ABSTRACT
Cardiac toxicology is concerned with the adverse effects of exposure to extrinsic and intrinsic toxic substances in the heart. The measurement of cardiac toxic effects ranges from morphological changes to molecular alterations. These measurements are based on the anatomy, physiology, and biochemistry of the heart. Toxic substances can cause adverse effects but at the same time also cause myocardial protective responses. The cardiomyocytes in the heart respond individually to the same insult, and the same insult may have different effects on the population of cardiomyocytes, depending on the location of the cells in the heart; for example, cells localized in endocardium would respond differently from cells localized in the epicardium. The measurement of cardiac toxic effects requires taking the sum of all different responses of individual cardiomyocytes and noncardiac cells within the heart. Toxic exposures can result in alterations in biochemical pathways, energy metabolism, cellular structural and function, electrophysiology, and contractility leading to toxicologic cardiomyopathy. The defense mechanisms are also activated at the same time, but the balance between detrimental and protective actions determines the phenotype of the heart under the toxic exposure condition. The manifestations of toxicologic cardiomyopathy include cardiac arrhythmia, hypertrophy, and overt heart failure. The ultimate functional effect of these manifestations is decreased cardiac output and reduced peripheral tissue perfusion. The critical cellular event leading to toxicologic cardiomyopathy is myocardial cell death. Recognition
during the last decade of the role of apoptosis in the development of heart failure significantly enhanced our knowledge of cardiac toxicology.
