The Effect Of Radiofrequency Ablation At Renal Arterial Intima And Adventitia On Renal Sympathetic Nerve Activity In Dogs: A Comparative Study

BackgroundRenal sympathetic nervous system plays an important role in the developmentand progression of hypertension，so people raise a hot wave of the renal denervationto treat resistant hypertension. Renal denervation by kidney partial denervationdisrupts renal sympathetic nerve activity, which affects the release of catecholaminesubstances, resulting in blood pressure lowering. In recent years, catheter-based renalsympathetic denervation has been performed in substantial and sustained bloodpressure lowering in patients with severe and medically resistant hypertension.However, it has potential failure to denervate deeper nerve fibres that may run from2-10mm deep from the intimal surface adequately due to the heat sink as the thermalinjury traverses the renal artery wall from within the renal artery, resultingin“non-responders” and/or an inadequate BP lowering response, low proportion whoachieved target systolic blood pressure values of less than140mm Hg and theunchanged average number of antihypertensive medications. It is necessary to explorea more effective method of renal denervation to treat resistant hypertension. ObjectiveThe study observed the efficacy and safety of renal denervation from the intimaand adventitia of renal arteries, and compared the effect of renal denervation fromrenal intima and adventitia on renal sympathetic nerve activity.Methods14beagles were randomly divided into control group (n=4) and treatment group(n=10). One renal artery in every beagle of treatment group was randomly assigned tointimal group, and another renal artery in the same beagle of treatment group withintimal group was assigned to adventitial group. Control group only underwent renalangiogram, the arteries in intimal group underwent renal denervation from the insideof the renal artery after renal angiogram, and the arteries in adventitia groupunderwent renal denervation from outside the renal artery after renal angiogram bysurgical procedure. At1month and3months follow-up renal artery angiogram wereperformed, and the sympathetic nervous activity substances were analysed.Results1. Renal norepinephrine (NE) content in control group, intimal group and adventitialgroup were554.556±108.091ng/g,388.438±114.397ng/g,281.685±32.723ng/g,respectively, after follow-up1month. Compared with control group, renal NEcontent in intimal group and adventitial group significantly decreased (P=0.015,P<0.001, respectively), and NE content in adventitial group was lower than that inintimal group (P=0.001). Renal norepinephrine (NE) content in control group,intimal group and adventitial group were570.806±24.617ng/g,404.616±14.226ng/g,325.561±12.989ng/g, respectively, after follow-up3month.Compared with control group, renal NE content in intimal group and adventitialgroup significantly decreased (both P<0.001), and NE content in adventitial groupwas lower than that in intimal group (P=0.003). 2. Renal artery HE staining showed an normal nerve fascicles surrounded by thinfibrous connective tissue sheaths in the control group, in contrast, a nerve fasciclefrom all denervation vessels with marked densification of collagen fibers in thesurrounding connective tissue and a perineurium that appears thickened, and theperineurium was thicker in the arteries of adventitial group than in the arteries ofadventitial group.3. Western blot showed that Tyrosine hydroxylase (TH) protein expression in intimalgroup and adventitial group was significant lowered compared with control group(both P<0.01). TH protein expression in intimal group was significant higher thanadventitial group (P<0.01). At3months after renal denervation, TH content inintimal group and adventitial group also significantly decreased compared withcontrol group (both P<0.01), and TH content in adventitial group was lower thanthat in intimal group (P<0.01).4. There was a renal artery stenosis and a renal atrophy in intimal group afterfollow-up1month, no serious adverse events occurred within3months in otheranimals.Conclusions1. Renal denervation from the inside of renal artery and renal denervation from theoutside of renal artery both could suppress renal sympathetic nerve activity.2. Renal sympathetic nerve activity suppression of renal denervation from the outsideof renal artery was more effective than the inside of renal artery.3. Renal denervation from the outside of renal artery was safer. Renal denervationfrom the inside of renal artery has the risk of renal artery stenosis.