TICLOPIDINE INCREASES NITRIC-OXIDE GENERATION IN HEART-TRANSPLANT RECIPIENTS - A POSSIBLE NOVEL PROPERTY OF TICLOPIDINE

The objective of this study was to evaluate the effects of ticlopidine on the generation of eicosanoids and nitric oxide in heart-transplant recipients. In a randomized double-blind study, we studied the urinar y excretion of the stable metabolites of thromboxane, prostacyclin, an d nitric oxide before and after ticlopidine (250 mg/day). Platelet agg regation was significantly reduced in ticlopidine-treated patients [fr om 40.2 +/- 24.2% of maximal aggregation to 14.7 +/- 8.2% in response to adenosine diphosphate (ADP); p < 0.001] but not in the placebo grou p, confirming the efficacy of the drug with that dosage in these speci fic patients. The 24-h urinary excretion of prostacyclin metabolites w as not modified by ticlopidine (1,865 +/- 833 ng/24 h at day 14 and 1, 664 +/- 425 ng/24 h at day 0), whereas the excretion of thromboxane B- 2 tended to increase in the ticlopidine group (from 3,854 +/- 1,163 ng /24 h at day 0 to 5,014 +/- 2,914 ng/24 h at day 14), although not sig nificantly. The excretion of nitric oxide metabolites (although not di fferent from that of healthy nonimmunosuppressed subjects) was signifi cantly (p < 0.005) increased in the ticlopidine group (from 3.082 +/- 1,683 mu mol/24 h at day 0 to 4,133 +/- 2,262 mu mol/24 h at day 14), but not in controls. Thus ticlopidine does not reduce prostacyclin but increases the systemic generation of nitric oxide, both substances ha ving major antiplatelet and vasodilator properties. Further studies ar e warranted to examine whether ticlopidine could reduce the incidence of thromboembolic complications in these patients and whether this pos sible novel property of ticlopidine is restricted to immunosuppressed heart-transplant recipients.