Role of cyclic AMP in myocardial cell function.

A series of agents which stimulate the formation of cyclic AMP are well-known positive inotropic agents in the heart. This fact has suggested that cyclic AMP may indeed mediate the positive inotropic effects. The elucidation of precise in vivo mechanisms utilizing in vitro and isolated techniques is always difficult; in the myocardial cell, a very complicated and multicompartmented cell, all such in vivo-in vitro correlation must be viewed with caution. In this review, the authors has attempted to list possible cellular sites of inotropic intervention based on current concepts of excitation contraction coupling (which also are speculative). Recent evidence from in vitro experiments have suggested several sites which are apparently affected by cyclic AMP-mediated events and which are thought to be intimately related to the control of myocardial contraction. It is suggested that the myocardium be viewed as a multicompartmented system with several effector sites for cyclic AMP-mediated events, all of which have individual controls; this type of thesis would be necessary to explain the volume of experimental data which fails to show simple correlation between myocardial cyclic AMP levels and cardiac contractility. The difficulties in designing experiments to further elucidate these mechanisms and the possibility of "linked enzyme systems" are also discussed.