Phosphodiesterase inhibitors: alterations in systemic and coronary hemodynamics

This paper reviews the effect on myocardial contractility, left ventricular afterload and left ventricular distensibility induced by the following phosphodiesterase inhibitors: Enoximone, piroximone, RO 13-6438, amrinone and milrinone. For all these compounds, direct positive inotropic effects have been shown in experimental studies. For amrinone and milrinone, a direct stimulating effect on myocardial contractility has been demonstrated by an increase in dP/dtmax when intracoronary applications of the compounds were performed. A direct stimulating effect on the myocardium was also demonstrated for enoximone and piroximone by analyzing the systolic pressure versus end-systolic volume ratio. For all of the phosphodiesterase inhibitors, a marked decrease of systemic vascular resistance has been observed indicating direct peripheral vasodilation. Although it has been demonstrated that phosphodiesterase inhibition increases left ventricular distensibility, the nature of this effect is not clear. For most of the phosphodiesterase inhibitors an increase in myocardial oxygen requirements was demonstrated due to overall contractility increase. However, these phosphodiesterase inhibitors induce increased coronary blood flow in excess so that a direct effect of these compounds on the coronary vasculature has been postulated. The clinical significance of such changes, however, remains unclear.