Amrinone-a phosphodiesterase III inhibitor-is used in the treatment of acut
e heart failure. In addition to its hemodynamic effects, amrinone has been
shown to inhibit thromboxane synthesis in vitro. We investigated the effect
s of amrinone on thromboxane, prostaglandin, and leukotriene synthesis in h
umans. Eight healthy male volunteers took part in this single-blind study i
n which either amrinone (a 1.5 mg/kg bolus in 30 min and after that 10 mu g
/kg/min for 1 h 30 min) or placebo (0.9% NaCl) were infused. Amrinone infus
ion increased systolic blood pressure but had no significant effect on dias
tolic blood pressure or heart rate. Amrinone did not modulate thromboxane B
-2 synthesis stimulated by either spontaneous clotting or calcium-ionophore
A23187 in whole blood. Amrinone had no effects on prostaglandin E-2 or leu
kotriene E-4 production in A23187-stimulated whole blood, nor did it affect
urinary excretion of 11-dehydrothromboxane B-2 or 2,3-dinor-6-keto-prostag
landin F-1 alpha, the index metabolites of thromboxane A(2) and prostacycli
n productions, respectively. We conclude that amrinone has no effects on ei
cosanoid production in humans at: the dose level used in this study, and th
at the hemodynamic effects noticed are not mediated via cyclooxygenase or l
ipoxygenase products of arachidonic acid metabolism.