Lei Ye, Haider Husnain Kh, Chusnsheng Wang, Zhiqiang Cheng, Hao Chen, Kejian Hu, Qiang Zhao
Department of Surgery, National University Hospital, National University of Singapore, 117597 Singapore.
Cardiovasc Drugs Ther. 2003 Jul;17(4):343-8. doi: 10.1023/a:1027399707418.
To investigate the dose dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension (PH) after cardiopulmonary bypass (CPB).
Thirty-two patients with pulmonary arterial pressure (PAP) above 60 mmHg were recruited. They were assigned randomly to control (Group A, n = 8), and treated groups (Group B with aprotinin = 0.5 x 10(5) KIU/Kg, and Group C with aprotinin = 1.0 x 10(5) KIU/Kg, n = 12 each group). Blood samples were collected at various intervals of time and analyzed, from "0" hour (before CPB as baseline), at the completion of CPB, 4 hours and 24 hours after CPB, to measure the concentrations of interleukin 1beta (IL-1beta), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha).
All the biomarkers significantly increased after CPB. There was no significant difference in cytokine levels between Group A and group B after CPB. But IL-1beta, IL-8 and TNF-alpha of Group C were not only significantly lower than Group A (p < 0.05), but also lower than Group B at various time points after CPB (p < 0.05). IL-10 of group C was significantly higher than Group A and Group B after CPB (p < 0.05).
High dose aprotinin can suppress the release of pro-inflammatory cytokines IL-1beta, IL-8 and TNF-alpha, and enhance the release of IL-10 in patients with PH after CPB. For patients having PH, there exists a simple and potential way to reduce the inflammatory response by applying high dose aprotinin.
探讨抑肽酶对体外循环(CPB)后肺动脉高压(PH)患者促炎细胞因子加重的剂量依赖性作用。
招募32例肺动脉压(PAP)高于60 mmHg的患者。他们被随机分为对照组(A组,n = 8)和治疗组(B组使用抑肽酶= 0.5×10(5) KIU/Kg,C组使用抑肽酶= 1.0×10(5) KIU/Kg,每组n = 12)。在不同时间间隔采集血样并进行分析,从“0”小时(CPB前作为基线)、CPB结束时、CPB后4小时和24小时,以测量白细胞介素1β(IL-1β)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)的浓度。
CPB后所有生物标志物均显著升高。CPB后A组和B组细胞因子水平无显著差异。但C组的IL-1β、IL-8和TNF-α不仅在CPB后各时间点显著低于A组(p < 0.05),也低于B组(p < 0.05)。CPB后C组的IL-10显著高于A组和B组(p < 0.05)。
高剂量抑肽酶可抑制CPB后PH患者促炎细胞因子IL-1β、IL-8和TNF-α的释放,并增强IL-10的释放。对于患有PH的患者,应用高剂量抑肽酶存在一种简单且潜在的减轻炎症反应的方法。