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Targeting myocardial ischaemic injury in the absence of reperfusion

Authors
  • Basalay, M. V.1
  • Yellon, D. M.1
  • Davidson, S. M.1
  • 1 The Hatter Cardiovascular Institute, 67 Chenies Mews, London, WC1E 6HX, UK , London (United Kingdom)
Type
Published Article
Journal
Basic Research in Cardiology
Publisher
Springer Berlin Heidelberg
Publication Date
Oct 14, 2020
Volume
115
Issue
6
Identifiers
DOI: 10.1007/s00395-020-00825-9
Source
Springer Nature
Keywords
License
Green

Abstract

Sudden myocardial ischaemia causes an acute coronary syndrome. In the case of ST-elevation myocardial infarction (STEMI), this is usually caused by the acute rupture of atherosclerotic plaque and obstruction of a coronary artery. Timely restoration of blood flow can reduce infarct size, but ischaemic regions of myocardium remain in up to two-thirds of patients due to microvascular obstruction (MVO). Experimentally, cardioprotective strategies can limit infarct size, but these are primarily intended to target reperfusion injury. Here, we address the question of whether it is possible to specifically prevent ischaemic injury, for example in models of chronic coronary artery occlusion. Two main types of intervention are identified: those that preserve ATP levels by reducing myocardial oxygen consumption, (e.g. hypothermia; cardiac unloading; a reduction in heart rate or contractility; or ischaemic preconditioning), and those that increase myocardial oxygen/blood supply (e.g. collateral vessel dilation). An important consideration in these studies is the method used to assess infarct size, which is not straightforward in the absence of reperfusion. After several hours, most of the ischaemic area is likely to become infarcted, unless it is supplied by pre-formed collateral vessels. Therefore, therapies that stimulate the formation of new collaterals can potentially limit injury during subsequent exposure to ischaemia. After a prolonged period of ischaemia, the heart undergoes a remodelling process. Interventions, such as those targeting inflammation, may prevent adverse remodelling. Finally, harnessing of the endogenous process of myocardial regeneration has the potential to restore cardiomyocytes lost during infarction.

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