Objective: To compare the venodilator potencies of the phosphodiesterase (PDE) III inhibitors amrinone and enoximone with the unspecific PDE inhibitors theophylline and pentoxifylline in human hand veins in vivo.
Methods: Eighteen healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein technique. After preconstriction with the selective alpha1-adrenergic-receptor agonist phenylephrine dose-response curves were constructed for amrinone (1-270 microg x min(-1)), enoximone (1-270 microg x min(-1)), theophylline (5-1500 microg x min(-1)) and pentoxifylline (2-877 microg x min(-1)) in a random order on separate occasions. Due to limitation in the maximum dose infused in order to avoid systemic effects, full dose-response curves could not be constructed for pentoxifylline. In this case, the individual dose of pentoxifylline and theophylline producing 50% venodilation were compared.
Results: All PDE inhibitors induced dose-dependent venodilation. The value of maximum venodilation was the same for amrinone, enoximone and theophylline. The infusion rate needed to induce 50% of maximum venodilation (ED50) was not significantly different for amrinone (geometric mean, 8.8 microg x min(-1)) and enoximone (14.2 microg x min(-1)), whereas the ED50 of theophylline (84.0 microg x min(-1)) was significantly higher than either amrinone or enoximone. The dose necessary to dilate the vein to 50% the maximum dilation (as determined during sodium chloride infusion) was significantly higher for pentoxifylline than for theophylline (409 vs 71 microg x min(-1)).
Conclusions: These findings demonstrate that enoximone and amrinone have similar venodilatory potency which is six times higher than that of theophylline. The least potent vasodilator in this study was pentoxifylline.