A review of myocardial ischaemia/reperfusion injury: Pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment

Abstract

Cardiovascular diseases are known to be the most fatal diseases worldwide. Ischaemia/reperfusion (I/R) injury is at the centre of the pathology of the most common cardiovascular diseases. According to the World Health Organization estimates, ischaemic heart disease is the leading global cause of death, causing more than 9 million deaths in 2016. After cardiovascular events, thrombolysis, percutaneous transluminal coronary angioplasty or coronary bypass surgery are applied as treatment. However, after restoring coronary blood flow, myocardial I/R injury may occur. It is known that this damage occurs due to many pathophysiological mechanisms, especially increasing reactive oxygen types. Besides causing cardiomyocyte death through multiple mechanisms, it may be an important reason for affecting other cell types such as platelets, fibroblasts, endothelial and smooth muscle cells and immune cells. Also, polymorphonuclear leukocytes are associated with myocardial I/R damage during reperfusion. This damage may be insufficient in patients with co‐morbidity, as it is demonstrated that it can be prevented by various endogenous antioxidant systems. In this context, the resulting data suggest that optimal cardioprotection may require a combination of additional or synergistic multi‐target treatments. In this review, we discussed the pathophysiology, experimental models, biomarkers, treatment and its relationship with genetics in myocardial I/R injury. Significance of the study This review summarized current information on myocardial ischaemia/reperfusion injury (pathophysiology, experimental models, biomarkers, genetics and pharmacological therapy) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system and pharmacology.

Cardioprotection via Metabolism for Rat Heart Preservation Using the High-Pressure Gaseous Mixture of Carbon Monoxide and Oxygen

“…Ischemia–reperfusion injury is at the center of the pathology of the most common cardiovascular diseases and can affect mitochondrial function. Mitochondrial dysfunction mostly affects myocardial contractility but also predisposes one to arrhythmias due to the myocardium having high metabolic demand and mitochondrial content [ 20 , 21 ]. Although no major changes were observed in the myocardial structure at pretransplantation among the three groups ( Figure 2 a), after transplantation, erythrodiapedes was observed between some muscle fibers in the myocardium of the CS groups, whereas the myocardium of the HPG group was almost normal in structure ( Figure 1 b).…”

SUMOylation as a Therapeutic Target for Myocardial Infarction

“…Myocardial ischemia is caused by a decrease in coronary blood flow or failure to meet the demand of cardiac tissue for oxygen. Ischemia indicates that the environment oxygen is not enough to maintain the oxidative phosphorylation in the mitochondria ( 60 ). During ischemia, anaerobic glycolysis of glucose produces excessive lactic acid in the ischemic cells and ultimately causes acidification in the heart ( 61 ).…”

Dynamic Regulation of Cysteine Oxidation and Phosphorylation in Myocardial Ischemia–Reperfusion Injury

“…While hypoxia stimulates several cell survival responses, prolonged oxygen limitation can initiate cell death pathways [ 7 ]. Myocardial ischemia is characterized by periods of ATP depletion, pH changes, and calcium dysregulation [ 3 ].…”

“…Ischemia is induced by either a thrombotic or spastic occlusion of the coronary arteries, which feed the heart, and leads to a series of pathological changes that culminate in the death of cardiomyocytes [ 2 ]. Subsequent reperfusion—the restoration of blood flow—exacerbates cell death by introducing reactive oxygen species (ROS), which damage macromolecules, such as DNA, proteins, and lipids [ 3 ]. Each insult further impedes heart function, ultimately resulting in heart failure and patient death.…”