Bradyarrhythmia in a marathonist: Cardiac vagal denervation as alternative treatment.

Although not routinely used, cardioneuroablation or modulation of the cardiac autonomic nervous system has been proposed as an alternative approach to treat young individuals with enhanced vagal tone and significant atrioventricular (AV) disturbances. We report the case of a 42-year-old athlete with prolonged ventricular pauses associated with sinus bradycardia and paroxysmal episodes of AV block (maximum of 6.6 s) due to enhanced vagal tone who was admitted to our hospital for pacemaker implantation. Cardiac magnetic resonance and stress test were normal. Although he was asymptomatic, safety concerns regarding possible neurological damage and sudden cardiac death were raised, and he accordingly underwent electrophysiological study (EPS) and cardiac autonomic denervation. Mapping and ablation were anatomically guided and radiofrequency pulses were delivered at empirical sites of ganglionated plexi. Modulation of the parasympathetic system was confirmed through changes in heart rate and AV nodal conduction properties associated with a negative cardiac response to atropine administration. After a follow-up of nine months, follow-up 24-hour Holter revealed an increase in mean heart rate and no AV disturbances, with rare non-significant ventricular pauses, suggesting that this technique may become a safe and efficient procedure in this group of patients.

Renal sympathetic denervation in resistant hypertension: The association between vitamin D and positive early response in systolic blood pressure.

AIMS AND OBJECTIVES: Vitamin D deficiency is a common finding and there is a suggested association with hypertension. Resistant hypertension is a clinical problem observed in 5-30% of hypertensive patients. Renal denervation (RDN) has been used for patients with resistant hypertension and has proven to lower blood pressure. Our primary goal was to assess the vitamin D serum concentration as a predictor of blood pressure response to RDN in highly selected patients. METHODS: This prospective, nonrandomized, single-center study included 24 patients treated with RDN. Based on their one-year response after RDN, patients were classified as responders or non-responders at six months or at 12 months. RESULTS: The median follow-up was 52 months (range, 14-91 months). After RDN, 17 patients (70.8%) had a reduction >5 mmHg in the mean systolic blood pressure, at the first six months of follow-up. At 12 months, 20 patients (83.3%) were responders. Vitamin D levels at baseline (15.1±4.8 vs. 24.2±8.8 ng/ml) and at six months (16.6±7.2 vs. 25±9.2 ng/ml) were lower in early non-responders compared to early responders (p=0.008), without significant variation during follow-up. Even though Vitamin D levels were lower in the total responder's group, no statistically significant differences were found (p=ns). CONCLUSION: In patients with resistant hypertension, low vitamin D concentrations were associated with an absence of early response to RDN.

A new experimental model of intrinsic denervation in ileum from wistar rats through intramural microinjections of benzalkonium chloride / Um novo modelo experimental de desnervação intrínseca em íleo de ratos wistar através de micro injeções intramurais de cloreto de benzalcônio

Extensive literature is available about the intrinsic denervation of segments of the digestive tube through the application of CB in the serosa of the viscera. However, this technique has some disadvantages like causing peritonitis, flanges and high mortality, limiting its use in humans. The aim of the present study was to evaluate the feasibility of benzalkonium chloride (CB) to induce intrinsic chemical denervation, through applications of CB in the intramural ileum of wistar rats, as well as deepen the knowledge about the evolution of neuronal injury caused in the process. We used 40 rats, divided into two groups (control-GC and benzalkonium-GB) of 20 animals each, divided into four sub-groups according to the time of postoperative assessment of 24, 48 hours, 30 and 90 days. The animals were submitted to intramural microinjections of sterile saline solution 0.9% (GC) or benzalkonium chloride (GB) in ileal portion, and subsequent histopathological analysis and immunohistochemistry for evaluation of neuronal injury. A significant decrease (p<0.05) was found of the neuronal myenteric count over time in groups, GB3, GB4 and GB2. The specific positive immunolabeling for H2AX and Caspase-3 confirmed the results obtained in the histopathological evaluation, denoting the ignition of irreversible cell injury in 24 hours, evolving into neuronal apoptosis in 48 hours after application of the CB 0.3%. Under the conditions in which this work was conducted, it can be concluded that the application of CB 0.3% by means of microinjections intramural in the ileal wall is able to induce intrinsic chemical denervation of the diverticulum of wistar rats and that the main mechanism of neuronal death is induction of apoptosis.(AU)

