Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3772_Библиотеки_им_академика_М_И_Перельмана

are >3mm depth, and with some nerves at 8mm depth or greater [3]. In a porcine model, only 48–55% of renal sym­pathetic nerves are located within the rst 2.5mm of tissue depth [4]. In human renal arteries studied, Atherton etal. reported that, within a depth of 2.5mm, most nerves identi­ed were at a distance 0.5–1.0mm from the intima-lumen interface [5]. Nevertheless, the authors recognized that tis­sue was not well preserved at a depth greater than 2.5mm and could, therefore, not be evaluated and some sympathetic nerves were identied beyond 2.5mm depth in those speci­mens that contained preserved tissue for analysis. In con­trast, Sakakura etal. examined renal arteries from 20 human autopsy subjects. Fifty percent of sympathetic nerve bers were located at greater than 2.8 mm distance from the intima-lumen interface and 25% beyond 4.7mm [3]. Since the average depth of RF ablation at the power used in the Symplicity trials (8 Watts) is in the range of 2–3mm, it may be challenging or impossible to achieve adequate renal sym­pathetic nerve disruption without jeopardizing the renal arterial wall with RF-thermal energy, particularly without utilizing cooling during ablation. In fact, endothelial denu­dation, organizing thrombus, disruption and thickening of the internal elastic lamina and necrotic myocytes can be found after RF pulmonary vein isolation in an animal model (albeit at energy levels that typically exceed those used for renal denervation and at a different location [pulmonary veins]) [6]. Similarly, cellular swelling and coagulation of connective tissue within the media and adventitia have been shown after catheter- based RF renal denervation in a por­cine model [7]. In a small study in humans, examination of the arterial wall with optical coherence tomography imme­diately after single- or multi-electrode RF denervation dem­onstrated endothelial- intimal edema and local thrombus formation in the majority of renal arteries [8]. Though lon­ger-term consequences of such changes may be uncommon, at 6-month follow-up after RF denervation in an animal model, brosis of the deep media and underlying adventitia, external elastic lamina disruption and intimal thickening at the denervation site has been observed [9]. In humans, lon­ger-term histological follow- up after renal denervation does not exist for obvious reasons. However, an autopsy report of a woman who died 12days after undergoing renal denerva­tion with the single- electrode RF energy Symplicity (Medtronic Inc., Minneapolis, MN, USA) device described nerve injury limited to a 2mm distance from the lumen-to­intima surface and wedge-shaped damage to all layers of the vasculature with a broad base at the intima [10]. As a conse­quence of vascular injury, renal artery stenoses may occur, and have been reported after RF as well as ultrasound energy application [11–14]. Whether this is the result of the energy application alone, manipulation of the renal artery, or both, remains unclear. The most recent sham-controlled trials suggest that renal artery stenosis occurs very rarely, if at all,

(anticipated with energy delivery) is absent as the delivery microneedles penetrate the renal artery by approximately 3mm, and distribution of alcohol is essentially limited to the adventitia and perivascular space [36]. Second, tissue depths of up to 1cm can be reached ensuring more complete dener­vation [36]. Third, in the absence of medial injury, periproce­dural pain is typically absent or less pronounced, requiring minimal analgesia and sedation. Fourth, there are virtually no anatomic limitations to the length of the renal artery and few limitations to the diameter. Moreover, the procedural and uoroscopy time is short and the amount of contrast needed to perform the procedure small. For example, in the European Postmarket Study using the Peregrine Catheter (details below), the procedural time (skin to skin) was 49minutes, uoroscopy time 10.8min and total contrast vol­ume 92ml [37]. In contrast, in the SYMPLICITY SPYRAL trials using the SYMPLICITY SPYRAL catheter, the total amount of contrast used was 271ml (ON-med) [24] and pro­cedural time 100 min (OFF-med) [38]. In the Radiance HTN-Solo trial using the Paradise-US RDN catheter, the average procedure time was 72min. Finally, no generator or accessory equipment is needed limiting procedural costs and complexity. In light of these advantages, there is substantial interest in the further evaluation of the safety and efcacy of catheter-based, alcohol-mediated renal sympathetic denerva­tion, as discussed below.

Given the predictable tissue injury after local application, alcohol has been successfully used to treat a number of con­ditions including, but not limited to hypertrophic obstructive cardiomyopathy [44], chronic pain [45], spasticity [39], cysts [46, 47] and some malignancies [48].

meaningful extravasation of blood has been detected despite

47.5 ng/g after neurolysis with 0.6 ml of alcohol) com­pared to control animals (median of 286ng/g). This repre­sents a 76% and 83% reduction, respectively, compared to control animals (p<0.001).

6-month angiography (interpreted by an independent core

The aim of the study was to assess renal cortical efferent sym­pathetic nerve activity before and 8weeks after renal denerva­tion. Renal cortical efferent sympathetic nerve activity was measured by positron emission computed tomography (PET ­CT) using 11-C-methylreboxetine (CMRB), a norepinephrine transporter ligand, and 6-18F-uorodopoamine (FDA), a sub­strate for the cell membrane norepinephrine transporter. Whereas CMRB decreased by 30%, FDA increased (no sig­nicant change occurred in three control patients). The reduc­tion of CMRB suggests a reduction in efferent sympathetic nerve activity. The increase in FDA could be caused by a reduction in vesicular exocytosis and accumulation of FDA in residual neurons (expected with reduced efferent sympa­thetic nerve activity) or, alternatively, by a compensatory increase in norepinephrine transporter activity in residual sympathetic neurons. There was a reduction in mean ambu­latory systolic blood pressure in three of the four patients (−9mm Hg, p=0.058). There was no change in supine mus­cle sympathetic nerve activity (MSNA). While there was no change in plasma markers of neurhormonal activation, uri- nary cathecholmamie levels were numerically lower after denervation.

Some important technical considerations may assist in cases of challenging anatomy. In anticipated difcult renal artery anatomy, consideration may be given to using an 8F guide catheter rather than 7F to allow a buddy wire (e.g.