Days Of Electrical Stimulation Research Articles

Electrical Ear Canal Stimulation as a Therapeutic Approach for Tinnitus-A Proof of Concept Study.

Background: Tinnitus-the perception of sound despite the absence of an external source-can be a debilitating condition for which there are currently no pharmacological remedies. Our proof of concept study focused on the immediate effects of non-invasive electrical stimulation through the ear canal on loudness and tinnitus-induced distress. In addition, we aimed to identify variables that may affect the simulation outcomes. Methods: Sixty-six patients (29 women and 37 men, mean age 54.4 ± 10.4) with chronic tinnitus were recruited to the tertiary referral hospital between December 2019 and December 2021. They underwent 10 min of electrical stimulation through the ear canal for three consecutive days. Visual analog scales measured loudness and tinnitus-induced distress immediately before and after stimulation. Results: After three days of electrical stimulation, tinnitus loudness decreased in 47% of patients, 45.5% reported no change, and 7.6% reported worsening. Tinnitus severity decreased in 36.4% of cases, 59.1% of patients reported no change, and 4.5% reported worsening. Women responded positively to therapy earlier than men. In addition, tinnitus distress decreased in patients with compensated tinnitus but not in those with uncompensated tinnitus. Finally, patients with bilateral tinnitus improved earlier than those with unilateral tinnitus, and the age of the patients did not influence the stimulation results. Conclusions: Our proof of concept study confirms the potential of non-invasive electrical stimulation of the ear as a promising screening approach to identifying patients for more advanced electrostimulation treatment, such as an extracochlear anti-tinnitus implant. These findings have practical implications for tinnitus management, offering hope for improved patient care.

Reason for the increased electroactivity of extracellular polymeric substances with electrical stimulation: Structural change of α-helix peptide of protein

Electroactivity is an important parameter to assess the ability of the extracellular polymeric substance (EPS) of microorganisms to participate in extracellular respiration. Many reports have found that the electroactivity of microbial sludge could be enhanced with electrical stimulation, but the reason remains unclear. The results of this study showed that the current generation of the three microbial electrolysis cells increased by 1.27–1.76 times during 49 days of electrical stimulation, but the typical electroactive microorganisms were not enriched. Meanwhile, the capacitance and conductivity of EPS of sludge after the electrical stimulation increased by 1.32–1.83 times and 1.27–1.32 times, respectively. In-situ FTIR analysis indicated that the electrical stimulation could lead to the polarization of amide groups in the protein, likely affecting the protein structure related to the electroactivity. Accordingly, the dipole moment of the α-helix peptide of protein of sludge increased from 220 D to 280 D after the electrical stimulation, which was conducive to electron transfer in the α-helix peptide. Moreover, the vertical ionization potential and ELUMO-EHOMO energy gap of the C-terminal in the α-helix peptide decreased from 4.43 eV to 4.10 eV and 0.41 eV to 0.24 eV, respectively, which indicated that the α-helix was easier to serve as the electron transfer site of electron hopping. These results meant that the enhancement of the dipole moment of the α-helix peptide unchoked the electron transfer chain of the protein, which was the main reason for the increased electroactivity of EPS protein.

Percutaneous Neuromodulation of the Brachial Plexus and Sciatic Nerve for the Treatment of Acute Pain Following Surgery: Secondary Outcomes From a Multicenter, Randomized, Controlled Pilot Study

ObjectivesWe recently reported that percutaneous peripheral nerve stimulation (PNS or “neuromodulation”) decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately. Materials and MethodsBefore surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other. ResultsFor brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations. ConclusionsAmbulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery.

Novel method to repair articular cartilage by direct reprograming of prechondrogenic mesenchymal stem cells

Age-related cartilage loss is worsened by the limited regenerative capacity of chondrocytes. The role of cell-based therapies using mesenchymal stem cells is gaining interest. Adipose tissue-derived mesenchymal stem cells (ADSCs) are an attractive source to generate the optimal number of chondrocytes required to repair a cartilage defect and regenerate hyaline articular cartilage. Here, we report an outstanding technique to prepare chondrocytes for cartilage repair using canine ADSCs. We hypothesized that external electrical fields promote prechondrogenic condensation without requiring genetic modifications or exogenous factors. We analyzed the effect of electrical stimulation (ES) on the differentiation of ADSC micromass into chondrocytes. Highly compact structures were formed within 3 days of ES of canine ADSC micromass. The expression of type I collagen gene was abolished in these cells compared with that in control micromass cultures and monolayer cultures. We further found that ES enhanced the production of proteoglycan, a highly produced extracellular matrix component in chondrocytes. Additionally, single-cell RNA sequencing analysis showed that canine ADSC micromass undergoing ES developed a prechondrogenic cell aggregation, suggesting their metabolic conversion, biogenesis, and calcium ion change. Collectively, our findings demonstrate the capacity of ES to drive the chondrogenesis of ADSCs in the absence of exogenous factors and confirm its commercial potential as a budget-friendly therapy for the repair of cartilage defects.

