Molecular Function and Imaging Program, The National Cardiac PET Centre, Division of Cardiology, Department of Medicine and the Cardiac Research Methods Centre, University of Ottawa Heart Institute and University of Ottawa, 40 Ruskin Street, Ottawa, ON, K1Y 4W7, Canada.
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
J Nucl Cardiol. 2021 Apr;28(2):407-422. doi: 10.1007/s12350-020-02494-6. Epub 2021 Jan 26.
Little is known about the sequelae of chronic sympathetic nervous system (SNS) activation in patients with pulmonary arterial hypertension (PAH) and right heart failure (RHF). We aimed to, (1) validate the use of [11C]-meta-hydroxyephedrine (HED) for assessing right ventricular (RV) SNS integrity, and (2) determine the effects of β-receptor blockade on ventricular function and myocardial SNS activity in a PAH rat model.
PAH was induced in male Sprague-Dawley rats (N = 36) using the Sugen+chronic hypoxia model. At week 5 post-injection, PAH rats were randomized to carvedilol (15 mg·kg·day oral; N = 16) or vehicle (N = 16) for 4 weeks. Myocardial SNS function was assessed with HED positron emission tomography(PET).
With increasing PAH disease severity, immunohistochemistry confirmed selective sympathetic denervation within the RV and sparing of parasympathetic nerves. These findings were confirmed on PET with a significant negative relationship between HED volume of distribution(DV) and right ventricular systolic pressure (RVSP) in the RV (r = -0.90, p = 0.0003). Carvedilol did not reduce hemodynamic severity compared to vehicle. RV ejection fraction (EF) was lower in both PAH groups compared to control (p < 0.05), and was not further reduced by carvedilol. Carvedilol improved SNS function in the LV with significant increases in the HED DV, and decreased tracer washout in the LV (p < 0.05) but not RV.
PAH disease severity correlated with a reduction in HED DV in the RV. This was associated with selective sympathetic denervation. Late carvedilol treatment did not lead to recovery of RV function. These results support the role of HED imaging in assessing SNS innervation in a failing right ventricle.
关于肺动脉高压（PAH）和右心衰竭（RHF）患者慢性交感神经系统（SNS）激活的后遗症知之甚少。我们旨在，（1）验证[11C]-间羟麻黄碱（HED）用于评估右心室（RV）SNS 完整性的使用，以及（2）确定β受体阻滞剂在 PAH 大鼠模型中对心室功能和心肌 SNS 活性的影响。
使用苏根+慢性低氧模型在雄性斯普拉格-道利大鼠（N=36）中诱导 PAH。在注射后第 5 周，PAH 大鼠被随机分为卡维地洛（15mg·kg·天口服；N=16）或载体（N=16）4 周。使用 HED 正电子发射断层扫描（PET）评估心肌 SNS 功能。
随着 PAH 疾病严重程度的增加，免疫组织化学证实 RV 内存在选择性去交感神经支配，而副交感神经不受影响。这些发现通过 HED 分布容积（DV）与 RV 收缩压（RVSP）之间的显著负相关在 RV 上得到证实（r=-0.90，p=0.0003）。与载体相比，卡维地洛并未降低血液动力学严重程度。与对照组相比，两组 PAH 中的 RV 射血分数（EF）均较低（p<0.05），卡维地洛并未进一步降低。卡维地洛改善了 LV 的 SNS 功能，HED DV 显著增加，LV 示踪剂清除减少（p<0.05），但 RV 未减少。
PAH 疾病严重程度与 RV 中 HED DV 的减少相关。这与选择性去交感神经支配有关。晚期卡维地洛治疗并未导致 RV 功能恢复。这些结果支持 HED 成像在评估衰竭右心室中 SNS 支配的作用。
