Subcellular Remodeling and Cardiac Dysfunction Due to Ischemia–Reperfusion Injury

Ischemic heart disease as a consequence of the blockade of coronary flow is associated with dramatic changes in cardiac function, metabolism, and ultrastructure. A wide variety of subcellular defects have been observed in ischemic and ischemia–reperfusion (I/R) hearts. There is evidence that various subcellular organelles become remodeled during the development of I/R injury and oxidative stress may be intimately involved in producing these abnormalities. In view of the direct participation of the sarcoplasmic reticulum (SR) and myofibrils in heart function, it appears that cardiac contraction and relaxation abnormalities in ischemic heart disease are due to remodeling of the SR and myofibrils, whereas remodeling of the sarcolemma membrane may determine the extent of intracellular Ca2+ overload, subsequent proteolysis, and irreversible injury to the heart. Furthermore, the acute effects of I/R injury on cardiac function are thought to be due to changes in the activities of subcellular organelles as a consequence of functional group modification, whereas the chronic effects of I/R yielding delayed recovery of cardiac function may be the consequence of changes in cardiac gene expression and subcellular remodeling. Although female hearts are less susceptible to I/R injury, in comparison to males, the basis for this gender difference in cardiac ischemic injury and protection needs to be defined. As females lose their resistance to different cardiovascular diseases after menopause, it appears that gender differences in cardiac susceptibility to I/R injury may be mediated through the participation of ovarian hormones. On the other hand, it is possible that the male sex hormone, testosterone, exacerbates I/R-induced cardiac dysfunction in adult males. Notably, in comparison to males, there is very little information in the literature on subcellular remodeling or on the mechanisms which regulate cardiac function during the development of I/R injury in female hearts.