Microfluidics embedded with microelectrodes for electrostimulation of neural stem cells proliferation

The regeneration of the injured nerve and recovery of its function have brought attention in the medical field. Electrical stimulation (ES) can enhance the cellular biological behavior and has been widely studied in the treatment of neurological diseases. Microfluidic technology can provide a cell culture platform with the well-controlled environment. Here a novel microfluidic/microelectrode composite microdevice was developed by embedding the microelectrodes to the microfluidic platform, in which microfluidics provided a controlled cell culture platform, and ES promoted the NSCs proliferation. We performed ES on rat neural stem cells (NSCs) to observe the effect on their growth, differentiation, proliferation, and preliminary explored the ES influence on cells in vitro. The results of immunofluorescence showed that ES had no significant effect on the NSCs specific expression, and the NSCs specific expression reached 98.9% ± 0.4% after three days of ES. In addition, ES significantly promoted cell growth and the cell proliferation rate reached 49.41%. To conclude, the microfluidic/microelectrode composite microdevice can play a positive role in the nerve injury repair and fundamental research of neurological diseases.

Chondrogenic potential of animal adult stem cells through electrical stimulation

Background & Aim Mesenchymal stem cells (MSCs) represent an appealing alternative cell source for cartilage repair. There are studies that induce differentiation into cartilage cells by treating the growth factors in MSCs or altering the properties of MSCs by genetic modification. Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. Use of low-frequency ES for therapeutic purposes has been increasing during the last decades. In this study, we exposed equine adipose tissue-derived MSCs (eAD-MSCs) to ES and assessed changes in the chondrogenic differentiation potential. Methods, Results & Conclusion The cells obtained from equine adipose tissue attached to culture plates and expanded in vitro. Flow cytometric analysis at third passage indicated that the cells were strongly positive for CD44, CD90, and CD105, but negative for CD13, CD34, and CD45. ES was applied to eAD-MSCs cultured under condition of high-density micro-mass under ES of 10 V/cm, with duration of 10 ms and a frequency of 2.0 Hz for three days. We compared chondrogenic differentiation potential of non-ES and ES condition. Expression levels of chondrogenic potential-related markers were examined by quantitative real-time RT-PCR. Articular cartilage is divided into a hyaline cartilage layer and a fibrous cartilage layer. Osteoarthritis (OA) is a disease caused by the natural degeneration of cartilage layer. From the beginning, OA of the middle stage leads to damage of the hyaline cartilage, and damage of the fibrous cartilage at the last stage. We observed the differentiation potential of eAD-MSCs into chondrocytes by specific ES in absence of exogenous growth factors. Gene expression of chondrogenic markers such as type II collagen (COL2A1), Aggrecan, and Sox9 was analyzed at 3 days of ES. Based on the mechanism that chondrocyte formation in articular cavity starts from the aggregation of cells, we observed the differentiation potential of eAD-MSCs into chondrocytes by specific ES in absence of exogenous growth factors. Therefore, this study might contribute to the differentiation of stem cells into cartilage cells by inducing pre-chondrogenic condensation under specific ES.

Effects of Intermittent Calf Muscle Electrical Stimulation on Walking Capacity in Claudicants Living with Type 2 Diabetes.

