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JACC. Cardiovascular Interventions Dec 2020
Topics: Humans; Kidney; Sympathectomy; Treatment Outcome
PubMed: 33357532
DOI: 10.1016/j.jcin.2020.10.019 -
Journal of Cachexia, Sarcopenia and... Dec 2021Ageing and cachexia cause a loss of muscle mass over time, indicating that protein breakdown exceeds protein synthesis. Deuterium oxide (D O) is used for studies of...
BACKGROUND
Ageing and cachexia cause a loss of muscle mass over time, indicating that protein breakdown exceeds protein synthesis. Deuterium oxide (D O) is used for studies of protein turnover because of the advantages of long-term labelling, but these methods introduce considerations that have been largely overlooked when studying conditions of protein gain or loss. The purpose of this study was to demonstrate the importance of accounting for a change in protein mass, a non-steady state, during D O labelling studies while also exploring the contribution of protein synthesis and breakdown to denervation-induced muscle atrophy.
METHODS
Adult (6 months) male C57BL/6 mice (n = 14) were labelled with D O for a total of 7 days following unilateral sciatic nerve transection to induce denervation of hindlimb muscles. The contralateral sham limb and nonsurgical mice (n = 5) were used as two different controls to account for potential crossover effects of denervation. We calculated gastrocnemius myofibrillar and collagen protein synthesis and breakdown assuming steady-state or using non-steady-state modelling. We measured RNA synthesis rates to further understand ribosomal turnover during atrophy.
RESULTS
Gastrocnemius mass was less in denervated muscle (137 ± 9 mg) compared with sham (174 ± 15 mg; P < 0.0001) or nonsurgical control (162 ± 5 mg; P < 0.0001). With steady-state calculations, fractional synthesis and breakdown rates (FSR and FBR) were lower in the denervated muscle (1.49 ± 0.06%/day) compared with sham (1.81 ± 0.09%/day; P < 0.0001) or nonsurgical control (2.27 ± 0.04%/day; P < 0.0001). When adjusting for change in protein mass, FSR was 4.21 ± 0.19%/day in denervated limb, whereas FBR was 4.09 ± 0.22%/day. When considering change in protein mass (k ), myofibrillar synthesis was lower in denervated limb (2.44 ± 0.14 mg/day) compared with sham (3.43 ± 0.22 mg/day; P < 0.0001) and non-surgical control (3.74 ± 0.12 mg/day; P < 0.0001), whereas rate of protein breakdown (k 1/t) was greater in denervated limb (0.050 ± 0.003) compared with sham (0.019 ± 0.001; P < 0.0001) and nonsurgical control (0.023 ± 0.000; P < 0.0001). Muscle collagen breakdown was completely inhibited during denervation. There was a strong correlation (r = 0.83, P < 0.001) between RNA and myofibrillar protein synthesis in sham but not denervated muscle.
CONCLUSIONS
We show conflicting results between steady- and non-steady-state calculations on myofibrillar protein synthesis and breakdown during periods of muscle loss. We also found that collagen accumulation was largely from a decrease in collagen breakdown. Comparison between sham and non-surgical control demonstrated a crossover effect of denervation on myofibrillar protein synthesis and ribosomal biogenesis, which impacts study design for unilateral atrophy studies. These considerations are important because not accounting for them can mislead therapeutic attempts to maintain muscle mass.
Topics: Animals; Male; Mice; Mice, Inbred C57BL; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy; Protein Biosynthesis
PubMed: 34418329
DOI: 10.1002/jcsm.12772 -
Hypertension (Dallas, Tex. : 1979) Oct 2020
Topics: Denervation; Humans; Hypertension; Kidney; Microdissection; Nervous System
PubMed: 32903105
DOI: 10.1161/HYPERTENSIONAHA.120.15834 -
High Blood Pressure & Cardiovascular... Aug 2020
Topics: Denervation; Humans; Kidney
PubMed: 32329030
DOI: 10.1007/s40292-020-00381-2 -
Journal of Orthopaedic Surgery and... May 2023Lumbar facet joint pain is a common disorder. The main symptom is chronic lumbar pain, which can reduce quality of life. Radiofrequency has often been used to treat...
