Propofol Inhibits Human Platelet Aggregation Induced by Proinflammatory Lipid Mediators

In Brief 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.