THE ROLE OF PHOSPHODIESTERASE INHIBITORS IN HEART-FAILURE

Myocardial contractility is dependent on available intracellular calci um and this can be enhanced by increasing intracellular cyclic adenosi ne monophosphate. One way of achieving this is by inhibiting the phosp hodiesterase III enzyme. Over the last 15 years, a number of new drugs with this mechanism of action have been studied in man and have been found not only to have a positive inotropic action on the heart but al so a vasodilating action on peripheral blood vessels. This combination of effects produces favourable haemodynamic improvement in patients w ith chronic heart failure. While some smaller studies showed that this did translate into an improvement in symptoms and functional capacity , a large well-designed and controlled clinical trial showed that surv ival was decreased when milrinone was used in target daily doses of 40 mg. For this reason, chronic long-term oral therapy with phosphodiest erase Ill inhibitors is not currently being actively pursued. They may still have a role as acute short-term therapy in severely ill patient s who do not respond adequately to optimal standard drug therapy. Milr inone has been one of the most widely studied drugs in this regard. Ev en during short-term administration, its use should be closely monitor ed for any evidence of an increase in ventricular arrhythmias or decre ase in ventricular function.