BACKGROUND
Lumbar facet joint pain is a common disorder. The main symptom is chronic lumbar pain, which can reduce quality of life. Radiofrequency has often been used to treat lumbar facet joint pain. However, the effectiveness of this technique has been controversial. This study was conducted to compare the effectiveness of pulsed radiofrequency (PRF) and radiofrequency denervation (RD) for lumbar facet joint pain.
METHODS
One hundred and forty-two patients with lumbar facet joint pain were allocated to two treatment groups: PRF group (N = 72) and RD group (N = 70). Patients enrolled in the study were assessed using a visual analogue scale (VAS), Roland-Morris questionnaire (RMQ), Oswestry disability index (ODI) and Short-Form 36 (SF-36) questionnaire before therapy, 3 months and 12 months later.
RESULTS
There were no significant differences in VAS, RMQ score, ODI score and SF-36 score at 3 months (p > 0.05). Significant differences in pain control were observed in both groups at 12 months (3.09 ± 1.72 vs. 2.37 ± 1.22, p = 0.006). There was a significant difference in RMQ score (11.58 ± 3.58 vs. 8.17 ± 2.34, p < 0.001) and ODI score (43.65 ± 11.01 vs. 35.42 ± 11.32, p < 0.001) at 12 months. The total SF-36 score was higher in the RD group than in the PRF group at 12 months (58.45 ± 6.97 vs. 69.36 ± 6.43, p < 0.001). In terms of complications, skin numbness occurred in three patients. Mild pain such as burning and pinking at the puncture site in two patients. One patient experienced a decrease in back muscle strength and back muscle fatigue. These complications disappeared in 3 weeks without any treatment. There were no serious adverse events in the PRF group.
CONCLUSION
Radiofrequency is an effective and safe treatment option for patients with lumbar facet joint pain. RD could provide good and lasting pain relief, with significant improvement in lumbar function and quality of life at long-term follow-up.
Topics: Humans; Zygapophyseal Joint; Pulsed Radiofrequency Treatment; Quality of Life; Spinal Puncture; Low Back Pain; Arthralgia; Denervation; Treatment Outcome
PubMed: 37143095
DOI: 10.1186/s13018-023-03814-5 -
Clinical Research in Cardiology :... May 2021Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal...
Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.
BACKGROUND
Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.
OBJECTIVES
We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.
METHODS
Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety.
RESULTS
All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up.
CONCLUSIONS
Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.
Topics: Angiography; Animals; Cardiometabolic Risk Factors; Disease Models, Animal; Feasibility Studies; Follow-Up Studies; Hepatic Artery; Humans; Norepinephrine; Renal Artery; Swine; Sympathectomy; Time Factors
PubMed: 33635438
DOI: 10.1007/s00392-021-01814-1 -
Clinical Research in Cardiology :... Sep 2022In the wake of the controversy surrounding the SYMPLICITY HTN-3 trial and data from subsequent trials, this review aims to perform an updated and more comprehensive...
BACKGROUND
In the wake of the controversy surrounding the SYMPLICITY HTN-3 trial and data from subsequent trials, this review aims to perform an updated and more comprehensive review of the impact of renal sympathetic denervation on cardiac arrhythmias.
METHODS AND RESULTS
A systematic search was performed using the Medline, Scopus and Embase databases using the terms "Renal Denervation" AND "Arrhythmias or Atrial or Ventricular", limited to Human and English language studies within the last 10 years. This search yielded 19 relevant studies (n = 6 randomised controlled trials, n = 13 non-randomised cohort studies) which comprised 783 patients. The studies show RSD is a safe procedure, not associated with increases in complications or mortality post-procedure. Importantly, there is no evidence RSD is associated with a deterioration in renal function, even in patients with chronic kidney disease. RSD with or without adjunctive pulmonary vein isolation (PVI) is associated with improvements in freedom from atrial fibrillation (AF), premature atrial complexes (PACs), ventricular arrhythmias and other echocardiographic parameters. Significant reductions in ambulatory and office blood pressure were also observed in the majority of studies.