First-line therapy for diabetic patients presenting with intermittent claudication includes supervised exercise programs to improve walking distance. However, exercise comes with a variety of barriers and may be contraindicated in certain conditions. The aim of this study was to evaluate whether calf muscle electrostimulation improves claudication distance. A prospective, one-group, pretest-posttest study design was used on 40 participants living with type 2 diabetes mellitus, peripheral artery disease (ankle brachial pressure index, <0.90), and calf muscle claudication. Calf muscle electrostimulation of varying frequencies (1-250 Hz) was prescribed on both limbs for 1-hour daily sessions for 12 consecutive weeks. The absolute claudication distance (ACD) was measured at baseline and after the intervention. The recruited cohort (30 men and ten women; mean age, 71 years; mean ankle brachial pressure index, 0.70) registered a mean ± SD baseline ACD of 333.71 ± 208 m. After a mean ± SD of 91.68 ± 6.23 days of electrical stimulation, a significant mean ± SD increase of 137 ± 136 m in the ACD (P = .001, Wilcoxon signed rank test) was registered. Improvement was found to be sex independent, but age was negatively correlated with proportion of improvement (r = -0.361; P = .011, Pearson correlation test). Electrical stimulation of varying frequencies on ischemic calf muscles significantly increased the maximal walking capacity in claudicants with type 2 diabetes. This therapeutic approach should be considered in patients with impaired exercise tolerance or as an adjunct treatment modality.

Hydrogel Microchambers Integrated with Organic Electrodes for Efficient Electrical Stimulation of Human iPSC-Derived Cardiomyocytes.

A hydrogel-based microchamber with organic electrodes for efficient electrical stimulations of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is described. The microchamber is made from molecularly permeable, optically transparent, and electrically conductive polyvinyl alcohol (PVA) hydrogel and highly capacitive carbon electrode modified with poly(3,4-ethylenedioxythiophene) (PEDOT). Spheroids of hiPSC-CMs are cultured in microchambers, and electrically stimulated by the electrode for maturation. The large interfacial capacitance of the electrodes enables several days of electrical stimulation without generation of cytotoxic bubbles even when the electrodes are placed near the spheroids. The spheroids can be cultivated in the closed microchambers because of the permeated nutrients through the hydrogel, thus the spheroids are stably addressable and the culture medium around the sealed microchambers can be simply exchanged. Synchronized beating of the spheroids can be optically analyzed in situ, which makes it possible to selectively collect electrically responsive cells for further use. As the hydrogel is electrically conductive, the amount of electrical charge needed for maturing the spheroids can be reduced by configuring electrodes on the top and the bottom of the microchamber. The bioreactor will be useful for efficient production of matured hiPSC-CMs for regenerative medicine and drug screening.

Ascl1 Regulates Electric Field-Induced Neuronal Differentiation Through PI3K/Akt Pathway

Directing differentiation of neural stem/progenitor cells (NSCs/NPCs) to produce functional neurons is one of the greatest challenges in regenerative medicine. Our previous paper has confirmed that electrical stimulation has a high efficiency of triggering neuronal differentiation by using isolated filum terminale (FT)-derived NPCs. To further clarify the intrinsic molecular mechanisms, protein–protein interaction (PPI) network analysis was applied to pinpoints novel hubs in electric field (EF)-induced neuronal differentiation. In this study, siRNA transfection of Achaete-scute homolog 1 (Ascl1) in NPCs or NPCs was followed by direct current stimulation at 150 mV/mm. Neuronal differentiation rate and protein expression level were analyzed after 7 or 14 days of electrical stimulation. The data showed that the expression level of Ascl1 was enhanced by electrical stimulation and positively correlated to EF strength. Moreover, we identified that the expression of Ascl1 positively regulated neuronal differentiation of NPCs and can be up-regulated by EF-stimulation through the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Therefore, this study provides new insights into the role of Ascl1 and its relevant PI3K/Akt pathway in regulating of EF-induced neuronal differentiation and pointed out that continuous expression of Ascl1 in NPCs is required for EF-induced neuronal differentiation.

The effectiveness of electrical stimulation on muscle tone, elasticity and stiffness of gastrocnemius muscle in children with spastic cerebral palsy

