Shah Binita, Allen Nicole, Harchandani Bhisham, Pillinger Michael, Katz Stuart, Sedlis Steven P, Echagarruga Christina, Samuels Svetlana Krasnokutsky, Morina Pajazit, Singh Prabhjot, Karotkin Liza, Berger Jeffrey S
Department of Medicine, Division of Cardiology, New York University School of Medicine, 227 E 30th Street, Office 835, New York, NY, 10016, USA.
Department of Medicine, Section of Cardiology, Veterans Affairs New York Harbor Health Care System, New York, NY, USA.
Inflammation. 2016 Feb;39(1):182-189. doi: 10.1007/s10753-015-0237-7.
The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.
秋水仙碱在稳定型缺血性心脏病患者中的心脏保护机制尚不确定。我们在体外测试了不同浓度的秋水仙碱对血小板活性的影响,并在10名健康受试者中给予了临床上相关的1.8毫克口服负荷剂量,给药时间为1小时。数据以中位数[四分位间距]表示。体外添加秋水仙碱仅在超治疗浓度下降低了透光率血小板聚集,但在治疗浓度下降低了单核细胞-血小板聚集(MPA)和中性粒细胞-血小板聚集(NPA)。对健康受试者给予1.8毫克秋水仙碱对透光率血小板聚集没有显著影响,但降低了MPA的程度(从28%[22 - 57]降至22%[19 - 31],p = 0.05)和NPA的程度(从19%[16 - 59]降至15%[11 - 30],p = 0.01),给药后2小时血小板表面PAC - 1的表达(平均荧光强度(MFI)从370[328 - 555]降至333 MFI[232 - 407],p = 0.02)和P - 选择素的表达(从351 MFI[269 - 492]降至279[226 - 364],p = 0.03),以及血小板与胶原蛋白的黏附(从10.2%[2.5 - 32.6]降至2.0%[0.2 - 9.5],p = 0.09)。因此,在临床相关浓度下,秋水仙碱可降低血小板活性表面标志物的表达并抑制白细胞 - 血小板聚集,但不抑制同型血小板聚集。