ABSTRACT
The heart is the muscular pump responsible for the nutritional and functional blood supply to the pulmonary and systemic circuits and is, therefore, responsible for survival of all tissues. The effects of circulating xenobiotics can be manifested as both structural and functional changes in the heart and blood vessels in a wide variety of organs and tissues. Alterations that cause minimal effects in cardiac function can be associated with severe pathologies in another organ such as the brain or kidney because adequate blood ow is required for maintenance of normal organ function. Xenobiotics can cause functional disturbances, such as cardiac arrhythmias, that may result in severe signs, including sudden death syndrome, that are not associated with marked structural damage to the heart. Additionally, in human patients, silent, occult preexisting cardiac disease may increase the likelihood of developing cardiomyopathy from cardiotoxicity. Alterations in hepatic and renal blood ow can profoundly affect the metabolism and clearance of the xenobiotic, which can alter endothelial cell (EC) structure and function leading to severe vascular compromise. In the heart, in addition to functional disturbances, the response to xenobiotic exposure can include developmental abnormalities and structural abnormalities. The range of structural abnormalities includes hypertrophy, various types of degeneration and/or necrosis, brosis, subsequent repair and development of cardiomyopathy, and heart failure.
