RELATIONSHIP BETWEEN INOTROPIC ACTIVITY AND PHOSPHODIESTERASE INHIBITION FOR FLOSEQUINAN AND MILRINONE

The goal of this study was to assess the relationship between the posi tive inotropic response to high concentrations of the vasodilators flo sequinan and BTS 53 554 (the sulfone metabolite of flosequinan) and th e effect of both compounds on different forms of cyclic nucleotide pho sphodiesterase. In addition, the relationship between inotropic activi ty and phosphodiesterase inhibition for the cardiotonic milrinone was also evaluated. All three agents exerted a positive inotropic effect o n human cardiac muscle fibers. The concentration of milrinone required to increase cardiac contractility was comparable to the concentration required to inhibit the milrinone-sensitive subclass of cyclic AMP-sp ecific phosphodiesterase (type III phosphodiesterase). However, no suc h relationship was observed for flosequinan and BTS 53 554. These resu lts suggest that the cardiac response to high concentrations of floseq uinan and BTS 53 554 is not mediated by inhibition of type III phospho diesterase.