Introduction/Background The aim of this study was to demonstrate the therapeutic effectiveness of electrical stimulation on muscle tone, elasticity and stiffness in children with spastic cerebral palsy. Material and method Thirty-one lower extremities of 18 patients with spastic cerebral palsy (5 diplegic, 8 quadriplegic and 5 hemiplegic) were evaluated. Biomechanical measurements of gastrocnemius muscle were performed using a myotonometry device. The MyotonPro was used to measure the muscle tone, elasticity and stiffness of the gastrocnemius muscle (medial and lateral parts) on bilateral sides of the patients with diplegic/quadriplegic cerebral palsy and from the paretic side of the patients with hemiplegic cerebral palsy. Patients were treated for five days of electrical stimulation (frequency of 50 Hz, pulse duration 300 ms, ramp of 0,5 ms, on:off time 5 s:5 s, session time of 30 minutes) which was applied on the gastrocnemius muscle aiming for the management of spasticity. The measurements were repeated after the fifth session. Results The mean age of the patients were 6.44 ± 3.6 (2.5–13). The mean Gross Motor Function Classification System level of the patients were 3.11 ± 1.6 (1–5) and Ashworth scale were 2.06 ± 0.75 (1–3). The muscle tone and stiffness of medial and lateral gastrocnemius muscle decreased significantly (P Conclusion Our results suggest that electrical stimulation for the treatment of spasticity had improvements on muscle tone, elasticity and stiffness of spastic cerebral palsy patients. And MyotonPro can be used to measure the effects of treatment in spasticity.

Advanced Functional Materials Solutions to Engineering the Neural Interface

Advanced Functional Materials Solutions to Engineering the Neural Interface

Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function.

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.

Potency of endothelial progenitor cells compared to bone marrow mononuclear cells in the restoration of angiogenesis

Bone‐marrow mononuclear cells (BMMCs) have been shown to promote angiogenesis, and clinical trials suggest BMMC‐based cell therapy may be feasible for treating ischemic disease. However, recent data suggests that the presence of underlying disease states may affect the benefit of autologous BMMC‐based therapy. We previously demonstrated that direct delivery of BMMCs from SS/Mcwi rat donors failed to rescue angiogenesis in the angiogenesis impaired SS/Mcwi rat, while replacement of chromosome 13 derived from the Brown Norway rat (SS‐ 13BN/Mcwi) rat restored the angiogenic competency of BMMCs in the SS/Mcwi recipients. In this study, we performed a direct comparison of the generally pro‐angiogenic endothelial progenitor cells (EPCs) isolated from BMMCs of either SS/Mcwi or SS‐ 13BN/Mcwi donor rats. EPCs were injected into the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of electrical stimulation. There were no differences in the angiogenic potential of EPCs from SS‐13BN/Mcwi compared to SS/Mcwi rats. Direct injection of as few as five‐hundred EPCs was sufficient to restore angiogenesis in SS/Mcwi recipients. SS‐13BN/Mcwi EPCs were slightly more potent than SS/Mcwi EPCs in restoring the response. These data suggest that EPCs provide a more viable therapeutic approach than BMMCs to treat a variety of ischemic diseases.

Neuromuscular electrical stimulation improves GLUT-4 and morphological characteristics of skeletal muscle in rats with heart failure

Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotrophy, 20 days of ES led to their recovery (P < 0.0001). In both groups submitted to ES, there was an increase in muscle vessel density (P < 0.04). Additionally, heart failure determined a 49% reduction in GLUT-4 protein content (P < 0.03), which was recovered by ES (P < 0.01). In heart failure, ES improves morphological changes and raises GLUT-4 content in skeletal muscle.

Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis

Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction has been reported, leading to poor cell engraftment and a failure of tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and that this effect is related to a dysregulation of the renin angiotensin system (RAS) that is normalized by the replacement of chromosome 13 derived from the Brown Norway rat (SS-13(BN)/Mcwi consomic rats). The present study explored bone marrow-derived endothelial cell (BM-EC) function in the SS/Mcwi rat and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS-13(BN)/Mcwi; SS/Mcwi rats infused with saline or ANG II (3 ng kg(-1) min(-1)). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of ES. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, BMC isolated from SS-13(BN)/Mcwi and SS/Mcwi rats infused with ANG II effectively restored the angiogenesis response in the SS/Mcwi recipient. Furthermore, ANG II infusion increased the capacity of BM-EC to induce endothelial cell tube formation in vitro and slightly increased VEGF protein expression. This study suggests that dysregulation of the RAS in the SS/Mcwi rat contributes to impaired BM-EC function and could impact the angiogenic therapeutic potential of BMC.

