Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)
研究概览
简要总结
Ischemia reperfusion injury may be attenuated by HO-1 induction. Our previous data confirmed strong HO-1 induction in peripheral blood cells following heme arginate infusion in healthy humans. Furthermore, we could demonstrate the amelioration of experimental ischemia reperfusion injury in the calf musculature by heme arginate in healthy subjects as measured by functional MRI.
Therefore, we propose that HO-1 induction in the human heart may be a suitable target to mitigate cardiac ischemia-reperfusion injury.
The HO-1 induction will be assessed in a clinical trial by myocardial biopsy prior to and after aortic cross-clamping in subjects with or without preceding heme arginate treatment in two different dosages. The HO-1 expression will also be measured in the clinical trials in peripheral blood mononuclear cells. As additional outcome, levels of myoglobin, creatine-kinase and troponin T and reactive oxygen species will be measured in plasma according to standard laboratory procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Heme arginate (high dose)
24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 3 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.
干预措施: Heme arginate 3mg/kg (Drug)
Heme arginate (low dose)
24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 1 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.
干预措施: Heme arginate 1mg/kg (Drug)
Placebo
24 hours prior to the planned surgical aortic valve replacement, subjects received a single intravenous infusion of an equivalent volume of 0.9% sodium chloride solution.
干预措施: Placebo (Drug)
结局指标
主要结局
Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)
时间窗: intraoperative
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)
时间窗: intraoperative
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)
时间窗: intraoperative
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)
时间窗: intraoperative
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Myocardial HO-1 Protein Concentrations (Atrial Tissue)
时间窗: intraoperative
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass.The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)
时间窗: intraoperative
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
次要结局
未报告次要终点
研究者
Martin Andreas, M.D.
M.D., PhD
Medical University of Vienna