Bidirectional effects of dexmedetomidine on human platelet functions in vitro

Abstract

Platelets express the imidazoline (I)-receptor, I1 and I2, as well as the α2-adrenoceptor. Although dexmedetomidine, a selective α2-adrenoceptor agonist with some affinity for the I-receptor is expected to affect platelet function, the effects of dexmedetomidine on platelet functions remain unclear. In the present study, we investigated the effects of dexmedetomidine on human platelet functions in vitro. The effects of dexmedetomidine on platelet aggregation were examined using aggregometers. The formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an enzyme immunoassay. In addition, P-selectin expression in platelets was estimated by flow cytometry. We showed that dexmedetomidine enhances platelet aggregation. But in the presence of yohimbine, an α2-antagonist, dexmedetomidine suppressed platelet aggregation. Efaroxan, an I1-antagonist, and methylene blue, a soluble guanylate cyclase inhibitor, abolished the suppressive effect of dexmedetomidine, whereas idazoxan, an I2-antagonist, showed no effect. Dexmedetomidine suppressed cAMP formation and enhanced P-selectin expression in platelets, and these effects were inhibited by yohimbine. Dexmedetomidine increased cGMP formation in platelets in the presence of yohimbine, and this increase was suppressed by efaroxan. These results demonstrated that dexmedetomidine has both enhancing and suppressive effects on human platelet functions through its action on the α2-adrenoceptor and on the I1-imidazoline receptor, respectively.

Dexmedetomidine Does Not Affect Platelet Function Measured With TEG 6S and Platelet Mapping Assay in Whole Blood

“…In contrast to the results of the present study, Kawamoto et al 4 reported in a previous study that dexmedetomidine enhances platelet aggregation measured using light transmission aggregometry with platelet rich plasma. The possible reasons for the discordance with our results might be methodological differences.…”

“…3 A recent study reported that high doses of dexmedetomidine induce adenosine diphosphate (ADP)-triggered platelet aggregation via alpha 2 -adrenoceptors in platelet-rich plasma. 4 Because high platelet reactivity to ADP and high thrombininduced clot strength measured using thromboelastography (TEG) are well-known risk factors for ischemic events in patients undergoing percutaneous coronary intervention, 5 the effect of dexmedetomidine on platelet aggregation and clot formation could be a pivotal issue. Based on the results of a previous study, 4 the authors hypothesized that dexmedetomidine could induce platelet aggregation and clot formation in whole blood and platelet-rich plasma.…”

Comparative In Vitro Study of Various α2-Adrenoreceptor Agonist Drugs for Ticagrelor Reversal

“…As expected, ADP decreased cAMP level compared with control (4 (3-15) vs. 114 (81-128) pmol/10 9 platelets) and ticagrelor-inhibited ADP-induced suppression of intracellular cAMP (131 (97-150) vs. 4 (3-15) pmol/10 9 platelets, Figure 4A). Combining ADP and either epinephrine, norepinephrine, or brimonidine in the presence of ticagrelor fully restored suppression of intracellular cAMP production, achieving the same level as obtained with ADP alone in the absence of ticagrelor (16 (9-17), 20 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), or 23 (17-24) pmol/10 9 platelets, respectively). Adding dexmedetomidine induced a moderate reduction in cAMP concentration compared with the combination of ADP and ticagrelor (61 (53-67) vs. 131 (97-150) pmol/10 9 platelets) whereas clonidine had only a faint effect (102 (88-104) vs. 131 (97-150) pmol/10 9 platelets).…”

“…Since I 1 -receptor stimulation induces guanylate cyclase activation and the subsequent increase in the intracellular cGMP level, dexmedetomidine and clonidine can also participate in platelet aggregation inhibition [17]. Consequently, dexmedetomidine and clonidine have both enhancing and suppressive effects on platelet functions through their opposite action on α 2 -adrenoceptors and on I 1 -imidazoline receptors, respectively [18]. In our experimental conditions, these two antagonist mechanisms resulted in potentiation of ADP-induced platelet aggregation insufficient to induce platelet aggregation in the presence of ticagrelor.…”

Rocuronium Has a Suppressive Effect on Platelet Function via the P2Y12 Receptor Pathway In Vitro That Is Not Reversed by Sugammadex

“…Therefore, information on the effects of perioperative drugs, including anesthetics, on platelet function is important for patient care. We have described the effects on platelets of various anesthetics used during the perioperative period [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], but the effects on human platelets of many drugs used perioperatively remain to be clarified. Rocuronium ((+)-(17β-acetoxy-3α-hydroxy-2β-morpholino-5α-androstan-16β-yl)-1-allyl-1-pyrrolidinium bromide), an aminosteroid nondepolarizing neuromuscular blocker, is widely used for anesthesia and intensive care [ 8 ], but its effect on human platelet functions has not been examined.…”