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 B2 (TxB2), 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 microM) than in PRP (IC50>600 microM), 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 microM). Inhibition of platelet aggregation correlated significantly with inhibition of TxB2 synthesis (r2=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 collagen was used as aggregating agent. Intralipid inhibited the uptake of adenosine by RBC, however this effect probably does not contribute significantly to its antiaggregatory effect. 5. The anaesthetic potentiated the NO-cyclic GMP 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.
De La Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain.
Páez
M V
MV
Carmona
J A
JA
De La Cuesta
F S
FS
D000241:Adenosine / Q000097:blood / Q000493:pharmacokinetics; D000255:Adenosine Triphosphate / Q000097:blood / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D018686:Anesthetics, Intravenous; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000241:Adenosine; D015742:Propofol