Rothman Alexander M K, Arnold Nadine D, Chang William, Watson Oliver, Swift Andrew J, Condliffe Robin, Elliot Charlie A, Kiely David G, Suvarna S Kim, Gunn Julian, Lawrie Allan
From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
Circ Cardiovasc Interv. 2015 Nov;8(11):e002569. doi: 10.1161/CIRCINTERVENTIONS.115.002569.
Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level.
Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters.
Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety.
肺动脉高压是一种具有高发病率和死亡率且治疗选择有限的毁灭性疾病。最近的研究表明,肺动脉去神经支配在实验模型和早期临床试验中可改善肺血流动力学。我们旨在评估肺动脉周围的神经分布,确定射频肺动脉去神经支配对血管收缩诱导的急性肺动脉高压的影响,并在组织学水平上证实肺动脉去神经支配。
组织学评估确定了近端肺动脉周围神经的环形分布。神经直径较小、数量较多,且在肺动脉分叉远端更靠近肺动脉壁的管腔侧。为了确定肺动脉去神经支配的效果,通过静脉输注血栓素A2类似物在8头猪中诱导急性肺动脉高压。将动物分为两组,一组使用原型射频导管和发生器进行肺动脉去神经支配,另一组进行假手术。肺动脉去神经支配导致平均肺动脉压和肺血管阻力降低,心输出量增加。肺动脉管腔表面的消融病变伴有外膜神经的组织学和生化改变,并与改善的血流动力学参数相关。
肺动脉去神经支配为肺动脉高压患者提供了一种新的治疗选择可能性。需要进一步开展工作以确定其长期疗效和安全性。