Selective updates on mechanisms of action of positive inotropic agents

Several extensive reviews concerning the actions of new positive inotropic agents in the treatment of congestive heart failure, often with reference to their mechanism of action, have recently been published. Each of them has presented specific points of view. This review will place special emphasis on the significance of intracellular sodium activity for the modulation of myocardial inotropy; the continuing importance, after a 200 year history, of the use of cardiac glycosides as strong inotropic agents; the emerging significance of the phosphoinositide (PIP2) pathway to provide additional second messengers for the modulation and regulation of cardiac inotropy; the contribution of the alpha 1-adrenergic system to cardiac inotropy; the increasing awareness of the significant involvement of adenosine and its antagonists in cardiac function; and the increasing realization that myocardial tissues are not homogeneous, i.e., that in many species the atrial and ventricular tissues are using different, even opposite mechanisms in the generation of their functional responses.