Renal denervation by radiofrequency in patients with hypertension: systematic review and meta-analysis.

The Guidelines Project, which is an initiative of the Brazilian Medical Association, aims to combine information from the medical field to standardize how to conduct and assist in the reasoning and decision-making of doctors. The information provided by this project must be critically evaluated by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical condition of each patient.

Features of The Dynamics of Profibrotic Markers and Regression of Left Ventricular Hypertrophy After Renal Denervation in Patients With Resistant Hypertension and Stenosing Atherosclerosis of the Coronary Arteries.

AIM: To compare the changes in serum concentrations of matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMP) to the dynamics of blood pressure (BP) and parameters of left ventricular hypertrophy (LVH) 6 months after renal denervation (RD) in patients with resistant arterial hypertension (RAH) and complicated coronary atherosclerosis. MATERIAL AND METHODS: In 22 RAH patients with complicated coronary atherosclerosis (revascularization and/or history of myocardial infarction (MI)), 24-hour BP monitoring, echocardiography, and measurement of blood MMPs and TIMP were performed at baseline and six months after RD. The comparison group consisted of 48 RAH patients without a history of coronary revascularization or MI. RESULTS: In 6 months after RD, BP was decreased comparably in both groups. In the group of complicated atherosclerosis, there were no significant changes in profibrotic markers or LVH parameters. Thus, at baseline and after 6 months, the values of the studied indicators were the following: left ventricular myocardial mass (LVMM) 233.1±48.1 and 243.0±52.0 g, LVMM index 60.6±14.5 and 62.8±10 .9 g/m2.7, proMMP-1 4.9 [2.1; 7.7] and 3.6 [2.0; 9.4]  ng/ml, MMP-2 290.4 [233.1; 352.5] and 352.2 [277.4; 402.9] ng/ml, MMP-9 220.6 [126.9; 476.7] and 263.5 [82.9; 726.2] ng/ml, TIMP-1 395.7 [124.7; 591.4] and 424.2 [118.2; 572.0] ng/ml, respectively. In the comparison group, on the contrary, there was a significant decrease in LVMM from 273.6±83.3 g to 254.1±70.4 g, LVMM index from 67.1±12.3 to 64.0±14.4 g/m2.7, proMMP-1 from 7.2 [3.6; 11.7] to 5.9 [3.5; 10.9] ng/ml, MMP-2 from 328.9 [257.1; 378.1] to 272.8 [230.2; 343.2] ng/ml, MMP-9 from 277.9 [137.0; 524.0] to 85.5 [34.2; 225.9] ng/ml, and the MMP-9/TIMP-1 ratio from 0.80 [0.31; 1.30] to 0.24 [0.07; 0.76]. The BP dynamics in this group was inversely correlated with MMP-2 at 6 months (r=-0.38), and the MMP-9/TIMP-1 ratio was correlated with LVMM and the LVMM index at baseline (r=0.39 and r=0.39) and at 6 months (r=0.37 and r=0.32). The change in TIMP-1 from 543.9 [277.5; 674.1] to 469.8 [289.7; 643.6] ng/ml was not significant (p=0.060). CONCLUSION: In RAH patients with complicated coronary atherosclerosis, the dynamics of profibrotic biomarkers and LVH parameters after RD was absent despite the pronounced antihypertensive effect, probably due to the low reversibility of cardiovascular remodeling processes or more complex regulatory mechanisms of the MMP system.

Sympathetic Pathophysiology in Hypertension Origins: The Path to Renal Denervation.

The importance of the sympathetic nervous system in essential hypertension has been recognized in 2 eras. The first was in early decades of the 20th century, through to the 1960s. Here, the sympathetic nervous system was identified as a target for the treatment of hypertension, and an extensive range of antiadrenergic therapies were developed. Then, after a period of lapsed interest, in a second era from 1985 on, the development of precise measures of human sympathetic nerve firing and transmitter release allowed demonstration of the importance of neural mechanisms in the initiation and maintenance of the arterial blood pressure elevation in hypertension. This led to the development of a device treatment of hypertension, catheter-based renal denervation, which we will discuss.

Renal denervation in the management of hypertension.

Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and effective in lowering blood pressure (BP) and cardiovascular disease risk, BP control remains poor, and the mortality rates associated with high BP have been steadily increasing. Device-based therapies have been investigated to overcome barriers to pharmacotherapy, including non-adherence and low rates of persistence to daily medications. Among these device-based therapies, catheter-based renal denervation (RDN) has been most extensively examined over the past 15 years. In this state-of-the-art article, we summarise the rationale for RDN, review the available evidence, provide recommendations for a safe procedure, and discuss the role of RDN in current guidelines and clinical practice.

Development and validation of a predictive model for poor prognosis of communication disorders in children with cerebral palsy after cervical perivascular sympathectomy.

Cervical perivascular sympathectomy (CPVS) can improve communication disorders in children with cerebral palsy (CP); however, there are no research reports on the factors affecting surgical efficacy. This study aimed to establish a nomogram for poor prognosis after CPVS. We collected data from 313 CP patients who underwent CPVS at the Neurosurgery Cerebral Palsy Center of the Second Affiliated Hospital of Xinjiang Medical University from January 2019 to January 2023. Among them, 70% (n = 216) formed the training cohort and 30% (n = 97) the validation cohort. The general data and laboratory examination data of both groups were analyzed. In training cohort, 82 (37.96%) showed improved postoperative communication function. Logistic analysis identified motor function, serum alkaline phosphatase, serum albumin, and prothrombin activity as the prognostic factors. Using these four factors, a prediction model was constructed with an area under the curve (AUC) of 0.807 (95% confidence interval [CI], 0.743-0.870), indicating its ability to predict adverse outcomes after CPVS. The validation cohort results showed an AUC of 0.76 (95% CI, 0.650-0.869). The consistency curve and Hosmer-Lemeshow test (χ2 = 10.988 and p = 0.202, respectively) demonstrated good consistency between the model-predicted incidence and the actual incidence of poor prognosis. Motor function, serum alkaline phosphatase, serum albumin, and prothrombin activity are independent risk factors associated with the prognosis of communication disorders after CPVS. The combined prediction model has a good clinical prediction effect and has promising potential to be used for early prediction of prognosis of CPVS.

Long-Term Safety and Efficacy of Transcatheter Microwave and Radiofrequency Denervation in a Chronic Ovine Model.

BACKGROUND: Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long-term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation. METHODS AND RESULTS: Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80-120 W for 240 s-480 s) and 12 to 16 radiofrequency ablations (180 s-240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.5 months (chronic N=15), and compared with undenervated controls (N=4). Microwave RDN produced substantial circumferential perivascular injury compared with radiofrequency at both 2 weeks [area 239.8 (interquartile range [IQR] 152.0-343.4) mm2 versus 50.1 (IQR, 32.0-74.6) mm2, P <0.001; depth 16.4 (IQR, 13.9-18.9) mm versus 7.5 (IQR, 6.0-8.9) mm P <0.001] and 5.5 months [area 20.0 (IQR, 3.4-31.8) mm2 versus 5.0 (IQR, 1.4-7.3) mm2, P=0.025; depth 5.9 (IQR, 1.9-8.8) mm versus 3.1 (IQR, 1.2-4.1) mm, P=0.005] using mixed models. Renal denervation resulted in significant long-term reductions in viability of renal sympathetic nerves [58.9% reduction with microwave (P=0.01) and 45% reduction with radiofrequency (P=0.017)] and median cortical norepinephrine levels [71% reduction with microwave (P <0.001) and 72.9% reduction with radiofrequency (P <0.001)] at 5.5 months compared with undenervated controls. CONCLUSIONS: Transcatheter microwave RDN produces deep circumferential perivascular ablations without significant arterial injury to provide effective and durable RDN at 5.5 months compared with radiofrequency RDN.

Impact of Renal Denervation on Urinary Peptide-Based Biomarkers in Hypertension.

