T hirteen percent of global mortality has been associated with arterial hypertension. Approximately 34% of the total adult population worldwide is hypertensive, and 13% of this segment of the population is further categorized as having resistant hypertension (RHTN).1 Criteria for the diagnosis of RHTN are the following: any patient requiring ≥3 antihypertensive drugs, including a diuretic, and still maintaining a blood pressure (BP) >140/90 mm Hg.2 RHTN has been previously described as a multifactorial phenomenon involving multiple biological mechanisms; however, the hyperactivity of the sympathetic nervous system plays a paramount role in the onset, maintenance, and progression of RHTN. 3 The renal sympathetic nervous system, composed of afferent and efferent nerves, courses immediately adjacent to the wall of the renal artery. 4 The afferent renal sensory nerves, with neuronal cell bodies located in the ipsilateral dorsal root ganglia, modulate the central sympathetic outflow by providing sensory information from mechanoreceptors and chemoreceptors in the renal tissue. Renal injuries (ie, hypoxia) increase afferent sensory signals, resulting in an increase in efferent sympathetic nerve activity, peripheral arterial vasoconstriction, and subsequent increase in arterial BP. The efferent renal sympathetic nerves transmit signals from the central sympathetic nervous system to the kidneys (ie, renal vasculature, tubules, and juxtaglomerular apparatus). Efferent renal sympathetic activity is moderated by an inhibitory renorenal reflex and central sympathetic nervous system outflow. Elevated efferent renal sympathetic activity increases sodium reabsorption and renin release and causes renal arterial vasoconstriction, leading to hypertension. Catheter-based ablation of afferent and efferent sympathetic nerves surrounding the renal arteries has been proposed Background-Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN. Methods and Results-Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thick...
In this small, preclinical study, we introduce a new non-vascular system to treat resistant hypertension. If the current clinical experience confirms efficacy and safety, this approach may be one way to treat patients who cannot be treated with the standard percutaneous arterial devices.
<b><i>Introduction:</i></b> The blood pressure (BP) response to arterial renal denervation (RDN) is variable. <b><i>Methods:</i></b> This study examined the effectiveness of renal pelvic denervation (RPD) on BP, heart rate (HR), norepinephrine (NE), and histopathology in 42 swine. NE levels were measured immediately, 7, 14, 30, and 90 days after RPD. Intra-arterial BP and HR were measured throughout RPD and after 14 days in 5 swine. <b><i>Results:</i></b> During the procedure, RPD immediately reduced systolic BP (−20.6 ± 18.3 mm Hg), diastolic BP (−6.0 ± 8.3 mm Hg), and HR (−5.4 ± 5.6 bpm), which remained decreased at follow-up. The porcine kidneys had a mean NE reduction of 76% directly post procedure and 60% after 7 days, 64% after 14 days, 57% after 30 days, and 65% after 90 days. Histopathological examination confirmed nerve ablation. <b><i>Conclusions:</i></b> These preliminary findings suggest that the renal pelvis nerve ablation is an encouraging target for RDN. Clinical trials are required to test the feasibility of RPD in human hypertension.
