Tzafriri Abraham R, Keating John H, Markham Peter M, Spognardi Anna-Maria, Stanley James R L, Wong Gee, Zani Brett G, Highsmith Debby, O'Fallon Patrick, Fuimaono Kristine, Mahfoud Felix, Edelman Elazer R
Departments of Applied Sciences and Pathology, CBSET, Lexington, MA 02421, USA.
Biosense Webster Inc., a Johnson & Johnson Company, Irwindale, CA 91765, USA.
Sci Transl Med. 2015 Apr 29;7(285):285ra65. doi: 10.1126/scitranslmed.aaa3236.
Renal denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area, and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water-rich tissues (media, lymph nodes, etc.), not at the electrode-tissue interface. Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering periarterial ablation. Seven days after multielectrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes.
肾去神经支配术（RDN）是常规治疗无效的高血压患者的一种治疗选择。临床试验已证明其疗效存在差异。为了解该治疗临床成功反应的决定因素，我们整合了血管内射频RDN的猪模型和计算模型。可控单电极去神经支配术导致消融区的几何形状在弧度、面积和深度上有所不同，这取决于相邻组织亚结构的组成。计算模拟预测，施加的功率密度受组织亚结构影响，并在软脂肪外膜与富含水的组织（中膜、淋巴结等）之间的电导率不连续处达到峰值，而非在电极 - 组织界面处。电极冲洗通过清除从组织内部扩散的热量来保护电极附近的动脉壁组织，而不改变动脉周围消融。多电极治疗7天后，肾脏去甲肾上腺素和血压降低。血压降低与变性神经的大小加权数量相关，这意味着该治疗降低高血压的有效性取决于神经损伤和消融的程度，而这又由电极部位的组织微观解剖结构决定。这些结果可能解释了患者对RDN反应的差异，并为实现更可靠的治疗效果指明了方向。