BACKGROUND: Catheter-based renal denervation (RDN) reduces blood pressure in hypertension. Urinary peptides are associated with cardiovascular and renal disease and provide prognostic information. We aimed to investigate the effect of RDN on urinary peptide-based classifiers associated with chronic kidney and heart disease and to identify urinary peptides affected by RDN. METHODS: This single-arm, single-center study included patients undergoing catheter-based RDN. Urine samples were collected before and 24 months after RDN and were analyzed using capillary electrophoresis coupled with mass spectrometry. Predefined urinary peptide-based classifiers for chronic kidney disease (CKD273), coronary artery disease (CAD238), and heart failure (HF1) were applied. RESULTS: This study included 48 patients (33% female) with uncontrolled hypertension. At 24 months after RDN, systolic blood pressure (165±17 versus 148±20 mm Hg; P<0.0001), diastolic blood pressure (90±17 versus 81±13 mm Hg; P<0.0001), and mean arterial pressure (115±15 versus 103±13 mm Hg; P<0.0001) decreased significantly. A total of 103 urinary peptides from 37 different proteins, mostly collagens, altered following RDN. CAD238, a 238 coronary artery-specific polypeptide-based classifier, significantly improved following RDN (Cohen's d, -0.632; P=0.0001). The classification scores of HF1 (P=0.8295) and CKD273 (P=0.6293) did not change significantly. CONCLUSIONS: RDN beneficially affected urinary peptides associated with coronary artery disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01888315.

Efficacy of cervical perivascular sympathectomy in improving upper limb motor function in children with cerebral palsy and construction of a predictive model.

BACKGROUND: The effectiveness of cervical perivascular sympathectomy (CPVS) in enhancing upper limb motor function in children with cerebral palsy is unclear, and the factors that influence the effectiveness of the surgery have not been documented. OBJECTIVE: To investigate the effectiveness of CPVS in enhancing upper limb motor function in children with cerebral palsy and develop a predictive chart for potential associated adverse outcomes METHODS: The study included 187 children with cerebral palsy who underwent CPVS at the Cerebral Palsy Center, Second Affiliated Hospital of Xinjiang Medical University, between January 2018 and January 2022. Patients were categorized into two groups based on prognostic outcomes: those with adverse and favorable prognoses. Demographic and laboratory data were collected and analyzed from both groups. To identify independent predictors of poor post-CPVS upper limb motor function outcomes, statistical techniques, including univariate analysis and binary logistic regression, were applied. Subsequently, these predictors were integrated to formulate a comprehensive predictive model. RESULTS: In this cohort of 187 children with cerebral palsy undergoing CPVS, 68 (36.36%) exhibited a favorable prognosis for upper limb motor function and 119 (63.64%) demonstrated an adverse prognosis. Age, motor function, and serum albumin levels were identified as significant prognostic factors via logistic regression analysis. To develop the model, we divided the sample into a training set (70%, n = 131) and a validation set (30%, n = 56). Employing motor function, serum albumin levels, and age as variables, we crafted a predictive model. The model's performance, reflected by the area under the curve was 0.813 (0.732, 0.894) in the training set and 0.770 (0.647, 0.892) in the validation set, demonstrating its robust predictive capability for post-CPVS adverse outcomes. Furthermore, the consistency curve and Hosmer-Lemeshow test (χ2 = 8.808, p = 0.359) illustrated a strong concordance between the model's predictions of poor prognosis and the actual incidence rate. CONCLUSION: CPVS has been shown to be effective in improving upper limb motor function in patients with cerebral palsy. Independent prognostic factors identified encompass motor function, age, and serum albumin levels. The composite predictive model shows potential for clinical applications.

Efficacy and safety of radiofrequency ablation versus surgical sympathectomy in palmar hyperhidrosis.

Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21-0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38-0.92; p = 0.020), postoperative pain (95% CI 0.13-0.33; p < 0.001), and surgery-related complications (95% CI 0.19-0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84-3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS.Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx .

Impact of renal denervation on patients with coronary microvascular dysfunction: study rationale and design.

