Typical chemical-induced disturbances in cardiac function consist of effects on heart rate (chronotropic), contractility (inotropic), conductivity (dromotropic), and/or excitability (bathmotropic).
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.
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, plus secondary neurohormonal disturbances such as overproduction of inflammatory cytokines derived from pressure overload of the heart and counter-regulatory responses to hypertension or uremic toxins that arise from renal failure. The manifestations of toxicological 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.
Overview of Cardiac Structural and Physiological Features
Cardiac muscle is one of the excitable tissues of the body. It shares many bioelectrical properties with other excitable tissues, and also has unique features associated with cardiac structural and physiological specificities. Figure 18–1 illustrates the basic anatomy of the heart.
Diagram illustrating the basic anatomy of the heart.
Review of Cardiac Structure
Is the Cardiac myocytes are composed of several major structural features and organelles, as illustrated in Fig. 18–2. The contractile element, the myofibril, consists of smaller filaments (the thick and thin myofilaments). The thick filaments are special assemblies of the protein myosin, while thin filaments are made up primarily of the protein actin. Cardiac myosin is a hexamer composed of one pair of myosin heavy chains (MHCs) and two pairs of myosin light chains (MLCs). Two isoforms of MHC, α and β, are expressed in cardiac muscle. Similarly, two isoforms of actin are expressed in the heart (cardiac and skeletal α-actin).
Structural organization of cardiac muscle tissue.
Under electron microscopy, these myocardial contractile proteins display alternating dark bands (A bands, predominantly composed of myosin) and light bands (I bands, predominantly composed of actin). Visible in the middle of the I band is a dense vertical Z line. The area between two Z lines is called a ...