Introduction:Several renal denervation (RDN) systems are currently under investigation for treatment of hypertension by ablation of renal sympathetic nerves. The procedural efficacy of devices, however, is variable and incompletely understood. This study aimed at investigating procedural and anatomical predictors of RDN efficacy by comparing two radiofrequency catheter systems in a porcine model.Methods:Domestic swine were assigned into two treatment groups (n = 10) and one sham group (n = 3). Bilateral RDN in main and in branch segments of renal arteries was performed using two different multielectrode catheter systems [Symplicity Spyral (SPY) and IberisBloom (IBB)]. After 7 days, measurement of norepinephrine (NEPI) tissue concentrations and histological analyses have been performed.Results:Renal NEPI tissue concentration following RDN was significantly reduced when compared with Sham (SPY: −95 ± 3% vs. Sham, P < 0.001; IBB: −88 ± 11% vs. Sham, P < 0.001). Histological evaluation showed comparable lesion depth and lesion area (lesion depth: SPY-main 6.26 ± 1.62 mm vs. SPY-branch 3.49 ± 1.11 mm; IBB-main 5.93 ± 1.88 mm vs. IBB-branch: 3.26 ± 1.26 mm, P < 0.001; lesion area: SPY-main 43.5 ± 29.5 mm2 vs. SYP-branch 45.0 ± 38.0 mm2; IBB-main 52.3 ± 34.8 mm2 vs. IBB-branch 44.0 ± 42.6 mm2, P = 0.77; intergroup SPY vs. IBB, P = 0.73). Histological investigations documented a significant correlation between number of ablations per millimeter length of renal artery and reduction in NEPI tissue concentration.Conclusion:The two devices under investigation demonstrated similar histopathological lesion characteristics and similar reduction of renal NEPI levels. An increase in number of ablations per millmeter length of renal artery resulted in improved efficacy and reduced variability in treatment effects.
Objectives We aimed to investigate the safety of radiofrequency (RF)‐renal denervation (RDN) on branch renal arteries (RAs) in a porcine model. Background The efficacy of RF‐RDN was enhanced by treatment of the branch RA, in addition to the main RA. However, there are concerns regarding the safety of RF‐RDN on branch RA because of their smaller diameter and proximity to the kidney. Methods RF was delivered to 24 RA from 12 swine. A total of 8 RA from 4 swine were untreated. Treated RA were examined by angiography and histopathology at 7, 30, and 90 days. Serum creatinine concentration, biophysical parameters during RF delivery, and renal norepinephrine concentration were also assessed. Results Angiography revealed minimal late lumen loss and diameter stenosis in the main and branch RA at any time point. There was no change in serum creatinine after RF‐RDN. Histopathologically, no augmentation of medial damage or neointimal formation was found in branch RA compared with main RA. No or minimal damage to surrounding tissues including the kidneys, ureters, lymph nodes, and muscles was observed at any time point in both the main and branch RA. Equivalent electrode temperature in the main and branch RA was achieved by automatic adjustment of output power by the generator. The renal norepinephrine concentration was significantly lower in the treated group compared with the untreated group. Conclusions RF‐RDN on branch RA was safe in a porcine model, with stenosis‐free healing of treated arteries and negligible kidney damage at 7, 30, and 90 days.
Objective and Design: The search for improved stenting technologies to treat peripheral artery disease is trending toward biodegradable self-expanding shape-memory stents that, as of now, still suffer from the acute trade-off between deliverability and luminal stability: Higher deliverability leads to lower lumen stability, vessel recoil, and stent breakage. This study was aimed at the development and testing of a self-expanding bioresorbable poly(l,l-lactide-co-ε-caprolactone) stent that was designed to produce confident self-expansion after efficient crimping, as well as quick bioresorption, and sufficient radial force. Materials and Methods: Bench tests were employed to measure shape-memory properties, radial force, and hydrolytic degradation of the stent. The porcine model was employed to study deliverability, lumen stability, biocompatibility, and stent integrity. A total of 32 stents were implanted in the iliac arteries of 16 pigs with 15 to 180 day follow-up periods. The stented vessels were studied by angiography and histological evaluation. Results: Recovery of the diameter of the stent due to shape-memory effect was equal to 90.6% after 6Fr crimping and storage in refrigeration for 1 week. Radial force measured after storage was equal to 0.7 N/mm. Technical success of implantation in pigs (after the delivery implemented by pusher) was 94%. At 180 days, no implanted stents were found to be fragmented: All of the devices remained at the site of implantation with no stent migration and all stents retained their luminal support. Only moderate inflammation and neoepithelialization were detected by histological assessment at 60, 90, 120, and 180 days. Lumen loss at 180 days was less than 25% of the vessel diameter. Conclusions: The stent with the mechanical and chemical properties described in this study may present the optimal solution of the trade-off between deliverability and luminal stability that is necessary for designing the next generation stent for endovascular therapy of peripheral arterial disease.
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