Unfortunately, while preservation of a viable (but at-risk) heart can improve both short-and long-term outcomes, reperfusion is not an unalloyed blessing. Indeed, late restoration of blood flow into ischemic tissues can incite greater local damage than might otherwise have occurred— so-called “reperfusion injury”.
The factors that contribute to reperfusion injury include the following:
Mitochondrial dysfunction. Ischemia alters the mitochondrial membrane permeability, which allows proteins to move into the mitochondria. This leads to swelling and rupture of the outer membrane, releasing mitochondrial contents that promote apoptosis.
Myocyte hypercontracture. During periods of ischemia, the intracellular levels of calcium are increased as a result of impaired calcium cycling and sarcolemmal damage. After reperfusion, the contraction of myofibrils is augmented and uncontrolled, causing cytoskeletal damage and cell death.
Free radicals, including superoxide anion (•O− 2 ), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), nitric oxide–derived peroxynitrite, and hydroxyl radicals (•OH). These are produced within minutes of reperfusion and cause damage to the myocytes by altering membrane proteins and phospholipids.
Leukocyte aggregation may occlude the microvasculature and contribute to the “no-reflow” phenomenon. Further, leukocytes elaborate proteases and elastases that cause cell death.
Platelet and complement activation also contribute to microvascular injury. Complement activation is thought to play a role in the no-reflow phenomenon by injuring the endothelium.
The typical appearance of reperfused myocardium in the setting of an acute MI is shown in
Figure 11.12 . Such infarcts are hemorrhagic as a consequence of vascular injury and leakiness. Microscopically, irreversibly damaged myocytes after reperfusion develop contraction band necrosis; in this pathologic process, intense eosinophilic bands of hypercontracted sarcomeres are created by an influx of calcium across plasma membranes that heightens actin-myosin interactions. In the absence of ATP, the sarcomeres cannot relax and get stuck in an agonal tetanic state. Thus, while reperfusion can salvage reversibly injured cells, it also alters the morphology of irreversibly injured cells.
The classic MI is heralded by severe, crushing substernal chest pain (or pressure) that can radiate to the neck, jaw, epigastrium, or left arm. In contrast to angina pectoris, the associated pain typically lasts several minutes to hours, and is not relieved by nitroglycerin or rest. However, in a substantialminorityofpatients(10%to15%),MIspresentwith the atypical signs and symptoms, and may even be entirely asymptomatic. Such “silent” infarcts are particularly common in patients with underlying diabetes mellitus (in which autonomic neuropathy may prevent perception of pain) and in older adults.
The pulse generally is rapid and weak, and patients are often diaphoretic (sweating) and nauseous (particularly with posterior wall MIs). Dyspnea is common, resulting from impaired myocardial contractility and dysfunction of the mitral valve apparatus, with resultant acute pulmonary congestion and edema. With massive MIs (involving more than 40% of the left ventricle), cardiogenic shock develops.
Electrocardiographic abnormalities are important for the diagnosis of MI; these include Q waves, ST segment changes, and T wave inversions (the latter two representing abnormalities in myocardial repolarization). Arrhythmias caused by electrical abnormalities in the ischemic myocardium and conduction system are common; indeed, sudden cardiac death from a lethal arrhythmia accounts for the vast majority of MI-related deaths occurring before hospitalization.