized that RIPC reduces the size and severity of AMI and explored molecular mechanisms behind this phenomenon.

Design: In two series of experiments, piglets underwent 60 min of the circumflex coronary artery occlusion, resulting in AMI. Piglets were randomly assigned into the RIPC groups (n = 7 + 7) and the control groups (n = 7 + 7). The RIPC groups underwent four 5-min hind limb ischemia-reperfusion cycles before AMI. In series I, the protective efficacy of RIPC was investigated by using biomarkers and echocardiography with a follow-up of 24 h. In series II, the heart of each piglet was harvested for TTC-staining to measure infarct size. Muscle biopsies were collected from the hind limb to explore molecular mechanisms of RIPC using qPCR and Western blot analysis.

Results: The levels of CK-MBm (p = 0.032) and TnI (p = 0.007) were lower in the RIPC group. Left ventricular ejection fraction in the RIPC group was greater at the end of the follow-up. The myocardial infarct size in the RIPC group was smaller (p = 0.033). Western blot indicated HIF1α stabilization in the skeletal muscle of the RIPC group. PCR analyses showed upregulation of the HIF target mRNAs for glucose transporter (GLUT1), glucose transporter 4 (GLUT4), phosphofructokinase 1 (PFK1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase 1 (ENO1), lactate dehydrogenase (LDHA) and endothelial nitric oxidate synthase (eNOS). Conclusions. Biochemical, physiologic, and histologic evidence confirms that RIPC decreases the size of AMI. The HIF pathway is likely involved in the mechanism of the RIPC.

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Series: Scandinavian cardiovascular journal
ISSN: 1401-7431
ISSN-E: 1651-2006
ISSN-L: 1401-7431
Volume: 57
Issue: 1
Article number: 2251730
DOI: 10.1080/14017431.2023.2251730
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: This work was supported by The Finnish Foundation for Cardiovascular Research (Vesa Anttila), The Sigrid Jusélius Foundation, The Emil Aaltonen Foundation, and The Jane and Aatos Erkko Foundation (Peppi Koivunen).
Copyright information: ß2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.