AIMS: Long-standing hypertension may cause an impairment in microvascular coronary circulation, which is involved in many different cardiac conditions. Renal sympathetic denervation (RDN) has been successfully proven as a valuable therapeutic choice for patients with resistant hypertension; moreover, the procedure looks promising in other settings, such as heart failure and atrial fibrillation, given its ability to downregulate the sympathetic nervous system, which is a recognized driver in these conditions as well as in microvascular dysfunction progression. The aim of this study is to explore the effect of RDN on coronary physiology in patients with ascertained coronary microvascular dysfunction and resistant hypertension. METHODS: This is a multicenter, prospective, nonrandomized, open-label, interventional study. Consecutive patients with resistant hypertension, nonobstructive coronary artery disease (NOCAD) and documented microvascular dysfunction will be enrolled. Patients will undergo RDN by Spyral Symplicity 3 (Medtronic Inc, Minneapolis, Minnesota, USA) and reassessment of coronary microvascular function 6 months after the procedure. Primary endpoint will be the difference in the index of microcirculatory resistance. CONCLUSION: The IMPRESSION study seeks to evaluate if there is any pleiotropic effect of the RDN procedure that results in modulation of microvascular function; if observed, this would be the first evidence showing RDN as a valuable therapy to revert hypertension-related microvascular dysfunction.

Efficacy and safety of 3D reconstruction and basket multi-electrode renal denervation (RDN) for refractory hypertensive patients with chronic kidney disease.

Renal Artery Sympathetic Denervation (RDN) can lower blood pressure. Different ablation catheters (single electrode, multi-electrode) have different scopes of ablation (renal artery main stem and branches). Few studies have compared the advantages and disadvantages of different ablation catheters and different procedures in terms of antihypertensive efficacy. To compare the efficacy and safety of 3D reconstruction radiofrequency ablation (3DRA) and basket multi-electrode radiofrequency ablation (BMRA) in Renal Artery Sympathetic Denervation. Fifty-three patients with Refractory hypertension (RHT) were divided into BMRA, (n = 28) and 3DRA(n = 25). BMRA group used a stereobasket multi-electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120 s per site. 3DRA group used a NavStar pressure-monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40 s per site, and an ablation energy of 12 W. Baseline and RDN parameters and complications were compared in both groups. Home and 24 h ambulatory blood pressure, type of anti-hypertensive medication taken, and serum creatinine were followed up at 1, 3, 6, 12, and 24 months after the RDN. There were no differences in baseline characteristics between the two groups. (23.14 ± 2.00)months of follow-up in the BMRA group resulted in a total of (25.86 ± 8.61) loci ablation. (19.28 ± 7.40)months of follow-up in the 3DRA group resulted in a total of (21.04 ± 6.47)loci ablation. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline(H-SBP/mmHg: BMRA 149.9 ± 10.59 vs. baseline 168.36 ± 12.76; 3DRA 152.6 ± 14.91 vs. 164.89 ± 12.96, both p < .05). The proportion of people with 24 h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. At each follow-up time point, there were no differences in home and 24-h flow SBP, DBP, or Scr between the two groups. There were two cases of severe renal artery complications from implanted vascular stents and one case of femoral artery pseudoaneurysm in the 3DRA group. At follow-up, 1 (1.9%) patient in the 3DRA group died of unexplained death and 1 (1.9%) patient developed heart failure, and 1 (1.9%) patient in the BMRA group died of unexplained death. Basket multi-electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in reducing systolic blood pressure.

Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis.

BACKGROUND: Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies. METHODS: A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically. RESULTS: In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of -12.7±4.5 mm Hg from baseline was observed (P=0.05). Likewise, a -14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5-9.4 years; P=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up. CONCLUSIONS: Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.

Echocardiographic findings following renal sympathetic denervation for treatment resistant hypertension, the ReShape CV-risk study.

OBJECTIVE: The aim of this study was to describe and compare echocardiographic findings before renal sympathetic denervation (RDN) and 6 and 24 months after the procedure. MATERIALS AND METHODS: Patients with treatment resistant hypertension (TRH) were included in this non-randomised intervention study. RDN was performed by a single experienced operator using the Symplicity Catheter System. Echocardiographic measurements were performed at baseline, and after 6 and 24 months. RESULTS: The cohort consisted of 21 patients with TRH, with a mean systolic office blood pressure (BP) of 163 mmHg and mean diastolic BP 109 mmHg. Mixed model analysis showed no significant change in left ventricular (LV) mass index (LVMI) or left atrium volume index (LAVI) after the RDN procedure. Higher LVMI at baseline was significantly associated with greater reduction in LVMI (p < 0.001). Relative wall thickness (RWT) increased over time (0.48 mm after two years) regardless of change in BP. There was a small but significant reduction in LV end-diastolic (LVIDd) and end-systolic (LVIDs) diameters after RDN, with a mean reduction of 2.6 and 2.4 mm, respectively, after two years. Progression to concentric hypertrophy was observed only in in patients who did not achieve normal BP values, despite BP reduction after RDN. CONCLUSION: There was no reduction of LV mass after RDN. We found a small statistically significant reduction in LVIDd and LVIDs, which together with increase in RWT can indicate progression towards concentric hypertrophy. BP reduction after RDN on its own does not reverse concentric remodelling if target BP is not achieved.