Existe vasta literatura sobre a desnervação intrínseca de segmentos do tubo digestório através da aplicação de CB na serosa da víscera. Entretanto, essa técnica tem a desvantagem de causar peritonite, formação de bridas e alta mortalidade, não sendo factível para eventuais utilizações em humanos. O objetivo do presente estudo foi avaliar a viabilidade do Cloreto de benzalcônio (CB) induzir desnervação química intrínseca, por meio de aplicações intramurais em íleo de ratos wistar, além de aprofundar o conhecimento sobre a evolução da lesão neuronal causada neste processo. Foram utilizados 40 ratos, distribuídos em dois grupos (controle- GC e benzalcônio- GB) de 20 animais cada, subdivididos em quatro subgrupos de acordo com o tempo de avaliação pós-operatória de 24, 48 horas, 30 e 90 dias. Os animais foram submetidos à microinjeções intramurais de solução salina estéril 0,9% (GC) ou de cloreto de benzalcônio (GB) em porção ileal, e posterior análise histopatológica e imuno-histoquímica, para avaliação da lesão neuronal. Houve diminuição significativa (p<0,05) na contagem neuronal mientérica ao longo do tempo nos grupos GB2, GB3 e GB4. A imunomarcação específica positiva para H2AX e Caspase-3 confirmou os resultados obtidos na avaliação histopatológica, denotando início da lesão celular irreversível em 24 horas, evoluindo para apoptose neuronal em 48 horas após a aplicação do CB 0,3%. Nas condições em que este trabalho foi conduzido, é possível concluir que a aplicação de CB 0,3% por meio de microinjeções intramurais na parede ileal é capaz de induzir desnervação química intrínseca da porção ileal de ratos wistar e que o principal mecanismo de morte neuronal é a indução de apoptose.(AU)

Caracterização farmacológica da desnervação e reinervação simpática do ducto deferente de rato

The vas deferens of rat (DDR) has rich sympathetic innervation, being the main ATP noradrenaline and mediators involved in neurotransmission in the organ. Several studies have shown that in the DDR surgically denervated changes occur in tissue contraction. However, there are scarce studies that characterized these changes and followed for a longer time to consider the period of reinnervation of the fabric. This study set out to do in DDR surgically denervated, a temporal analysis of the changes in contractile ability of starting the study 4 days after surgery and reinnervation process for 84 days after the procedure, in order to establish new parameters indicative of reinnervation of the organ. For this the DDR will be denervated according to the technique described by Kasuya et al. (1969), the animals were anesthetized with ketamine and Xylazina, then an incision was made in the region above pubis, exposing the seminal vesicle and the DDR. With the help of tweezers, the nerve and artery that travels along the vas deferens of rat were separated from the organ for about 1 cm, a small amount of phenol 5% was applied in this region, and the abdominal wall was sutured. Non-operated animals were used as controls. After the procedure the mice were housed in cage and taken to the biologist to be used in experiments. In different days after the procedures (4, 7, 14, 21, 28, 56 and 84) the animals were euthanized in CO2 Chamber the DDRs removed, cleaned and assembled in isolated organ equipment where they were subjected to the action of KCl and high frequency electric stimulus. We observed that there was no change in the areas of the contraction curves of the denervated animals in comparison with those of the control group. . The data indicate that the contractility of the organ is not affected by the surgical denervation of the sympathetic component of the organ, which leads us to suggest that there should be a compensation of the contractile machinery in order to maintain the functionality of the organ, even under conditions of sympathetic neurotransmission failure.

