Calcium Overload and Cardiac Function.

The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca2+ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca2+ overload include arrhythmias caused by oscillatory (Vos) and non-oscillatory (Vex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na+ in electrical abnormalities as a charge carrier in the Na+-Ca2+ exchange and a role of Ca2+ in mechanical toxicity. Ca2+ overload may be induced by an increase in [Na+]i through the inhibition of the Na+-K+ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca2+ load (e.g. catecholamines). The Ca2+ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca2+ overload than myocardial fibers, possibly because of their greater Na+ load. If the SR is predominantly Ca2+ overloaded, Vos and fast discharge are induced through an oscillatory release of Ca2+ in diastole from the SR; if the cytoplasm is Ca2+ overloaded, the non-oscillatory Vex tail is induced at negative potentials. The decrease in contractile force by Ca2+ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents Ios and Iex underlie Vos and Vex, respectively, both being due to an electrogenic extrusion of Ca2+ through the Na+-Ca2+ exchange. Ios is an oscillatory current due to an oscillatory release of Ca2+ in early diastole from the Ca2+-overloaded SR, and Iex is a non-oscillatory current due to the extrusion of Ca2+ from the Ca2+-overloaded cytoplasm. Ios and Iex can be present singly or simultaneously. An increase in [Ca2+]i appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca2+]i may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca2+-overloaded cardiac cells by decreasing the inhibition of the Na+-K+ pump by Ca2+, thereby leading to a reduction in Ca2+ overload and to an increase in force of contraction. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]