357 TOLAZOLINE INHIBITION OF PLATELET AGGREGATION

Abstract

Tolazoline (TZ), an imidazoline compound with vasodilatory and histaminic properties, is used in the therapy of neonatal persistent pulmonary hypertension (PPH). Inhibition of thromboxane A2 (TBX-A) synthesis by TZ has been reported. The in-vitro effects of TZ on platelet aggregation were studied. Platelet rich plasma obtained from 6 healthy adults and from cord blood samples of 6 healthy term infants was incubated with TZ and aggregated with ADP (10μM). At increasing concentrations of TZ, decreases in maximal aggregation occurred, followed by disaggregation (mean±SEM): The relationship between TZ concentration and both maximal and 10-minute aggregation was linear up to 103 μg/ml (r≥0.88). The inhibition of primary aggregation at the highest TZ concentrations is inconsistent with TBX-A inhibition alone. Preliminary data, using a radioimmunoassay, suggest an increase in platelet cyclic AMP when incubated with TZ, perhaps mediated by hist-amine receptors. In-vivo inhibition of platelet aggregation and TBX-A release by TZ may be benefical in some forms of PPH.