O ducto deferente de rato (DDR) possui rica inervação simpática, sendo noradrenalina e ATP os principais mediadores envolvidos na neurotransmissão do tecido. Vários trabalhos já mostraram que no DDR desnervado cirurgicamente ocorrem alterações na contração do tecido. Entretanto, são escassos os estudos que caracterizaram essas mudanças e principalmente que acompanharam por um tempo mais longo que considerasse o período de reinervação do tecido. O presente trabalho se propôs a fazer, em DDR desnervado cirurgicamente, uma análise temporal das alterações na capacidade contrátil do órgão iniciando o estudo 4 dias após a cirurgia e acompanhando o processo de reinervação por 84 dias após o procedimento, a fim de estabelecer novos parâmetros indicativos da reinervação do órgão. Para isto os DDR foram desnervados segundo a técnica descrita por Kasuya e colaboradores (1969), os animais foram anestesiados com Ketamina e Xylazina em seguida foi feita uma incisão na região supra púbica, expondo a vesícula seminal e o DDR, com a ajuda de uma pinça, o nervo e a artéria que correm junto ao ducto deferente de rato foram separados do órgão por cerca de 1 cm, uma pequena quantidade de fenol 5% foi aplicada nesta região, sendo a parede abdominal suturada a seguir. Animais não operados foram utilizados como controles. Após o procedimento os ratos foram novamente alojados em gaiola e levados ao biotério até serem utilizados nos experimentos. Nos diferentes dias após os procedimentos (4, 7, 14, 21, 28, 56 e 84) os animais foram eutanasiados em câmara de CO2 os DDRs retirados, limpos e montados no equipamento de órgão isolado quando foram submetidos à ação do KCl e estímulo elétrico de alta frequência. Observamos que não houve alteração nas áreas das curvas de contração dos animais desnervados em comparação com aqueles do grupo controle. Os dados indicam que a contratilidade do órgão não é afetada pela desnervação cirúrgica do componente simpático do órgão, o que nos leva a sugerir que deva existir uma compensação da maquinaria contrátil a fim de manter a funcionalidade do órgão, mesmo em condições de falha da neurotransmissão simpática.

Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation.

INTRODUCTION: Sympathetic renal denervation (RDN) was developed as a treatment for the management of patients with resistant hypertension. This procedure may have a positive impact on hypertension-related target organ damage, particularly renal disease, but the evidence is still limited. OBJECTIVE: To assess the impact of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up. METHODS AND RESULTS: From a single-center prospective registry including 65 patients with resistant hypertension undergoing renal denervation, 31 patients with complete baseline and 12-month follow-up blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) and ACR were included in the present study. Mean age was 65±7 years, 52% were female, most (90%) had been diagnosed with hypertension for more than 10 years, 71% had type 2 diabetes and 33% had vascular disease in at least one territory. Mean estimated glomerular filtration rate was 73.6±25.1 ml/min/1.73 m2 and 15 patients (48%) had an ACR >30 mg/g. After 12 months, 22 patients were considered BP responders (73%). ACR decreased significantly from a median of 25.8 mg/g (interquartile range [IQR] 9.0-574.0 mg/g) to 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007). When the results were split according to systolic BP responder status on ABPM, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in the non-responder subgroup (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345). CONCLUSIONS: Besides significant reductions in blood pressure (both office and 24-h ABPM), renal denervation was associated with a significant reduction in ACR, a recognized marker of target organ damage.

Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

INTRODUCTION: Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. OBJECTIVE: To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). METHODS: Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. RESULTS: The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). CONCLUSION: RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance.

Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?

Hypertension is one of the most common chronic clinical problems encountered by physicians. The prevalence of resistant hypertension is estimated at 9% in the US. Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events, hence the need for greater efforts in improving the treatment of hypertension. The renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release and alterations in renal blood flow. The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation; a potential treatment option for resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15 and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension.

Renal denervation for resistant hypertension.

There is a marked contrast between the high prevalence of hypertension and the low rates of adequate control. A subset of patients with suboptimal blood pressure control have drug-resistant hypertension, in the pathophysiology of which chronic sympathetic hyperactivation is significantly involved. Sympathetic renal denervation has recently emerged as a device-based treatment for resistant hypertension. In this review, the pathophysiological mechanisms linking the sympathetic nervous system and cardiovascular disease are reviewed, focusing on resistant hypertension and the role of sympathetic renal denervation. An update on experimental and clinical results is provided, along with potential future indications for this device-based technique in other cardiovascular diseases.

Renal denervation in patients with resistant hypertension: six-month results.

