Alam S R, Lewis S C, Zamvar V, Pessotto R, Dweck M R, Krishan A, Goodman K, Oatey K, Harkess R, Milne L, Thomas S, Mills N M, Moore C, Semple S, Wiedow O, Stirrat C, Mirsadraee S, Newby D E, Henriksen P A
British Heart Foundation/Centre for Population Health Sciences, University of Edinburgh Centre for Cardiovascular Science, Edinburgh, UK.
Edinburgh Clinical Trials Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Heart. 2015 Oct;101(20):1639-45. doi: 10.1136/heartjnl-2015-307745. Epub 2015 Aug 26.
Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery.
In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320).
There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury.
(EudraCT 2010-019527-58, ISRCTN82061264).
弹性蛋白酶抑制因子是一种有效的内源性中性粒细胞弹性蛋白酶抑制剂，在缺血再灌注损伤的临床前模型中可预防心肌炎症和损伤。我们研究了弹性蛋白酶抑制因子是否能抑制冠状动脉搭桥术（CABG）手术期间诱导的心肌缺血再灌注损伤。
在一项随机双盲安慰剂对照平行组临床试验中，87例行CABG手术的患者按1:1随机分为两组，分别在麻醉诱导后、胸骨切开术前静脉注射200mg弹性蛋白酶抑制因子或生理盐水安慰剂。心肌损伤通过48小时内心脏肌钙蛋白I的释放量（曲线下面积（AUC））来衡量，心肌梗死通过MRI确定。缺血后炎症通过血浆标志物来测量，包括AUC高敏C反应蛋白（hs-CRP）和髓过氧化物酶（MPO）。输注弹性蛋白酶抑制因子是安全的，在最初24小时内血浆弹性蛋白酶抑制因子浓度增加了3000倍以上，弹性蛋白酶活性抑制率超过50%。这并没有在48小时内减轻心肌损伤（AUC肌钙蛋白I的几何均数比（弹性蛋白酶抑制因子/安慰剂）为0.74（95%CI 0.47至1.15，p=0.18）），尽管对高敏检测的事后分析显示，弹性蛋白酶抑制因子治疗组患者在6小时时肌钙蛋白I浓度较低（中位数2.4 vs 4.1μg/L，p=0.035）。弹性蛋白酶抑制因子对心肌梗死无影响（弹性蛋白酶抑制因子组7/34例，安慰剂组5/35例），对炎症标志物也无影响：AUC hs-CRP的平均差异为499mg/L/48小时（95%CI -207至1205，p=0.16），AUC MPO的平均差异为238ng/mL/48小时（95%CI -235至711，p=0.320）。
没有充分证据表明单剂量弹性蛋白酶抑制因子治疗抑制中性粒细胞弹性蛋白酶可减轻CABG诱导的缺血再灌注损伤后的心肌损伤和炎症。
（欧洲临床试验数据库编号2010-019527-58，国际标准随机对照试验编号82061264）
Zotero 插件