Role of the Renin Angiotensin System on Bone Marrow‐Derived Stem Cell Function and its Impact on Skeletal Muscle Angiogenesis After Electrical Stimulation

Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat ischemic disease. However, BMC dysfunction has been reported in several conditions, leading to poor cell engraftment and failure in tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and this effect seems to be related to an impaired regulation in the renin angiotensin system (RAS). The present study explored the role of the RAS on BMC function and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS‐13BN/Mcwi; SS/Mcwi rats infused with saline or ANGII (3 ng.kg‐1.min‐1). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. After 7 days of ES, unstimulated and stimulated muscles were harvested and the vessel density was evaluated. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, cells isolated from SS‐13BN/Mcwi consomic rats as well as from SS/Mcwi rats infused with ANGII showed a significant increase in vessel density after 7 days of ES. This study suggests that an impaired RAS regulation may be associated with a significant BMC dysfunction and have profound effects on the angiogenesis response induced by ES in SS/Mcwi rats. (Support NIH HL‐29587, N01 HV‐28182).

Suppression of natural killer cell cytotoxicity following chronic electrical stimulation of the ventromedial hypothalamic nucleus in rats

In our previous study we found that chronic electrical stimulation of the lateral hypothalamus (LH) enhances and its lesion suppresses natural killer cell cytotoxicity (NKCC) and a large granular lymphocyte (LGL) number in conscious, freely behaving rats. Since the ventromedial nucleus of the hypothalamus (VMH) is regarded as behaviorally and physiologically opposite to LH, in our present study we investigated whether this antagonism also holds for the immune functions. Chronic electrical VMH stimulation effect on 1) immune parameters: both spleen and blood NKCC (chromium release assay and single-cell agarose assay) and the number of large granular lymphocytes (LGL; a morphological method), and 2) endocrine parameters: immunosuppressive—corticosterone (COR) and testosterone (TST) and immunostimulative—growth hormone (GH) and prolactin (PRL) plasma levels (RIA) was assessed. Twenty-one days of electrical stimulation of VMH caused significant decrease in both spleen and blood NKCC at the population level (chromium release assay) but not at the single cell level (agarose assay) with a simultaneous fall in the LGL number. Rats responding to the VMH stimulation with behavioral inactivation (BIN) showed a significantly lower depression of NKCC and LGL number than those responding with an aversive reaction (AVE). Depression of NKCC coexisted with various hormonal changes: increase of PRL, increase (AVE) or fall (BIN) of COR, decrease of GH (BIN), and increase of TST (VMH-stimulated and VMH-sham). There were significant differences in all measured plasma hormones between BIN and AVE groups. The results obtained indicate that VMH decreases cell-mediated immune response, represented by NK cell activity. The immunosuppressive effect is dependent on the behavioral outcome of VMH stimulation (BIN/AVE) rather than tested endocrine variables. Moreover, the present results indicate that the VMH and LH are antagonistically engaged in the regulation of NK cell cytotoxicity.

Reliability of the biceps brachii M-wave

BackgroundThe peak-to-peak (P-P) amplitude of the maximum M-wave and the area of the negative phase of the curve are important measures that serve as methodological controls in H-reflex studies, motor unit number estimation (MUNE) procedures, and normalization factors for voluntary electromyographic (EMG) activity. These methodologies assume, with little evidence, that M-wave variability is minimal. This study therefore examined the intraclass reliability of these measures for the biceps brachii.MethodsTwenty-two healthy adults (4 males and 18 females) participated in 5 separate days of electrical stimulation of the musculocutaneous nerve supplying the biceps brachii muscle. A total of 10 stimulations were recorded on each of the 5 test sessions: a total of fifty trials were used for analysis. A two-factor repeated measures analysis of variance (ANOVA) evaluated the stability of the group means across test sessions. The consistency of scores within individuals was determined by calculating the intraclass correlation coefficient (ICC). The variance ratio (VR) was then used to assess the reproducibility of the shape of the maximum M-wave within individual subjects.ResultsThe P-P amplitude means ranged from 12.62 ± 4.33 mV to 13.45 ± 4.07 mV across test sessions. The group means were highly stable. ICC analysis also revealed that the scores were very consistent (ICC = 0.98). The group means for the area of the negative phase of the maximum M-wave were also stable (117 to 126 mV·ms). The ICC analysis also indicated a high degree of consistency (ICC = 0.96). The VR for the sample was 0.244 ± 0.169, which suggests that the biceps brachii maximum M-wave shape was in general very reproducible for each subject.ConclusionThe results support the use of P-P amplitude of the maximum M-wave as a methodological control in H-reflex studies, and as a normalization factor for voluntary EMG. The area of the negative phase of the maximum M-wave is both stable and consistent, and the shape of the entire waveform is highly reproducible and may be used for MUNE procedures.