INTRODUCTION: Increased activation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension (HTN). Catheter-based renal denervation (RDN) was recently developed for the treatment of resistant HTN. AIM: To assess the safety and efficacy of RDN for blood pressure (BP) reduction at six months in patients with resistant HTN. METHODS: In this prospective registry of patients with essential resistant HTN who underwent RDN between July 2011 and May 2013, the efficacy of RDN was defined as ≥ 10 mm Hg reduction in office systolic blood pressure (SBP) six months after the intervention. RESULTS: In a resistant HTN outpatient clinic, 177 consecutive patients were evaluated, of whom 34 underwent RDN (age 62.7 ± 7.6 years; 50.0% male). There were no vascular complications, either at the access site or in the renal arteries. Of the 22 patients with complete six-month follow-up, the response rate was 81.8% (n=18). The mean office SBP reduction was 22 mm Hg (174 ± 23 vs. 152 ± 22 mm Hg; p<0.001) and 9 mm Hg in diastolic BP (89 ± 16 vs. 80 ± 11 mm Hg; p=0.006). The number of antihypertensive drugs (5.5 ± 1.0 vs. 4.6 ± 1.1; p=0.010) and pharmacological classes (5.4 ± 0.7 vs. 4.6 ± 1.1; p=0.009) also decreased significantly. Of the 24-hour ambulatory BP monitoring and echocardiographic parameters analyzed, there were significant reductions in diastolic load (45 ± 29 vs. 27 ± 26%; p=0.049) and in left ventricular mass index (174 ± 56 vs. 158 ± 60 g/m(2); p=0.014). CONCLUSION: In this cohort of patients with resistant HTN, RDN was safe and effective, with a significant BP reduction at six-month follow-up.

Effects of long-term fluoxetine treatment on adrenergic plasticity in rat vas deferens

Chronic antidepressant administration increases neurotrophin levels in the central and peripheral nervous system, leading to an increase of neuronal sprouting, reestablishment of neural networks and neurotransmitter levels. Injured peripheral nerves regenerate at very slow rates. However, the recovery of the hypogastric nerve in rodents after injury is significantly improved with neurotrophin administration. Accordingly, our goal was to determine whether treatment with the antidepressant fluoxetine affects catecholamine levels and neuronal function, after surgical denervation of the rat vas deferens. Noradrenaline levels in the denervated vas deferens were higher in fluoxetine-treated animals than in the vehicle-treated group, as measured by high performance liquid chromatography. In functional studies of smooth muscle contraction, the responses induced by phenylephrine or ATP, as well as pre-synaptic α2-adrenoceptor reactivity, were not modified by chronic treatment with the antidepressant. However, the contraction mediated by neuronal release of noradrenaline induced by tyramine was increased on days 7 and 21 after denervation in rats treated with fluoxetine. These data indicate that fluoxetine can improve functional recovery after rat vas deferens denervation.

A administração crônica de antidepressivos aumenta os níveis de neurotrofinas no sistema nervoso central, levando a um aumento da arborização neuronal, restabelecendo a rede neural e os níveis de neurotransmissores. Lesões do sistema nervoso periférico mostram uma regeneração muito lenta. Entretanto, a recuperação após a lesão do nervo hipogástrico em roedores é significativamente melhorada após a administração de neurotrofinas. Nesse sentido, nosso objetivo foi verificar se o tratamento com o antidepressivo, fluoxetina, interfere nos níveis de catecolaminas e na função neuronal, após a desnervação cirúrgica do ducto deferente de rato. Nos vasos deferentes desnervados, os níveis de catecolaminas nos grupos tratados com fluoxetina foram maiores que no grupo veículo, quantificados em cromatografia líquida de alta eficiência (CLAE). Nos estudos funcionais, a contração da musculatura lisa induzida pela fenilefrina ou pelo ATP, assim como a reatividade pré-sináptica α2-adrenérgica, não foram modificadas com o tratamento crônico de fluoxetina. Contudo, nas contrações mediadas pela liberação neuronal de norepinefrina induzida por tiramina, observou-se aumento da contração nos dias 7 e 21 após a desnevação em ratos tratados com fluoxetina. Esses dados indicam que a fluoxetina pode melhorar a recuperação funcional do vaso deferente de rato após a desnervação.

