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ANESTHETIC PHARMACOLOGY

Thiamylal and Pentobarbital Have Opposite Effects on Human Platelet Aggregation In Vitro

Masami Sato, MD^*, Hideo Hirakata, MD^*, Takefumi Nakagawa, MD, Kyoko Arai, MD, and Kazuhiko Fukuda, MD^*

Departments of *Anesthesia and Orthopedic Surgery, Kyoto University Hospital, Kyoto; and Department of Anesthesia, Shizuoka City Hospital, Shizuoka, Japan

Address correspondence and reprint requests to Hideo Hirakata, MD, Department of Anesthesia, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan. Address e-mail to hirakata{at}kuhp kyoto-u.ac.jp.

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 A₂ (STA₂), measured with an 8-channel light transmission aggregometer, was compared in the absence and presence of thiamylal or pentobarbital. To estimate thromboxane A₂ (TXA₂) receptor binding affinity, Scatchard analysis was done using [³H]-S145, a specific TXA₂ receptor antagonist. STA₂-TXA₂ receptor binding assay was also examined. The release of AA was determined in platelets preincubated with [³H]-AA and stimulated by ADP, using a liquid scintillation analyzer. Cytosolic free calcium concentration ([Ca²⁺]_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 STA₂-induced platelet aggregation. They had no effect on TXA₂ receptor binding affinity. Although thiamylal increased and pentobarbital decreased release of [³H]-AA from ADP-stimulated platelets, both barbiturates had no effect on ADP-induced [Ca²⁺]_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 [Ca²⁺]_i increase.

IMPLICATIONS: 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 A₂, but not secondary to altered cytosolic free calcium concentration.