Wesley Mark C, McGowan Francis X, Castro Robert A, Dissanayake Sheahan, Zurakowski David, Dinardo James A
Department of Anesthesia, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Anesth Analg. 2009 May;108(5):1425-9. doi: 10.1213/ane.0b013e3181981fbe.
Milrinone is a phosphodiesterase III inhibitor that increases intracellular cyclic adenosine monophosphate resulting in improved ventricular function and vasodilation. Increased intracellular levels of cyclic adenosine monophosphate also inhibit adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation. We hypothesized that inhibition of ADP and AA-induced platelet activation by therapeutic blood concentrations of milrinone could be quantified using TEG Platelet Mapping.
Blood was taken from 15 healthy adults who had not been taking antiplatelet medications. Milrinone was added to whole blood in three clinically relevant concentrations (30, 100, and 300 ng/mL). Conventional thromboelastography (TEG) and TEG Platelet Mapping were performed on whole blood without milrinone and at each of these three concentrations.
Increased blood concentrations of milrinone were associated with increased inhibition of ADP and AA-induced platelet activation (P < 0.0001). Milrinone at a blood concentration of 300 ng/mL markedly impaired the platelet activation response to ADP and AA.
Therapeutic blood concentrations of milrinone exhibit a significant inhibitory effect on ADP and AA-induced platelet activation as determined by TEG Platelet Mapping, without affecting the conventional kaolin-activated TEG. We suggest that TEG Platelet Mapping results be interpreted with caution in patients being treated with milrinone, and other drugs that modify platelet cyclic nucleotide concentrations.
米力农是一种磷酸二酯酶III抑制剂,可增加细胞内环磷酸腺苷水平,从而改善心室功能并引起血管舒张。细胞内环磷酸腺苷水平升高还可抑制二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集。我们假设,使用血栓弹力图血小板功能分析(TEG Platelet Mapping)可以定量米力农治疗血药浓度对ADP和AA诱导的血小板活化的抑制作用。
采集15名未服用抗血小板药物的健康成年人的血液。将米力农以三种临床相关浓度(30、100和300 ng/mL)添加到全血中。对未添加米力农的全血以及这三种浓度下的全血进行传统血栓弹力图(TEG)和TEG血小板功能分析。
米力农血药浓度升高与对ADP和AA诱导的血小板活化的抑制作用增强相关(P < 0.0001)。血药浓度为300 ng/mL的米力农显著损害了血小板对ADP和AA的活化反应。
如TEG血小板功能分析所示,米力农治疗血药浓度对ADP和AA诱导的血小板活化具有显著抑制作用,且不影响传统高岭土激活的TEG。我们建议,在接受米力农及其他可改变血小板环核苷酸浓度的药物治疗的患者中,应谨慎解读TEG血小板功能分析结果。