THE ROLE OF PHOSPHODIESTERASE INHIBITORS IN HEART-FAILURE

Myocardial contractility is dependent on available intracellular calcium and this can be enhanced by increasing intracellular cyclic adenosine monophosphate. One way of achieving this is by inhibiting the phosphodiesterase 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 also a vasodilating action on peripheral blood vessels. This combination of effects produces favourable haemodynamic improvement in patients with 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 survival was decreased when milrinone was used in target daily doses of 40 mg. For this reason, chronic long-term oral therapy with phosphodiesterase Ill inhibitors is not currently being actively pursued. They may still have a role as acute short-term therapy in severely ill patients who do not respond adequately to optimal standard drug therapy. Milrinone has been one of the most widely studied drugs in this regard. Even during short-term administration, its use should be closely monitored for any evidence of an increase in ventricular arrhythmias or decrease in ventricular function.