Therapeutic potential of cyclic nucleotide phosphodiesterase inhibitors inheart failure

There are several reasons to believe that agents that augment cAMP-mediated signalling in cardiac myocytes should have beneficial effects in patients with heart failure. However, clinical trials of first-generation cyclic nuc leotide phosphodiesterase (PDE3) inhibitors, which raise cAMP content by bl ocking its hydrolysis, have shown that chronic administration of these drug s affect survival adversely. The problem may be the non-selective activatio n of a broad spectrum of cAMP-regulated cellular responses these agents eli cit. More selective (or alternatively selective) cyclic nucleotide PDE inhi bitors might improve results by evoking a more restricted set of cellular r esponses.