Efeito da corrente alternada simétrica sinusoidal na musculatura estriada esquelética desnervada experimentalmente / Effect of sinusoidal alternated current in experimentally denerved skeletal striated muscle

Introdução: A utilização da estimulação elétrica (EE) no tratamento de músculos desnervados tem sido muito estudada, pois auxilia na reinervação tardia e minimiza a atrofia muscular. Objetivo: Neste estudo, avaliamos a EE através da corrente alternada simétrica sinusoidal na manutenção dos aspectos morfológicos dos músculos Extensor longo dos dedos (EDL) e Sóleo desnervados experimentalmente. Método: Quarenta ratos da linhagem wistar foram divididos em quatro grupos experimentais (n=10): Em grupo controle inicial (GCI), controle Final (GCF), desnervado (GD), e em desnervado e estimulado (GDE). A aplicação EE no músculo EDL e sóleo teve início 48 horas após a lesão nervosa, sendo aplicada três vezes por semana durante quarenta e cinco dias. Cortes transversais foram corados com HE para a mensuração da morfometria das fibras musculares. Para a análise estatística foi utilizado a análise de variância (one-way - ANOVA) seguido pelo teste de tukey (p < 0,05). Resultados: Os animais do grupo D e DE apresentaram uma diminuição da área de secção transversal (AST) quando comparadas ao CF. Porém o grupo DE minimizou a atrofia muscular, pois houve diferença estatisticamente significativa quando comparado ao D, tanto no músculo EDL quanto no sóleo. Conclusão: A EE foi eficiente na manutenção dos aspectos morfológicos dos músculos EDL e sóleo, minimizando a atrofia muscular. Podendo ser um tratamento útil para as lesões nervosas periféricas.

Introduction: the use of electrical stimulation (ES) in the treatment of denervated muscles has been studied as it assists in the late reinnervation and minimizes muscle atrophy. Purpose: this study assessed the ES through the symmetric sinusoidal alternating current in the maintenance of the morphological aspects of the experimentally denervated Extensor digitorum longus (EDL) and Soleus muscles. Method: Forty Wister rats were divided into four experimental groups (n = 10): initial control group ( ICG), final control group (FCG), denervated group (DG) and denervated and stimulated group (DSG). ES was first applied in the soleus and EDL muscle 48 hours after nerve injury, the applications took place three times per week for forty-five days. Cross-sections were stained with HE to perform the morphometric analysis of the muscle fibers. We used the analysis of variance (one-way - ANOVA) followed by the Tukey test (p < 0.05) for statistical analysis. Results: the animals belonging to group D and DE showed a decrease in the crosssectional area (CSA) when compared to FCG. However, the group DE had muscular atrophy minimized, as there was a statistically significant difference when compared to D, both for EDL and soleus muscles. Conclusion: the ES was effective in maintaining the morphological aspects of the EDL and soleus muscles, minimizing muscle atrophy. This may be a useful treatment for the peripheral nerve injuries.

Efeito da eletroestimulação no músculo desnervado de animais: revisão sistemática / The effect of electrical stimulation on animals denervated muscle: a systematic review

INTRODUÇÃO: A recuperação funcional após a lesão nervosa periférica está relacionada a fatores intrínsecos e extrínsecos ao sistema nervoso periférico, tais como a gravidade da lesão e a condição dos órgãos-alvo. A atrofia constitui uma das principais alterações do músculo após a lesão nervosa e, uma vez instalada, atua como barreira ao crescimento axonal durante a reinervação muscular. O uso da eletroestimulação é rotineiro no campo da fisioterapia e tem o objetivo de minimizar ou impedir a atrofia muscular e, assim, favorecer a recuperação da lesão nervosa periférica. OBJETIVO: Avaliar os efeitos da eletroestimulação sobre as características tróficas do músculo desnervado. MÉTODOS: Artigos publicados entre 1990 e 2010 e indexados aos bancos de dados da PUBMED foram selecionados utilizando os seguintes descritores: "muscle denervation AND electric stimulation" e "muscular atrophy AND electric stimulation". Foram considerados como critério de inclusão os estudos experimentais em animais (ratos) que utilizassem a lesão nervosa periférica como modelo de desnervação e que avaliassem o efeito da eletroestimulação muscular sobre a área de secção transversa e/ou a massa muscular de músculos desnervados. RESULTADOS: Nove artigos foram selecionados para a revisão. CONCLUSÕES: O efeito da eletroestimulação está diretamente relacionado à característica do protocolo de intervenção, que, quando aplicado de maneira adequada, apresenta o efeito de retardar e, em alguns casos, impedir a atrofia do músculo desnervado.

