Abstract:
During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study investigates the effects of platelet transfusion on the major pro-aggregatory, pro-inflammatory and immunomodulatory markers of platelets. Platelets from 20 patients, 10 who received platelet transfusion and 10 without, were subjected to flow cytometery where P-selectin and CD40 ligand (CD40L) expressions and PAC-1 binding (activation-specific anti GPIIb/GPIIIa antibody) analysed at five-time points of 24 h before surgery, immediately, 2 h, 24 h and 1 week after surgery. Analysis of intra-platelet transforming growth factor-beta-1 (TGF-β1) was also conducted using western blotting. Patients with platelet transfusion showed increased levels of P-selectin, CD40L and intra-platelet TGF-β1 2-h after surgery compared to those without transfusion (p < 0.05). PAC-1 binding was increased 24 h after surgery in transfused patients (p < 0.05). Given the significant post-transfusion elevation of platelet TGF-β1, P-sel/CD40L reduction in transfused patients a week after was of much interest. This study showed for the first time the significant effects of platelet transfusion on the pro-inflammatory, pro-aggeregatory and immunomodulatory state of platelets in CABG patients, which manifested with immediate, midterm and delayed consequences. While the increased pro-inflammatory conditions manifested as an immediate effect of platelet transfusion, the pro-aggregatory circumstances emerged 24 h post-transfusion. A week after surgery, attenuations of pro-inflammatory markers of platelets in transfused patients were shown, which might be due to the immunomodulatory effects of TGF-β1.
摘要:
在冠状动脉旁路移植术(CABG)期间,外科手术,特别是心脏主要动脉的操作,诱导显著的炎症状态,可能损害血小板功能,达到需要输注血小板的程度。鉴于储存的血小板是生物介质的主要来源,这项研究调查了血小板输注对主要促聚集的影响,血小板的促炎和免疫调节标志物。20名患者的血小板,10人接受血小板输注,10人没有,在手术前24小时的五个时间点进行流式细胞术,其中P-选择素和CD40配体(CD40L)表达和PAC-1结合(激活特异性抗GPIIb/GPIIIa抗体)分析,立即,2h,术后24h和1周。还使用蛋白质印迹法进行血小板内转化生长因子-β-1(TGF-β1)的分析。血小板输注患者P-选择素水平升高,手术后2小时的CD40L和血小板内TGF-β1与未输血者相比(p<0.05)。输血患者术后24小时PAC-1结合增加(p<0.05)。鉴于输血后血小板TGF-β1的显着升高,一周后输血患者的P-sel/CD40L降低非常有趣。这项研究首次显示了血小板输注对促炎,CABG患者血小板的促聚集和免疫调节状态,表现为立即,中期和延迟后果。虽然促炎性疾病的增加表现为血小板输注的直接作用,促聚集情况出现在输血后24小时.手术后一周,显示输注患者的血小板促炎标志物减弱,这可能是由于TGF-β1的免疫调节作用。