Ischemia/Reperfusion Injury following Acute Myocardial Infarction: A Critical Issue for Clinicians and Forensic Pathologists

Abstract

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI.

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

“…2) Ischemia reperfusion injury, in which the outbreak of ROS plays an important role, not only causes irreversible myocardial necrosis but also induces cardiomyocyte apoptosis. 3) ROS can be direct cytotoxicity or may pose potential risk of cell death by transforming into free radicals that react with macromolecules, DNA, proteins and lipids.…”

“…1) Although restoration of blood flow to the ischemic heart tissues is important, it is not adequate because myocardial ischemic damage is progressively developed following reperfusion due to an over-production of a large number of biospecies. 2,3) Compelling evidence demonstrated that free radicals generated during ischemia and reperfusion play pivotal roles in myocardial apoptosis. Free radical scavengers can effectively inhibit myocardial apoptosis.…”

Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation‐induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2

“…Tenzymatic activity of ALDH2 was determined by detecting the transformation from NAD + to NADH, as described. 2 After collecting and quantifying protein, 50 μg of total protein was added to 33 mmol/L sodium pyrophosphate buffer (pH 9.5) containing 0.8 mmol/L of NAD + and 15 μmol/L of propionaldehyde at 25°C. ALDH2 activity was measured in 33 mmol/L sodium pyrophosphate, and 0.1 mL proteins extract.…”

“…The recovery of blood flow after ischaemia exacerbates tissue and organ injuries, which is known as ischaemia/reperfusion (I/R) injury . Myocardial I/R injury is a complicated pathophysiological phenomenon commonly appeared after ischaemia heart surgery and heart disease .…”

Protective effects of fisetin against myocardial ischemia/reperfusion injury

“…An estimated 3.8 million men and 3.4 million women die from CHD every year (1)(2)(3). Myocardial ischemia/reperfusion injury is a severe pathological change associated with CHD, which leads to a reduction in heart ejection fraction and causes cardiac decompensation (4). Inhibition of apoptosis to prevent myocardial ischemia/reperfusion injury has long been a therapeutic target (5).…”