INTRODUCTION: The functional recovery after peripheral nerve injury is related to extrinsic and intrinsic factors of peripheral nervous system, like trauma severity and conditions of the end-organs. The atrophy is a major change of muscles after nerve injury, and once installed, it acts as a barrier to axonal growth during muscle reinnevation. The use of electrical stimulation is routine in the field of physical therapy and aims to minimize or prevent muscle atrophy and facilitate recovery from peripheral nerve injury. OBJECTIVE: The aim of this review is to evaluate the effects of electrical stimulation on tropics characteristics of denervated muscle. METHODS: Articles published between 1990 and 2010 from periodicals indexed in the PUBMED database were selected, using the following keywords: "muscle denervation AND electric stimulation" and "muscular atrophy AND electric stimulation". Were included experimental studies in animals (rats) that had used a peripheral nerve lesion as a model of muscle denervation and that had evaluated the effect of electrical muscle stimulation on cross-sectional area and/or muscle mass weight of denervated muscles. RESULTS: 9 articles were selected for this review. CONCLUSION: The effect of electrical stimulation is directly related to the intervention protocol's characteristics, which when applied properly had the effect of delaying, in some cases, or prevents the atrophy of denervated muscle.

Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation / Efeitos do laser de baixa potência após reconstrução nervosa na adaptação do músculo sóleo de rato

BACKGROUND: Peripheral nerve injury (PNI) rehabilitation remains a challenge for physical therapists because PNI effects are very disabling. Low-level laser therapy (LLLT) has been described as a physical resource that is able to influence enzymes called metallopeptidases (MMPs) associated with extracellular matrix (ECM) turnover, thus accelerating neuromuscular recovery after nerve crush injuries. However, the effects of LLLT in the treatment of severe nerve injuries and denervated slow-twitch muscles are still inconclusive. OBJECTIVES: The aim of this study was to evaluate the effects of different wavelengths and energy densities of LLLT irradiation, applied to a severe nerve injury after reconstruction, on denervated slow-twitch skeletal muscle adaptation. METHOD: Rats were submitted to a neurotmesis of the sciatic nerve followed by end-to-end neurorrhaphy. They received transcutaneous LLLT irradiation at the lesion site. The LLLT parameters were: wavelengths - 660 or 780 nm; energy densities - 10, 60 or 120 J/cm²; power - 40 mW; spot - 4 mm². Sciatic functional index (SFI), histological, morphometric, and zymographic analyses were performed. One-way ANOVA followed by Tukey's test was used (p<0.05). RESULTS: An atrophic pattern of muscle fibers was observed in all injured groups. The MMP activity in the soleus muscle reached normal levels. On the other hand, SFI remained below normality after PNI, indicating incapacity. No difference was found among PNI groups submitted or not to LLLT in any variable. CONCLUSIONS: LLLT applied to the nerve post-reconstruction was ineffective in delaying degenerative changes to the slow-twitch denervated muscles and in functional recovery in rats. New studies on recovery of denervated slow-twitch muscle are necessary to support clinical practice.