Renin Gene Transfer Restores Angiogenesis and VEGF Expression in Dahl S Rats

P204 To evaluate the importance of the renin angiotensin system (RAS) in VEGF expression and angiogenesis in skeletal muscle, we compared the angiogenic response to electrical stimulation in congenic strains of SS/Jr/Hsd rats using a complementation test design. We have previously demonstrated that both increases in VEGF expression and angiogenesis induced by electrical stimulation of skeletal muscle were absent in inbred Dahl S rats having a wildtype renin allele (S/ren ss ). In contrast, the congenic S/ren rr in which a 10 cM segment of chromosome 13 containing the normally functioning salt resistant renin allele was transferred onto the Dahl S background, exhibit the expected changes in renin. In the present study we investigate the effects of electrical stimulation on VEGF expression and angiogenesis in these rats. Congenic S/ren rr and S/ren ss rats, fed a 0.4% salt diet were surgically prepared by chronic implantation of an electrical stimulator. Another group of S/ren rr rats was treated with lisinopril, 2 days before the surgery and throughout the stimulation protocol. Rats without any drug treatment were used as control. The right tibialis anterior (TA) and extensor digitorum longus (EDL) were stimulated (10 Hz, 0.3 ms duration) for 8 hours per day for 7 days. The contralateral muscles served as controls. Western blot analysis was performed to identify VEGF protein expression in these muscles. Seven days of electrical stimulation of the skeletal muscles produced no change in vessel density of S/ren ss (Δ=5.50 ± 3.8 % and 8.14 ± 2.0 % for EDL and TA respectively). Transfer of the resistant renin allele (S/ren rr ) restored the angiogenic response (Δ=16% and 30% for EDL and TA, respectively) despite a significantly higher blood pressure (113.5 ± 2.25 mmHg and 148.67 ± 1.12 mmHg for S/ren ss and S/ren rr , respectively). Blockade of the RAS in S/ren rr restored the phenotype observed in the S/ren ss (Δ=1.46% and 1.9% to EDL and TA, respectively, p rr . These results demonstrate that RAS plays an important role in the regulation of VEGF expression and angiogenesis in skeletal muscle.

Renin Gene Transfer Restores Angiogenesis and VEGF Expression in Dahl S Rats

P204 To evaluate the importance of the renin angiotensin system (RAS) in VEGF expression and angiogenesis in skeletal muscle, we compared the angiogenic response to electrical stimulation in congenic strains of SS/Jr/Hsd rats using a complementation test design. We have previously demonstrated that both increases in VEGF expression and angiogenesis induced by electrical stimulation of skeletal muscle were absent in inbred Dahl S rats having a wildtype renin allele (S/ren ss ). In contrast, the congenic S/ren rr in which a 10 cM segment of chromosome 13 containing the normally functioning salt resistant renin allele was transferred onto the Dahl S background, exhibit the expected changes in renin. In the present study we investigate the effects of electrical stimulation on VEGF expression and angiogenesis in these rats. Congenic S/ren rr and S/ren ss rats, fed a 0.4% salt diet were surgically prepared by chronic implantation of an electrical stimulator. Another group of S/ren rr rats was treated with lisinopril, 2 days before the surgery and throughout the stimulation protocol. Rats without any drug treatment were used as control. The right tibialis anterior (TA) and extensor digitorum longus (EDL) were stimulated (10 Hz, 0.3 ms duration) for 8 hours per day for 7 days. The contralateral muscles served as controls. Western blot analysis was performed to identify VEGF protein expression in these muscles. Seven days of electrical stimulation of the skeletal muscles produced no change in vessel density of S/ren ss (Δ=5.50 ± 3.8 % and 8.14 ± 2.0 % for EDL and TA respectively). Transfer of the resistant renin allele (S/ren rr ) restored the angiogenic response (Δ=16% and 30% for EDL and TA, respectively) despite a significantly higher blood pressure (113.5 ± 2.25 mmHg and 148.67 ± 1.12 mmHg for S/ren ss and S/ren rr , respectively). Blockade of the RAS in S/ren rr restored the phenotype observed in the S/ren ss (Δ=1.46% and 1.9% to EDL and TA, respectively, p&lt;0.05). In addition, increases in VEGF expression to electrical stimulation were observed only in S/ren rr . These results demonstrate that RAS plays an important role in the regulation of VEGF expression and angiogenesis in skeletal muscle.