Children's Heart Center, Newark Beth Israel Medical Center, 201 Lyons Avenue, Newark, NJ 07112, USA.
J Heart Lung Transplant. 2012 Jun;31(6):642-7. doi: 10.1016/j.healun.2012.02.020. Epub 2012 Mar 21.
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies have explored how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies have demonstrated systemic endothelial dysfunction in adults with pulmonary hypertension; however, adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH.
In this single-center, prospective, cross-sectional study we examined brachial artery flow-mediated dilation (FMD), a nitric oxide-mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity.
Thirteen patients and 13 controls were studied, ranging in age from 6 to 20 years. FMD was decreased in IPAH subjects compared with controls (5.1 ± 2.1% vs 9.7 ± 2.0%; p < 0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R(2) = 0.34, p = 0.035), and inversely with tricuspid regurgitation velocity (R(2) = 0.57, p = 0.019) and right ventricular myocardial performance index (R(2) = 0.44, p = 0.028).
The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.
特发性肺动脉高压（IPAH）是一种危及生命的疾病，表现为进行性肺血管重塑、肺血流受损和右心衰竭。大多数研究都探讨了肺内皮功能如何调节疾病的发病机制。我们假设 IPAH 是一种进行性的全血管病变，影响肺和全身血管床，全身内皮功能障碍与疾病严重程度相关。最近的研究表明，成人肺动脉高压存在全身内皮功能障碍；然而，成人往往还有其他影响内皮功能的合并症。尚未在患有 IPAH 的儿童中探索全身内皮功能。
在这项单中心、前瞻性、横断面研究中，我们检查了特发性肺动脉高压儿童和匹配对照者的肱动脉血流介导的扩张（FMD），这是一种一氧化氮介导的、内皮依赖性的反应。FMD 测量结果与 IPAH 严重程度的临床和超声心动图测量结果进行了比较。
共研究了 13 例 IPAH 患儿和 13 例对照者，年龄 6 至 20 岁。与对照组相比，IPAH 患儿的 FMD 降低（5.1 ± 2.1%比 9.7 ± 2.0%；p < 0.0001）。在 IPAH 患儿中，FMD 与心指数直接相关（R² = 0.34，p = 0.035），与三尖瓣反流速度（R² = 0.57，p = 0.019）和右心室心肌收缩指数（R² = 0.44，p = 0.028）呈负相关。
患有 IPAH 的儿童存在全身内皮功能障碍，且其与 IPAH 严重程度密切相关，表明 IPAH 是一种全身性血管病变。尽管 IPAH 的发病率通常与肺血管疾病相关，但全身血管变化也可能与疾病的发病机制和进展有关。进一步研究全身和肺内皮功能障碍的共同机制可能有助于未来治疗 IPAH。