CONCLUSION
This review provides evidence based on original research that 'second generation' RSD is safe and is associated with reductions in short-term blood pressure and AF burden. However, the authors cannot draw firm conclusions with regards to less prominent arrhythmia subtypes due to the paucity of evidence available. Large multi-centre RCTs investigating the role of RSD are necessary to comprehensively assess the efficacy of the procedure treating various arrhythmias.
Topics: Atrial Fibrillation; Catheter Ablation; Humans; Kidney; Pulmonary Veins; Renal Insufficiency, Chronic; Sympathectomy; Treatment Outcome
PubMed: 34748053
DOI: 10.1007/s00392-021-01950-8 -
International Journal of Molecular... Mar 2023Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to...
Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to the activation and expansion of resident fibro/adipogenic progenitors (FAPs), i.e., multipotent stromal cells with myofibroblast potential. Using in vivo and in silico approaches, we revealed FAPs as a novel cell population that activates the transcriptional coregulators YAP/TAZ in response to skeletal muscle denervation. Here, we found that denervation induces the expression and transcriptional activity of YAP/TAZ in whole muscle lysates. Using the transgenic reporter mice to trace FAPs, we demonstrated that denervation leads to increased YAP expression that accumulates within FAPs nuclei. Consistently, re-analysis of published single-nucleus RNA sequencing (snRNA-seq) data indicates that FAPs from denervated muscles have a higher YAP/TAZ signature level than control FAPs. Thus, our work provides the foundations to address the functional role of YAP/TAZ in FAPs in a neurogenic pathological context, which could be applied to develop novel therapeutic approaches for the treatment of muscle disorders triggered by motoneuron degeneration.
Topics: Animals; Mice; Adipogenesis; Cell Differentiation; Denervation; Mice, Transgenic; Muscle, Skeletal
PubMed: 36982659
DOI: 10.3390/ijms24065585 -
JACC. Clinical Electrophysiology Mar 2022
Topics: Heart; Humans; Long QT Syndrome; Sympathectomy
PubMed: 35331423
DOI: 10.1016/j.jacep.2021.11.004 -
American Journal of Physiology. Cell... Aug 2021Muscle fiber denervation is a major contributor to the decline in physical function observed with aging. Denervation can occur through breakdown of the neuromuscular... (Review)
Review
Muscle fiber denervation is a major contributor to the decline in physical function observed with aging. Denervation can occur through breakdown of the neuromuscular junctions (NMJ) itself, affecting only that particular fiber, or through the death of a motor neuron, which can lead to a loss of all the muscle fibers in that motor unit. In this review, we discuss the muscle-nerve relationship, where signaling from both the motor neuron and the muscle fiber is required for maximal preservation of neuromuscular function in old age. Physical activity is likely to be the most important single factor that can contribute to this preservation. Furthermore, we propose that inactivity is not an innocent bystander, but plays an active role in denervation through the production of signals hostile to neuron survival. Investigating denervation in human muscle tissue samples is challenging due to the shared protein profile of regenerating and denervated muscle fibers. In this review, we provide a detailed overview of the key traits observed in immunohistochemical preparations of muscle biopsies from healthy, young, and elderly individuals. Overall, a combination of assessing tissue samples, circulating biomarkers, and electrophysiological assessments in humans will prove fruitful in the quest to gain more understanding of denervation of skeletal muscle. In addition, cell culture models represent a valuable tool in the search for key signaling factors exchanged between muscle and nerve, and which exercise has the capacity to alter.
Topics: Aging; Animals; Exercise; Humans; Muscle Denervation; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuromuscular Junction
PubMed: 34161153
DOI: 10.1152/ajpcell.00174.2021