CONTEXTUALIZAÇÃO: A reabilitaçao das lesões nervosas periféricas (LNP) ainda é um desafio para a fisioterapia. A terapia com o laser de baixa potência (LBP) é descrita como um recurso físico capaz de interagir com enzimas relacionadas à alteração da matrix extracelular. Denominadas metalopeptidases (MMPs), essas enzimas atuam durante a recuperação neuromuscular após LNP. No entanto, os efeitos da LBP no tratamento de músculos desnervados de contração lenta após LNP graves ainda são inconclusivos. OBJETIVO: Avaliar os efeitos de diferentes comprimentos de onda e densidades de energia de irradiação de LBP, aplicado sobre o local do nervo após LNP grave e reconstrução. MÉTODO: Ratos foram submetidos a neurotmese do nervo isquiático e neurorrafia término-terminal. Os parâmetros do laser são: comprimento de onda: 660 ou 780 nm; densidades de energia: 10, 60 ou 120 J/cm²; potência: 40 mw; spot: 4 mm². O índice funcional isquiático (IFC) e análises histológicas, morfométricas e zimografia foram realizados. ANOVA one-way e teste de Tukey (p<0,05) foram utilizados. RESULTADOS: Um padrão atrófico das fibras musculares foi observado em todos os grupos com LNP. A atividade das MMPs no músculo sóleo alcançaram níveis normais. Entretanto, o IFC permaneceu inferior à normalidade após a LNP, indicando incapacidade. Não houve diferença entre os grupos de LNP submetidos ou não à LBP em qualquer variável. CONCLUSÃO: O LBP é incapaz de retardar alterações degenerativas em músculos sóleos desnervados e é ineficaz na recuperação funcional de ratos. Novos estudos sobre a recuperação do músculo de contração lenta desnervados são necessários para apoiar a prática clínica.

Ultrastructural transneuronal degeneration study of axonal elements within the paratrigeminal nucleus in sinoaortic deafferented rats / Estudo ultraestrutural de degeneração transneuronal dos elementos axonais do núcleo paratrigeminal de ratos com desnervação sino-aórtica

Objective: Morphological study that searched to authenticate the presence of sinoaortic baroreceptor inputs within the dorsolateral medullary nucleus under electron microscopy analysis. Methods: After a 5-day survival period, 9 baroreceptor-denervated rats deeply anaesthetized with equithesin were transcardially perfused and their brains were histologically processed. Results: The neuronal cytoarchitecture of the paratrigeminal nucleus comprehends afferent projections from other nuclei that have a distributive character regarding visceral and nociceptive functions in the cardiovascular reflex integration response. Conclusion: The medial portion of the nucleus receives afferent projections of the rostral ventrolateral medulla, as shown by retrograde neurotracing studies. The present results show that the medial extent of the paratrigeminal nucleus contains degenerated axoplasmic cellular components in sinoaortic deafferented rats. The number of degenerated axonal fibers was also larger in this area of the nucleus.

Objetivo: Estudo morfológico que buscou verificar, por meio de microscopia eletrônica, a presença de aferências de receptores sino-aórticos em núcleo localizado na região dorso-lateral bulbar. Métodos: Após 5 dias de sobrevida, 9 ratos com desnervação sinoaórtica anestesiados com equitesina foram submetidos à perfusão transcardíaca, e o encéfalo de cada um deles foi processado histologicamente. Resultados: A citoarquitetura neuronal do núcleo paratrigeminal compreende projeções aferentes de outros núcleos que apresentam uma característica distributiva em relação às funções viscerais e nociceptivas na integração do reflexo cardiovascular. Conclusão: A porção medial do núcleo recebe projeções aferentes da região rostro-ventrolateral do troncoencefálico, confirmadas por meio de estudos com rastreadores neuronais. Os resultados indicam que a região medial do núcleo paratrigeminal contém o maior número de fibras axonais degeneradas.

Prevalence of cholelithiasis in patients with chagasic megaesophagus / Prevalência de colelitíase em pacientes com megaesôfago chagásico

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18 percent. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p < 0.0001). The group with chagasic megaesophagus consisted of 59 (43 percent) women and 78 (56.9 percent) men, while the group with idiopathic megaesophagus consisted of 8 (53.3 percent) women and 7 (46.6 percent) men, showing no significant difference between the groups. Of the 137 patients with confirmed chagasic megaesophagus, 39 (28.4 percent) presented cholelithiasis versus one case (6.6 percent) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS: The prevalence of cholelithiasis is high in patients with chagasic megaesophagus and preoperative ultrasound should be performed routinely in these patients in order to treat both conditions during the same surgical procedure.

