- 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.
The cardiovascular system has two major components: the myocardium and a diverse network of vascular vessels consisting of arteries, capillaries, and veins. Both components function to supply the tissues and cells of the body with appropriate nutrients, respiratory gases, hormones, and metabolites and to remove the waste products of tissue and cellular metabolism as well as foreign matter such as invading microorganisms. n addition, the cardiovascular system is responsible for maintaining the optimal internal homeostasis of the body as well as for critical regulation of body temperature and maintenance of tissue and cellular pH.
Figure 18–1 illustrates the basic anatomy of the heart. 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.
Diagram illustrating the basic anatomy of the heart.
Review of Cardiac Structure
The structural organization of myocardial tissue is shown in Figure 18–2. The primary contractile unit is the cardiac muscle cell, or cardiac myocyte. Cardiac myocytes are composed of contractile elements known as myofibrils, which consist of a number of thick and thin myofilaments. The thick filaments are special assemblies of the protein myosin, whereas the thin filaments are primarily the protein actin. Cardiac myocytes are joined end-to-end by intercalated disks where there are tight gap junctions that facilitate action potential propagation and intercellular communication.
Structural organization of cardiac muscle tissue.
The heart contains cardiac myocytes, which contribute the majority of cardiac mass. Cardiac fibroblasts, vascular cells, Purkinje cells, and other connective tissue cells make up the majority of cells in the heart. Hypertrophy of remaining cardiac myocytes is a hallmark of cardiac remodeling following myocardial injuries. Cardiac fibroblasts promote fibrosis and scarring of injured cardiac tissue. The heart is vulnerable to injury because of the limited proliferative capacity of cardiac myocytes, and promotion of cardiac fibroblast proliferation and cardiac remodeling following injury.
The characteristic appearance of the cardiac action potential demonstrates how ion currents result in changes in membrane potential (Figure 18–3). In a resting cell, the density of the electrical charge on ...