Thiamylal and pentobarbital have opposite effects on human platelet aggregation in vitro.
The effects of barbiturates on human platelet function are not fully understood. We designed the present study to clarify the effects of thiamylal and pentobarbital on human platelet aggregation and to elucidate the underlying mechanisms in vitro. Human platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, arachidonic acid (AA), and (+)-9,11-epithia-11,12-methano-thromboxane A(2) (STA(2)), measured with an 8-channel light transmission aggregometer, was compared in the absence and presence of thiamylal or pentobarbital. To estimate thromboxane A(2) (TXA(2)) receptor binding affinity, Scatchard analysis was done using [(3)H]-S145, a specific TXA(2) receptor antagonist. STA(2)-TXA(2) receptor binding assay was also examined. The release of AA was determined in platelets preincubated with [(3)H]-AA and stimulated by ADP, using a liquid scintillation analyzer. Cytosolic free calcium concentration ([Ca(2+)](i)) was measured in fluo-3/AM-loaded platelets using a fluorometer. Thiamylal enhanced, but pentobarbital suppressed, ADP- and epinephrine-induced platelet aggregation, but they did not affect AA- or STA(2)-induced platelet aggregation. They had no effect on TXA(2) receptor binding affinity. Although thiamylal increased and pentobarbital decreased release of [(3)H]-AA from ADP-stimulated platelets, both barbiturates had no effect on ADP-induced [Ca(2+)](i) increase. We conclude that thiamylal enhances but pentobarbital suppresses human platelet aggregation in vitro. These effects of barbiturates are mediated by altered AA release without affecting [Ca(2+)](i) increase.


CONCLUSIONS
Thiamylal enhances but pentobarbital suppresses human platelet aggregation in vitro. These effects are attributed to altered arachidonic acid release from platelets, possibly by the effects of phospholipase A(2), but not secondary to altered cytosolic free calcium concentration.
Departments of *Anesthesia and †Orthopedic Surgery, Kyoto University Hospital, Kyoto; and ‡Department of Anesthesia, Shizuoka City Hospital, Shizuoka, Japan.
Masami
M
Sato
Hideo
H
Hirakata
Takefumi
T
Nakagawa
Kyoko
K
Arai
Kazuhiko
K
Fukuda
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010424:Pentobarbital / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000187:drug effects; D013840:Thiamylal / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005456:Fluorescent Dyes; D006993:Hypnotics and Sedatives; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013840:Thiamylal; D016718:Arachidonic Acid; D010424:Pentobarbital; D002118:Calcium; D016257:Fura-2; D007213:Indomethacin