New opportunities of using an ischemic cascade blocker in the therapy of acute myocardial infarction

Abstract

Oxidative stress plays a special role in acute coronary syndrome (ACS), in particular, is a leading link in the pathogenesis of reperfusion myocardial damage. The products of free radical oxi­dation can trigger the death of cardiomyocytes and are responsible for 50 % of the final size of the necrosis area in ACS, the occurrence of reperfusion arrhythmia, systolic and microvascular dysfunction. Therefore, adequate antioxidant therapy aimed at elimina­ting reac­tive oxygen species, activating antioxidants, modulating the processes of immediate and delayed cell death should be an important component of the management of patients with ACS. Edaravone is the most promising antioxidant and an ischemic cascade blocker due to its pharmacokinetic and pharmacodynamic properties. According to several experimental and clinical studies, the use of edaravone in patients with ACS leads to a decrease in the free radicals on the background of activation of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, catalase, to preserve the normal architecture of mitochondria and other cellular structures, to inhibit the expression of various proteins involved in the activation of apoptosis, ferroptosis, and proinflammatory response. At the clinical level, edaravone helps to reduce the area of necrosis with a significant decrease of plasma levels of CPK-MV, prevents the development of arrhythmias and systolic dysfunction on the background of ischemia/reperfusion. According to randomized, placebo-controlled studies, the use of edaravone in patients with ACS before reperfusion in the first 6 hours after the onset of symptoms is effective in reducing infarct area and preventing reperfusion arrhythmias. Thus, edaravone is a powerful antioxidant and an ischemic cascade blocker with additional anti-apoptotic and anti-ferroptotic, antinecrotic, anti-inflammatory effects, stabilizes cardiomyocytes and endothelial cells, and its administration in acute coronary syndrome is a promi­sing strategy for the prevention of reperfusion injury, myocardial and vascular remodeling. Due to its multifaceted effects, edaravone may also be useful in other cardiovascular diseases.

Keywords

• acute coronary syndrome
• edaravone
• antioxidant
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