Cardiovascular toxicity

Cardiovascular toxicity
Cardiac Structure
The cardiovascular system consists of the myocardium and vascular vessels which supply the tissues and cells of the body with appropriate nutrients, respiratory gases, hormones, and metabolites and remove the waste products of tissue. In addition to the maintaining of the optimal internal homeostasis of the body as well as for critical regulation of body temperature and maintenance of tissue and cellular pH.
Cardiac myocytes are composed of contractile elements known as myofibrils, which consist of a number of thick and thin myofilaments. The thick filaments consist of the protein myosin, whereas the thin filaments primarily consist of the protein actin. Cardiac myocytes are joined end to end by intercalated disks. Within those disks, there are tight gap junctions that facilitate action potential propagation and intercellular communication.
Cardiac Electrophysiology
Action Potential
The ionic movement of action potential can be classified into 4 phases:


Phase 0: a phase of rapid depolarization due to a fast inflow of Na+ into the cells.
Phase 1: a short initial period of rapid repolarization caused mainly by outflow of K+ from the cells.
Phase 2: a period of delay in repolarization caused by inflow of Ca+2 into the cells.
Phase 3: a second period of rapid repolarization caused mainly by outflow of K+ from the cell .
Phase 4: It’s a fully repolarized state during which Na+ and Ca+2 move out of the cell while K+ move back into the cell

Electrical Conduction in the Heart
Spontaneous depolarization can be found in the sinoatrial (SA) node, the atrioventricular (AV) node, the bundle of His (atrioventricular bundle), and Purkinje fibers. SA nodal cells set the pace of the heart. If the SA node is damaged or inhibited, the next fastest depolarizing cells (AV node) assume the pacemaking activity. The dense fibrous tissue of the AV node causes the electrical impulse to slow down. This delayed transfer of current between the atria and the ventricles allows the atria to complete contraction before depolarization of the ventricles.
Electrical cardiac activity is regulated by the autonomic nervous system (ANS). Norepinephrine and similar sympathomimetics stimulate an increase in cardiac rate and the contractility of the myocardium. The major effect of parasympathomimetics is to decrease the rate of depolarization with only a slight decrease in ventricular contractility.
Excitation-Contraction Coupling
For contraction to occur, both ATP and Ca2 + must be available. Mechanical contraction of cardiac myocytes occurs when Ca2 + binds to the protein troponin C with tropomysin. After a Ca2 +-induced conformational change in troponin C and tropomysin, ATP is hydrolyzed, and subsequently allowing myosin to bind actin, thus producing contraction.



Cardiac Output
Abnormal Heart Rhythm
Ischemic Heart Disease
Cardiac Hypertrophy and Heart Failure
Cardiomyopathies
General Mechanisms of Cardiotoxicity
Cardiotoxicants:
Vascular system toxicity