Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
Basic Res Cardiol. 2019 Jan 11;114(2):5. doi: 10.1007/s00395-018-0714-x.
There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.
肺动脉去神经术(PADN)作为治疗慢性毛细血管后性肺动脉高压(PH)的一种潜在手段,其疗效证据有限。我们旨在对慢性 PH 的转化模型进行 PADN 的概念验证。19 头患有慢性毛细血管后 PH(继发于肺静脉结扎)的猪被随机分为手术-PADN(使用双极射频夹)或假手术组。此外,6 头健康动物接受了经皮-PADN,以比较两种方法产生的肺动脉(PA)损伤。在手术-PADN 组中,在基线和 2 个月及 3 个月的随访时进行血流动力学评估和心脏磁共振(CMR)检查。在方案完成时进行组织学评估。18 头猪(6 头接受手术-PADN,6 头接受假手术,6 头接受经皮-PADN)完成了方案。手术夹可显示完全的 PA 壁内损伤,而经皮-PADN 后仅观察到外膜纤维的局灶性损伤。在手术-PADN 组中,两组间的血流动力学特征在基线时(平均肺动脉压(mPAP)中位数分别为 32.0 和 27.5mmHg,P=0.394 和指数化肺血管阻力(iPVR)分别为 5.9 和 4.7WU·m,P=0.394)或任何随访时(mPAP 分别为 35.0 和 35.0mmHg,P=0.236 和 iPVR 分别为 8.3 和 6.7WU·m,P=0.477)均无显著差异。在第三个月,PADN 和假手术组分别为 8.3 和 6.7WU·m,P=0.477)。手术-PADN 与 CMR/组织学上 RV 解剖或功能的任何改善均无关。在慢性毛细血管后 PH 的大动物模型中,使用手术夹进行的透壁 PADN 与中性的肺血管动力学效应相关。