用血浆源性α-1抗胰蛋白酶抑制心肌缺血再灌注后的炎症损伤：VCU-α1RT研究的事后分析
Inhibiting the Inflammatory Injury After Myocardial Ischemia Reperfusion With Plasma-Derived Alpha-1 Antitrypsin: A Post Hoc Analysis of the VCU-α1RT Study.
作者信息
Abouzaki Nayef Antar, Christopher Sanah, Trankle Cory, Van Tassell Benjamin Wallace, Carbone Salvatore, Mauro Adolfo Gabriele, Buckley Leo, Toldo Stefano, Abbate Antonio
机构信息
VCU Pauley Heart Center Richmond, VA.
Department of Pharmacotherapy and Outcome Sciences, School of Pharmacy Richmond, VA.
出版信息
J Cardiovasc Pharmacol. 2018 Jun;71(6):375-379. doi: 10.1097/FJC.0000000000000583.
BACKGROUND
Despite the benefits of reperfusion in limiting myocardial injury, the infarct size continues to expand after reperfusion because of secondary inflammatory injury. Plasma-derived alpha-1 antitrypsin (AAT) inhibits the inflammatory injury in myocardial ischemia and reperfusion. To explore the effects of plasma-derived AAT on the inflammatory response to ischemia-reperfusion injury, we analyzed time-to-reperfusion and enzymatic infarct size estimates in a post hoc analysis of the VCU-α1RT clinical trial (clinicaltrials.gov NCT01936896).
METHODS
Ten patients with ST-segment elevation acute myocardial infarction (STEMI) were enrolled in an open-label, single-arm treatment study of Prolastin C, plasma-derived AAT, at 60 mg/kg infused intravenously within 12 hours of reperfusion. Biomarkers were measured serially over the first 72 hours, and patients were followed clinically for the occurrence of new-onset heart failure, recurrent MI, or death. Twenty patients with STEMI who had been enrolled in previous randomized trials with identical inclusion/exclusion criteria and had been assigned to placebo served as historical controls.
RESULTS
Time to percutaneous coronary intervention and time to drug did not significantly differ between groups. AAT-treated patients had a significantly shorter time-to-peak creatine kinase myocardial band (CK-MB) values (525 [480-735] vs. 789 [664-959] minute, P = 0.005) and CK-MB area under the curve (from 1204 [758-2728] vs. 2418 [1551-4289] U·day, P = 0.035), despite no differences in peak CK-MB (123 [30-196] vs. 123 [71-213] U/mL, P = 0.71).
CONCLUSIONS
A single administration of Prolastin C given hours after reperfusion in patients with STEMI led to a significant shorter time to peak and area under the curve for CK-MB, despite similar peak CK-MB values. These preliminary data support the hypothesis that Prolastin C shortens the duration of the ischemia-reperfusion injury in patients with STEMI.
背景
尽管再灌注对限制心肌损伤有益，但由于继发性炎症损伤，再灌注后梗死面积仍会继续扩大。血浆源性α-1抗胰蛋白酶（AAT）可抑制心肌缺血再灌注中的炎症损伤。为了探究血浆源性AAT对缺血再灌注损伤炎症反应的影响，我们在VCU-α1RT临床试验（clinicaltrials.gov NCT01936896）的事后分析中分析了再灌注时间和酶学梗死面积估计值。
方法
10例ST段抬高型急性心肌梗死（STEMI）患者参加了一项开放标签、单臂治疗研究，使用血浆源性AAT普洛莱斯坦C，在再灌注后12小时内静脉输注60mg/kg。在最初的72小时内连续测量生物标志物，并对患者进行临床随访，观察新发心力衰竭、复发性心肌梗死或死亡的发生情况。20例符合相同纳入/排除标准且曾被分配至安慰剂组的STEMI患者作为历史对照。
结果
两组之间经皮冠状动脉介入治疗时间和给药时间无显著差异。AAT治疗组患者肌酸激酶同工酶（CK-MB）峰值出现时间显著缩短（525[480-735]分钟对789[664-959]分钟，P = 0.005），CK-MB曲线下面积也显著减小（1204[758-2728]对2418[1551-4289]U·天，P = 0.035），尽管CK-MB峰值无差异（123[30-196]对123[71-213]U/mL，P = 0.71）。
结论
STEMI患者再灌注数小时后单次给予普洛莱斯坦C，尽管CK-MB峰值相似，但CK-MB峰值出现时间和曲线下面积显著缩短。这些初步数据支持普洛莱斯坦C可缩短STEMI患者缺血再灌注损伤持续时间这一假说。
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