ABSTRACT
Cardiotoxic effects may be broadly categorized as (1) functional changes that may or may not be accompanied by histopathological change, and (2) structural injury with or without functional change. Serious functional disturbances may occur without any structural alterations. For example, electrophysiological effects of drugs are typically mediated by their direct interaction with cardiac ion channels, which are involved in the transmission of cardiac impulses as action potentials that ensure normal cardiac function. Perturbations of these ion channels can lead to a prolongation of cardiac QT interval and/or to an arrhythmia and a myocardial event such as Torsades de Pointe, which is a variant of ventricular tachycardia that has distinct characteristics on the electrocardiogram. However, in these events, there typically is no obvious loss of structural integrity or release of cellular constituents into the plasma. Adverse functional effects may occur secondarily, due to excessive neuroendocrine alterations or chronically increased cardiac workload that overwhelms the heart’s adaptive capacity and leads to failure. Degenerative structural effects that release intracellular constituents are mediated by direct myocardial toxic injury. These events may arise from adverse subcellular effects such as on mitochondria, calcium homeostasis, membrane permeability, and redox status.
