Antiplatelet effect of the anaesthetic drug propofol:: influence of red blood cells and leucocytes

1 The present study was designed to investigate the mechanism of the antiplatelet action of the anaesthetic propofol in vitro. 2 Human whole blood was incubated with different concentrations of propofol and its solvent Intralipid(R) We determined, platelet aggregometry in whole blood, platelet-enriched plasma (PRP). PRP plus red blood cells (RBC), and PRP plus leucocytes (LC); platelet production of thromboxane B-2 (TxB(2)), ATP release by platelet dense granules, adenosine uptake by RBC, intraplatelet levels of cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), and LC production of nitric oxide (NO). 3 Propofol-induced inhibition of platelet aggregation was greater in whole blood (IC50 80-136 mu M) than in PRP (IC50 > 600 mu M), except when aggregation was induced by arachidonic acid, in which case the antiaggregatory effect of the anaesthetic was similar in both media (IC50 72-85 mu M). Inhibition of platelet aggregation correlated significantly with inhibition of TxB(2) synthesis (r(2) = 0.83). Propofol also inhibited granular ATP release; this effect was greatest in whole blood. 4 The presence of RBC or LC increased the antiaggregatory effect of propofol, mainly when agent. Intralipid inhibited the uptake of adenosine by RBC, collagen was used as aggregating however this effect probably does not contribute significantly to its antiaggregatory effect. 5 The anaesthetic potentiated the NO-cyclic GIMP pathway, mainly by increasing the synthesis of NO by LC. Intralipid had no effect on the NO-cyclic GMP pathway in the LC-platelet interaction. 6 Propofol inhibited platelet aggregation in human whole blood, possibly through the sum of the effects of Intralipid on the platelet-RBC interaction and the increased synthesis of NO by LC in the platelet-LC interaction.