Targeting myocardial ischaemic injury in the absence of reperfusion

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.

RETRACTED: Overexpression of SERCA2a Alleviates Cardiac Microvascular Ischemic Injury by Suppressing Mfn2-Mediated ER/Mitochondrial Calcium Tethering

“…Although researchers have revealed many mechanisms underlying ischemic injury ( Gao et al, 2019 ; Bankapalli et al, 2020 ), the roles of calcium overload and subsequent oxidative stress in myocardial infarction injury are still far from clear ( Basalay et al, 2020 ; Cao et al, 2020a ). SERCA2a, the main factor involved in calcium handling, is an ATP-driven protein that transports Ca 2+ back to the ER ( Pinton et al, 2008 ).…”

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway

“…Measurements of the myocardial area at risk (AAR), area at infarct (AAI), and area at NR (AAN) were performed according to a previous report ( Basalay et al, 2020 ; Chen et al, 2020 ). In brief, 4% thioflavin S 1 ml/kg was injected from the femoral vein, and 2% Evans blue 2 ml/kg was injected from the inferior vena cava.…”

Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia‐Reperfusion Injury

“…From the perspective of treatment, timely restoration of blood flow to the myocardium is an effective way to relieve tissue ischemia and insufficient nutrient supply [ 45 , 46 ]. Interestingly, however, reperfusion of ischemic tissue can cause additional damage due to I/R injury [ 47 , 48 ]. This concept was first proposed in 1955 by Sewell et al, based on observations made in dogs after coronary artery ligation [ 49 ].…”