Overview of cardiovascular physiologic and pharmacologic aspects of selective phosphodiesterase peak III inhibitors.

In recent years several agents have been developed as selective inhibitors of the low Michaelis constant cyclic adenosine monophosphate (cAMP) phosphodiesterase (peak III), a fraction of the cyclic nucleotide phosphodiesterases that is specific for the metabolic breakdown of cAMP. These agents are often referred to as PDE III inhibitors and share similar pharmacologic profiles. The principal interest in these agents--the therapy of congestive heart failure--is based on the cardiovascular effects that result from sequential elevation of intracellular cAMP, cAMP-dependent protein kinase activation, phosphorylation of cellular proteins and change in cellular function. The selective PDE III inhibitors have a triad of cardiovascular activities that provide hemodynamic benefit to patients with congestive heart failure. As a representative drug from this class of compounds, milrinone increases myocardial contractility, increases the rate of ventricular relaxation, and unloads the heart by way of a peripheral vasodilator action. The selective PDE III inhibitors offer a new modality for oral therapy of congestive heart failure.