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Myocardial infarction (MI) - more commonly referred to as a heart attack - is an acute event caused by the interruption of blood supply to regions of the heart, leading to myocardial necrosis. Infarction of a substantial area of the myocardium can disrupt normal conductance of the heart, leading to cardiac arrest.
In the majority of cases, an MI is immediately preceded by the presence of an occlusive thrombus within a coronary artery, blocking blood flow to the downstream tissue. The most common cause of an occlusive thrombus within a coronary artery is the rupture of an atherosclerotic plaque. However, the occlusion of a coronary artery may also result from coronary embolism. This can occur in patients following stent placement, angioplasty, and coronary artery bypass grafting.
One of the few warning symptoms for MI is the occurrence of angina pectoris - a severe chest pain which may also radiate down the left arm. Angina is caused by a lack of oxygen to the myocardium due to coronary artery obstruction or spasm, and can be classified as either 'unstable' or 'stable' angina. Patients with stable angina experience 'predictable' chest pain during exertion which resolves following rest or the administration of the NO donor, nitroglycerin. There is little damage to the myocardium during stable angina. However, an episode of unstable angina - that is, chest pain which occurs at rest or in patients with no history of stable angina - may induce myocardial necrosis, albeit at a reduced level to that observed during acute MI. The most common blood biomarkers used to diagnose acute MI or unstable angina are cardiac troponins T (cTnT) and I (cTnI), two components of cardiac muscle whose serum levels rise as a result of myocardial necrosis.
Immediate pharmacological treatment of angina is achieved by the administration of nitric oxide donors, but longer term therapy involves either increasing blood supply to the heart using vasodilators such as calcium channel blockers, or by reducing metabolic demand of the heart. This can be achieved through decreasing heart rate by administering β-blockers. A further pharmacological mechanism for preventing angina is to increase ATP production whilst maintaining the same oxygen consumption. This can be brought about by inhibiting the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT1), or by altering fatty acid oxidation to increase metabolic efficiency.
Following an infarction, damaged myocardium cannot regenerate and so is replaced by non-contractile scar tissue. This alters both the contractility and the conductance of the myocardium and may subsequently lead to the development of an arrhythmia or heart failure. The injection of multipotent cardiac stem cells to the infarcted area of the heart following a myocardial infarction has shown promise in facilitating regeneration of damaged myocardium, but their availability is limited. As a result, research efforts are currently focused on producing cardiomyocytes by differentiating more readily available stem cell populations, such as undifferentiated skeletal myoblasts or bone marrow-derived adult stem cells.
Inducing cardiomyogenic function in these stem cell populations has been achieved using a range of methods. These include cardiac preconditioning, whereby stem cells are differentiated in media previously used to culture primary cardiomyocytes; and also by using small molecule inhibitors that modulate stem cell signaling pathways including the Wnt/β-catenin pathway. Facilitating the repair and regeneration of damaged myocardium following infarction, together with preventing aberrant remodeling, represent promising future therapeutic avenues within the field of myocardial infarction research.