NADPH oxidase 2 mediates cardiac sympathetic denervation and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced cardiomyopathy.

Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy-both of which contribute to cardiac atrophy and failure after doxorubicin treatment.

[Translated article] Topical Anticholinergics in the Management of Focal Hyperhidrosis in Adults and Children. A Narrative Review.

Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

BACKGROUND: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations. METHODS: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

Renal sympathetic denervation improves pressure-natriuresis relationship in cardiorenal syndrome: insight from studies with Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.

The aim was to evaluate the effects of renal denervation (RDN) on autoregulation of renal hemodynamics and the pressure-natriuresis relationship in Ren-2 transgenic rats (TGR) with aorto-caval fistula (ACF)-induced heart failure (HF). RDN was performed one week after creation of ACF or sham-operation. Animals were prepared for evaluation of autoregulatory capacity of renal blood flow (RBF) and glomerular filtration rate (GFR), and of the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. Their basal values of blood pressure and renal function were significantly lower than with innervated sham-operated TGR (p < 0.05 in all cases): mean arterial pressure (MAP) (115 ± 2 vs. 160 ± 3 mmHg), RBF (6.91 ± 0.33 vs. 10.87 ± 0.38 ml.min-1.g-1), urine flow (UF) (11.3 ± 1.79 vs. 43.17 ± 3.24 µl.min-1.g-1) and absolute sodium excretion (UNaV) (1.08 ± 0.27 vs, 6.38 ± 0.76 µmol.min-1.g-1). After denervation ACF TGR showed improved autoregulation of RBF: at lowest RAP level (80 mmHg) the value was higher than in innervated ACF TGR (6.92 ± 0.26 vs. 4.54 ± 0.22 ml.min-1.g-1, p < 0.05). Also, the pressure-natriuresis relationship was markedly improved after RDN: at the RAP of 80 mmHg UF equaled 4.31 ± 0.99 vs. 0.26 ± 0.09 µl.min-1.g-1 recorded in innervated ACF TGR, UNaV was 0.31 ± 0.05 vs. 0.04 ± 0.01 µmol min-1.g-1 (p < 0.05 in all cases). In conclusion, in our model of hypertensive rat with ACF-induced HF, RDN improved autoregulatory capacity of RBF and the pressure-natriuresis relationship when measured at the stage of HF decompensation.

The effects of renal denervation on blood pressure, cardiac hypertrophy, and sympathetic activity during the established phase of hypertension in spontaneously hypertensive rats.

This study aimed to investigate whether renal denervation (RDN) reduces blood pressure and attenuates cardiac hypertrophy with decreasing sympathetic activity in spontaneously hypertensive rats (SHRs), a model of essential hypertension, during the established phase of hypertension. We performed RDN or sham operation in 15-weeks-old SHRs. Thirty days after RDN, mean blood pressure measured by telemetry, heart weight, left ventricular wall thickness assessed by echocardiography, and urinary norepinephrine levels were significantly decreased in the RDN group compared to the Sham group. Furthermore, oxidative stress, as indicated by thiobarbituric acid reactive substances, in the rostral ventrolateral medulla, a pivotal region regulating basal sympathetic tone, was significantly decreased in the RDN group. In conclusion, RDN reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in SHRs. These findings highlight the sympathoinhibitory effect of RDN and suggest that RDN may be a potential therapy for hypertensive cardiac hypertrophy. Renal denervation reduces blood pressure and attenuates cardiac hypertrophy with sympathoinhibition in the established phase of hypertension in spontaneously hypertensive rats. This study highlights the sympathoinhibitory effect of renal denervation and suggests that renal denervation may be a potential therapy for hypertensive cardiac hypertrophy.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1ß, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. CONCLUSIONS: Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.