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ANESTHETIC PHARMACOLOGY

Propofol Inhibits Human Platelet Aggregation Induced by Proinflammatory Lipid Mediators

Olivier Fourcade, MD PhD^*, Marie-Françoise Simon, PhD, Lawrence Litt, MD PhD, Kamran Samii, MD^*, and Hugues Chap, MD PhD

Department of Anesthesia, Purpan Hospital, University of Toulouse, Toulouse, France; Institut National de la Santé et de la Recherche Médicale, Unit 326, Purpan Hospital, Toulouse, France; and Department of Anesthesia, University of California, San Francisco, California

Address correspondence and reprint requests to Olivier Fourcade, MD, PhD, Service d’Anesthésie-Réanimation, Hôpital Purpan, Place du Docteur Baylac, 31059 Toulouse Cedex, France. Address e-mail to fourcade.o{at}chu-toulouse.fr

Lysophosphatidic acid (LPA), platelet-activating factor (PAF), and thromboxane A₂ are proinflammatory lipid mediators that activate surface receptors on platelets, producing increased intracellular calcium, which is necessary for aggregation. We investigated propofol’s effect on platelet aggregation and intracellular calcium mobilization caused by these three agonists. Platelets from human volunteers were incubated in buffers containing LPA (1 µM), U46619 (thromboxane A₂ analog; 1 µM), or PAF (10 nM). Propofol emulsion or 2,6-diisopropylphenol (propofol without fat emulsion) dissolved in ethanol was added to achieve concentrations of propofol used clinically: 5 or 10 µg/mL. After 2 min, aggregation or intracellular calcium concentrations were measured with optical techniques. Propofol emulsion and propofol in ethanol produced similar inhibition of platelet aggregation induced by LPA, PAF, and U46619 in a dose-dependent fashion. LPA, PAF, and U46619 each caused significant increases in intracellular calcium that were not modified by propofol. Because propofol does not significantly alter intracellular calcium increases caused by receptor activation, inhibition appears to act distal to platelet receptors, inositol phosphate 3, and phospholipase C. Because the three lipid mediators play a key role in inflammation, their inhibition by propofol might be clinically important.

IMPLICATIONS: Propofol inhibited the platelet aggregation induced by three proinflammatory lipid mediators (lysophosphatidic acid, platelet-activating factor, and thromboxane A₂). The absence of inhibition of intracellular calcium increase induced by these agonists suggests that propofol acts distal to platelet receptors.