Targeting myocardial ischaemic injury in the absence of reperfusion
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REVIEW
Targeting myocardial ischaemic injury in the absence of reperfusion M. V. Basalay1 · D. M. Yellon1 · S. M. Davidson1 Received: 13 July 2020 / Accepted: 28 September 2020 © The Author(s) 2020
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. Keywords Ischaemia · Heart · Cardioprotection · Animals · Infarction · Remodelling · Regeneration
Introduction An acute coronary syndrome results in a sudden reduction of blood flow to the myocardium. In the case of STelevation myocardial infarction (STEMI), this is usually caused by the acute rupture of atherosclerotic plaque and thrombotic obstruction of a coronary artery. Non-STEMI (NSTEMI) may be precipitated by coronary artery spasm or other factors that restrict blood flow. Reperfusion therapy, with the aim of rapidly returning blood flow to the ischaemic myocardium, has been a key advance in the treatment of STEMI. If blood flow in the culprit coronary artery is not promptly restored, the obstruction inevitably leads to myocardial death. The size of myocardial infarction (MI) is known to be a major determinant of prognosis in these patients (reviewed in [56]). Timely restoration of blood flow * S. M. Davidson [email protected] 1
The Hatter Cardiovascular Institute, 67 Chenies Mews, London WC1E 6HX, UK
in the culprit coronary artery(s) is able to reduce infarct size (IS) in patient
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