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KEY POINTS

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  • Typical chemical-induced disturbances in cardiac function consist of effects on heart rate (chronotropic), contractility (inotropic), conductivity (dromotropic), and/or excitability (bathmotropic).

  • Cardiomyopathy includes morphologic and functional alterations induced by toxic exposure, leading to decreased cardiac output and peripheral tissue hypoperfusion.

  • Concentric cardiac hypertrophy is an increased size of cardiac myocytes in which new contractile-protein units are assembled in parallel, resulting in a relative increase in the width of individual cardiac myocytes.

  • Eccentric cardiac hypertrophy is an increased size of cardiac myocytes in which new contractile-protein units are assembled in series, resulting in a relatively greater increase in the length than in the width of individual myocytes.

  • Heart failure is the inability of the heart to maintain cardiac output sufficient to meet the metabolic and oxygen demands of peripheral tissues, including changes in systolic and diastolic function that reflect specific alterations in ventricular function and abnormalities in a variety of subcellular processes.

  • Acute cardiac toxicity occurs after a single exposure to a high dose of cardiotoxic chemicals and may be manifested by arrhythmia and can involve apoptosis.

  • Chronic cardiac toxicity, which results from long-term exposure to chemicals, is often manifested by cardiac hypertrophy and the transition to heart failure.

  • Any xenobiotic that disrupts ion movement or homeostasis may induce a cardiotoxic reaction composed principally of disturbances in heart rhythm.

  • All toxicants absorbed into the circulatory system contact vascular cells before reaching other sites in the body.

  • Common mechanisms of vascular toxicity include (1) alterations in membrane structure and function, (2) redox stress, (3) vessel-specific bioactivation of protoxicants, and (4) preferential accumulation of the active toxin in vascular cells.

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INTRODUCTION

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Cardiovascular toxicology is concerned with the adverse effects of extrinsic and intrinsic stresses on the heart and vascular system. Extrinsic stress involves exposure to therapeutic drugs, natural products, and environmental toxicants. Intrinsic stress refers to exposure to toxic metabolites derived from nontoxic compounds such as those found in food additives and supplements. The intrinsic exposures also include secondary neurohormonal disturbance such as overproduction of inflammatory cytokines derived from pressure overload of the heart and counter-regulatory responses to hypertension. These toxic exposures result in alterations in biochemical pathways, defects in cellular structure and function, and pathogenesis of the affected cardiovascular system.

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This chapter is divided into two parts: the heart and the vascular system. The manifestations of toxicologic response of the heart include cardiac arrhythmia, hypertrophy, and overt heart failure. The responses of the vascular system include changes in blood pressure and lesions in blood vessels in the form of atherosclerosis, hemorrhage, and edema.

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OVERVIEW OF THE HEART

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Overview of Cardiac Structural and Physiologic Features

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The main purpose of the heart is to pump blood to the lungs and the systemic arteries so as to provide oxygen and nutrients to all body tissues. Figure 18–1 illustrates the basic anatomy of the heart.

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