ABSTRACT
Heart failure is the leading cause of death and debilitating conditions in industrialized countries. Congenital heart anomaly, valve dysfunction, coronary artery disease, hypertension, myocarditis, metabolic disorder, and idiopathic cardiomyopathy are known to deteriorate to heart failure. Although the mechanism of heart failure differs among the underlying heart diseases, there are common features of heart failure. Heart failure is characterized by impairment of the contractile function of cardiac muscle. The pump function of cardiac muscle is determined by the number of functional cardiomyocytes and the contactility of each cardiomyocyte. When approximately 40% of contractile mass of the left ventricle is lost by acute myocardial infarction, the remaining left ventricular muscle cannot compensate for reduced cardiac performance, leading to heart failure. Cardiomyocyte contractility is determined by the velocity and the strength of contraction and relaxation of myofilaments. A number of factors are involved in this regulation and most of them are dependent on energy. Cross-bridge cycling between actin and myosin consumes the largest part of energy for cardiomyocyte contraction. Regulation of cytosolic Ca
level is also important in generating contractility of myofilaments. The intracellular Ca
level in each contraction and relaxation cycle is mainly regulated by Ca
-ATPases present in the sarcoplasmic reticulum and the sarcolemma. Thus, energy deprivation of cardiac myocytes directly affects contractile function. Depletion of myocardial high energy phosphates occurs as a result of deficient production of ATP by mitochondria or excess utilization of energy by ATPases. Therefore, stimulating ATP synthesis by mitochondria represents a promising approach for treatment of patients with heart failure.
