Contents I. Introduction
Cyclic AMP (cAMP) is a key 2nd messenger in signaling pathways that regulate heart rate and cardiac contractility. Alterations in cAMP-mediated signaling have been reported in many cardiac pathologies [1]. The activity and expression of the cAMP-catalyzing enzyme phosphodiesterase-4 (PDE4) are regulated by intracellular cAMP levels [2]. Stereoisomers of the selective PDE4 inhibitor rolipram, high-affinity rolipram and low-affinity -rolipram, have been labeled with [3] and used with PET to measure PDE4 density (and, indirectly, cAMP signaling) in the brain [4]–[8]. However, use of rolipram and rolipram to measure PDE4 density in the heart has not been fully investigated. Previous studies with14C_ or 3H-Iabelled rolipram have revealed the presence of labeled metabolites in the plasma of various species [9] but there have been no reports to date on the presence of labeled metabolites in cardiac tissue. The objective of this study was to determine which of four compartment models (if any) describe the kinetics of rolipram and rolipram in normal dog hearts.
