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Antiplatelet effect of the anaesthetic drug propofol: influence of red blood cells and leucocytes
Author(s) -
De La Cruz J P,
Páez M V,
Carmona J A,
Sánchez De La Cuesta F
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702927
Subject(s) - platelet , prostacyclin , whole blood , chemistry , adenosine , propofol , pharmacology , adenosine diphosphate , cyclic guanosine monophosphate , nitric oxide , arachidonic acid , platelet rich plasma , thromboxane a2 , cyclic adenosine monophosphate , biochemistry , medicine , platelet aggregation , enzyme , receptor , organic chemistry
The present study was designed to investigate the mechanism of the antiplatelet action of the anaesthetic propofol in vitro . Human whole blood was incubated with different concentrations of propofol and its solvent Intralipid®. 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). Propofol‐induced inhibition of platelet aggregation was greater in whole blood (IC 50 80–136 μ M ) than in PRP (IC 50 >600 μ M ), except when aggregation was induced by arachidonic acid, in which case the antiaggregatory effect of the anaesthetic was similar in both media (IC 50 72–85 μ 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. 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. 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. 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.British Journal of Pharmacology (1999) 128 , 1538–1544; doi: 10.1038/sj.bjp.0702927