心力衰竭患者的血管反应性（VASOR）：一项前瞻性观察性研究方案
Vasoresponsiveness in patients with heart failure (VASOR): protocol for a prospective observational study.
作者信息
van Vessem Marieke E, Beeres Saskia L M A, de Wilde Rob B P, de Vries René, Berendsen Remco R, de Jonge Evert, Danser A H Jan, Klautz Robert J M, Schalij Martin J, Palmen Meindert
机构信息
Department of Cardiology, Leiden University Medical Center, PO Box 9600, Leiden, 2300 RC, The Netherlands.
Department of Cardiothoracic Surgery, Leiden University Medical Center, PO Box 9600, Leiden, 2300 RC, The Netherlands.
出版信息
J Cardiothorac Surg. 2019 Nov 21;14(1):200. doi: 10.1186/s13019-019-1014-8.
BACKGROUND
Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved.
METHODS
This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12).
DISCUSSION
Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome.
TRIAL REGISTRATION
The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.
背景
血管麻痹是心脏手术后可能发生的一种严重并发症，尤其是在心力衰竭患者中。它是血管舒张途径激活、血管收缩途径失活以及对血管加压药产生抵抗的结果。然而，确切病因仍不清楚。心力衰竭患者血管反应性（VASOR）研究的目的是客观化并描述心力衰竭患者在心脏手术前、手术期间和手术后血管反应性的改变，并确定其中涉及的病因因素。
方法
这是一项在莱顿大学医学中心进行的前瞻性观察性研究。纳入接受体外循环心脏手术的心力衰竭患者和非心力衰竭患者。该研究分为两个纳入阶段。在第1阶段，纳入18例心力衰竭患者和18例非心力衰竭患者。在不同时间点在体内评估对血管收缩剂（去氧肾上腺素）和血管舒张剂（硝酸甘油）的血管反应性。在t1（诱导前）、t2（诱导前、开始使用强心药和/或血管加压药后）、t3（诱导后）、t4（体外循环停止后15分钟）和t5（术后1天）评估对去氧肾上腺素的反应。在t1和t5评估对硝酸甘油的反应。此外，术中收集一份含有阻力动脉的心包前脂肪组织样本。使用分离的阻力动脉构建对各种血管活性物质的浓度反应曲线，评估离体血管反应性。接下来，使用免疫组织化学和mRNA分析评估信号蛋白和受体的表达。此外，比较两组可影响心血管系统的有机化合物水平（如 copeptin、（去甲）肾上腺素、心房钠尿肽、脑钠肽、N末端脑钠肽前体、血管紧张素II、皮质醇、醛固酮、肾素和香草扁桃酸水平）。在第2阶段纳入期间，仅对心力衰竭患者（N = 12）和非心力衰竭患者（N = 12）进行离体血管反应性测试。
讨论
详细了解心力衰竭患者和非心力衰竭患者血管反应性的差异，可能会产生血管麻痹的治疗选择或预防策略，从而实现更安全的手术干预并改善预后。
试验注册
荷兰试验注册库（NTR），NTR5647。2016年1月26日注册。
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