Intravenous Heme Arginate Induces HO-1 (Heme Oxygenase-1) in the Human Heart: Randomized, Placebo-Controlled, Safety, and Feasibility Pharmacokinetic StudyBrief Report
Intravenous Heme Arginate Induces HO-1 (Heme Oxygenase-1) in the Human Heart: Randomized, Placebo-Controlled, Safety, and Feasibility Pharmacokinetic StudyBrief Report
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DOI：
10.1161/atvbaha.118.311832
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发表时间：
2018-11-01
影响因子：
8.7
通讯作者：
Wolzt, Michael
中科院分区：
文献类型：
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作者：
Andreas, Martin;Oeser, Claudia;Wolzt, Michael
目的诱导血红素氧合酶-1（HO-1）的表达可预防或减轻缺血再灌注损伤。我们先前评估了其在外周血单个核细胞中单次全身施用精氨酸血红素后的体内诱导。目前的试验旨在评估HO-1的药理学组织诱导在人类心脏与血红素精氨酸invivo.Approach和结果患者计划为传统的主动脉瓣置换术接受安慰剂（n=8），1 mg/kg（n=7）或3 mg/kg（n=9）血红素精氨酸静脉输注术前24小时。在主动脉阻断前和阻断释放后立即进行右心室活检。此外，部分切除右心耳进行分析。HO-1蛋白和mRNA的浓度测定组织样本和外周血单个核细胞手术前和手术后72小时。未发生研究药物相关不良事件。观察到对心肌HO-1 mRNA水平的强烈剂量依赖性效应（右心室：7.95.0 vs 88.649.1 vs 203.6 +/- 148.7; P=0.002;右心房：10.8 +/- 8.8 vs 229.8 +/- 173.1 vs 392.7 +/- 195.7; P=0.001）。心房组织中HO-1蛋白浓度的显著增加（8401 ± 3889 vs 28585 ± 10692 vs 29022 ± 8583; P
Objective HO-1 (heme oxygenase-1) induction may prevent or reduce ischemia-reperfusion injury. We previously evaluated its in vivo induction after a single systemic administration of heme arginate in peripheral blood mononuclear cells. The current trial was designed to assess the pharmacological tissue induction of HO-1 in the human heart with heme arginate in vivo.Approach and Results Patients planned for conventional aortic valve replacement received placebo (n=8), 1 mg/kg (n=7) or 3 mg/kg (n=9) heme arginate infused intravenously 24 hours before surgery. A biopsy of the right ventricle was performed directly before aortic cross-clamping and after cross-clamp release. In addition, the right atrial appendage was partially removed for analysis. HO-1 protein and mRNA concentrations were measured in tissue samples and in peripheral blood mononuclear cells before to and up to 72 hours after surgery. No study medication-related adverse events occurred. A strong, dose-dependent effect on myocardial HO-1 mRNA levels was observed (right ventricle: 7.95.0 versus 88.649.1 versus 203.6 +/- 148.7; P=0.002 and right atrium: 10.8 +/- 8.8 versus 229.8 +/- 173.1 versus 392.7 +/- 195.7; P=0.001). This was paralleled by a profound increase of HO-1 protein concentration in atrial tissue (8401 +/- 3889 versus 28585 +/- 10692 versus 29022 +/- 8583; P