Excitation-contraction Coupling in the Heart and the Negative Inotropic Action of Volatile Anesthetics

IN a comprehensive review in 1987, Rusy and Komai discussed the possible mechanisms by which volatile anesthetics inhibit cardiac contraction. Since that time, there have been advancements in the understanding of excitation-contraction coupling, cardiac mechanics, and the actions of volatile anesthetics. There are essentially three major factors that determine the force of contraction of heart muscle cells: the magnitude of cytosolic Ca increase after electrical excitation, the responsiveness of the contractile proteins to Ca , and the sarcomere length (SL) at which the contractile proteins are activated. Hence, there are two possible ultimate direct negative inotropic actions of volatile anesthetics: a reduction in Ca availability or a decrease in the Ca responsiveness (Ca -sensitivity or maximal Ca -activated force) of the contractile apparatus. The rate of relaxation of the muscle cells, on the other hand, depends on the rate at which Ca is cleared from the cytosol, which facilitates its dissociation from the regulatory proteins of the contractile system. The control of calcium cycling and the activity of the contractile proteins consume energy that must be continuously supplied by the mitochondria, another potential site volatile of anesthetic action.