CBSET, Inc., Lexington, Massachusetts; Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
CBSET, Inc., Lexington, Massachusetts.
Transl Res. 2019 Nov;213:100-111. doi: 10.1016/j.trsl.2019.07.012. Epub 2019 Jul 30.
This study sought to evaluate perisplenic artery nerve distribution and the feasibility of splenic artery denervation (SDN). The NEXION radiofrequency catheter was used to perform SDN in healthy and inflammatory arthritis pigs. Splenic artery anatomy, nerve distribution, and splenic norepinephrine (NEPI) levels were evaluated before and after SDN. Perisplenic artery nerves were primarily distributed within 2.5 mm of the arterial lumen and were largely sympathetic on the basis of tyrosine hydroxylase expression. The pancreas, tended to be circumferentially positioned around the proximal splenic artery, typically >2.5 mm from the lumen, ensuring that most of the nerves could be targeted without affecting this sensitive organ. The mid segment of the splenic artery was relatively free of contact with the adjacent pancreas. Splenic NEPI levels and nerve abundance followed a decreasing gradient from the proximal to distal splenic artery. SDN resulted in significant reductions in splenic NEPI levels at day 14 (60.7%, P = 0.024) in naïve pigs and day 45 (100%, P = 0.001) in inflammatory arthritis pigs. There was no significant effect of SDN on joint soft tissue injury or circulating inflammatory markers in the inflammatory arthritis model. The majority of perisplenic arterial nerves are within close proximity of the lumen and are primarily sympathetic efferent fibers. Nerves in the mid-segment may be the preferred SDN target given their proximity to the artery and paucity of periarterial off-target organs. SDN appears safe and effective at reducing splenic NEPI levels.
本研究旨在评估脾动脉周围神经分布和脾动脉去神经支配(SDN)的可行性。使用 NEXION 射频导管对健康和炎症性关节炎猪进行 SDN。在 SDN 前后评估脾动脉解剖结构、神经分布和脾去甲肾上腺素(NEPI)水平。脾动脉周围神经主要分布在动脉管腔 2.5mm 以内,根据酪氨酸羟化酶表达,大部分为交感神经。胰腺通常位于脾动脉近端周围,通常距离管腔>2.5mm,呈环形排列,这确保了大部分神经可以被靶向,而不会影响这个敏感的器官。脾动脉中节段与相邻胰腺接触相对较少。脾 NEPI 水平和神经丰度从脾动脉近端到远端呈递减梯度。在未受刺激的猪中,SDN 在第 14 天(60.7%,P=0.024)和在炎症性关节炎猪中第 45 天(100%,P=0.001)导致脾 NEPI 水平显著降低。在炎症性关节炎模型中,SDN 对关节软组织损伤或循环炎症标志物没有显著影响。大多数脾动脉周围神经与管腔接近,主要是交感传出纤维。中节段的神经可能是 SDN 的首选靶标,因为它们靠近动脉且周围没有靶器官。SDN 似乎安全有效,可降低脾 NEPI 水平。