INTRODUÇÃO: A prevalência de colelitíase observada na população em geral varia de 9 a 18 por cento. Sabe-se que a prevalência de colelitíase é elevada quando existe lesão nervosa parassimpática das vias biliares, causada tanto por procedimentos cirúrgicos (vagotomias),quanto por destruição neuronal, como observado na forma digestiva da doença de Chagas. Propusemo-nos verificar a associação entre megaesôfago de etiologia chagásica e a presença de colelitíase. MÉTODOS: Avaliou-se prospectivamente o exame ultrassonográfico de 152 pacientes portadores de megaesôfago submetidos à cirurgia de cardiomiotomia e esofagectomia subtotal. Analisou-se comparativamente a esofagopatia chagásica e a idiopática com a presença de colelitíase, correlacionando os dados ultrassonográficos com os achados clínicos, idade, sexo e raça. RESULTADOS: Foram analisados 152 casos de megaesôfago, sendo 137 de etiologia chagásica e 15 idiopáticos. Entre os chagásicos, a idade média foi de 56,7 anos (45-67); e nos idiopáticos, a média de idade foi de 35,6 anos (27-44), verificando-se diferença significativa (p < 0,0001) em relação à média de idade. Dos 137 chagásicos, 78 (56,9 por cento) eram do sexo masculino; entre os 15 idiopáticos, 7 (46,6 por cento) eram do sexo masculino. A comparação entre os grupos em relação ao gênero não mostrou diferença significativa. Dentre os 137 chagásicos detectou-se 39 (28,4 por cento) casos de colelitíase e, dentre os 15 casos de megaesôfago idiopático, constatou-se colelitíase em apenas um (6,6 por cento). CONCLUSÕES: Conclui-se que portadores de megaesôfago chagásico possuem alta prevalência de colelitíase, e que a ultrassonografia deve ser realizada rotineiramente no pré-operatório, a fim de tratar ambas as afecções no mesmo ato cirúrgico.

Chronic effect of vagotomy in the morphometry of the myenteric plexus of rats' duodenum / Efeito crônico da vagotomia sobre a morfometria do plexo mioentérico do duodeno de ratos

BACKGROUND: The gastrointestinal disorders have been associated with morphological alterations in the myenteric nervous plexus. AIM: To evaluate, through morphometric studies, the chronic effects of the subdiaphragmatic trunk vagotomy on the nervous plexus. METHODS: Fifteen male exemplars of Wistar Rattus novergicus weighing about 150g, distributed into three groups, have been used: control (n=5), Sham (n=5) and vagotomized (n=5). The animals were sacrificed after 30 and 90 days post surgery. Fragments of duodenum were fixed in Bouin solution, embedded into paraffin and stained with HE and PAS. Morphometric analysis was performed by a Carl Zeiss KM 450 image system. The following aspects were observed: the density of nervous cells per linear micrometer (µm) (ND); the area of perikarya (µm²) (NA); the number of satellite cells per µm (SCD); and the number of satellite cells per neuron (SC/N). The averages were compared with the help of "software" program Sigma Plus through two way - ANOVA and Tuckey post-test. RESULTS: Denervation increased SC/N (p<0,05) and NA (p<0,05), in a time-dependent denervation way (p<0,05). However ND and SCD, decreased, which significantly with the animal's age (p<0,001). CONCLUSION: Vagotomy altered the myenteric plexus morphology in a time-dependent way.

RACIONAL: As disfunções gastrintestinais têm sido associadas à alterações morfológicas no plexo nervoso mioentérico. OBJETIVO: Avaliar através do estudo morfométrico, os efeitos crônicos da vagotomia troncular subdiafragmática sobre esse plexo nervoso. MÉTODOS: Foram utilizados 15 exemplares machos de Rattus novergicus da variedade Wistar, com cerca de 150 g, distribuídos nos grupos controle (n=5), Sham (n=5) e vagotomizados (n=5). Os animais foram sacrificados depois de 30 e 90 dias após as operações. Em seguida, fragmentos do duodeno foram fixados em solução de Bouin, incluídos em parafina e corados por HE e PAS. A análise morfométrica foi realizada por meio do sistema de análise de imagem Carl Zeiss KM 450. Foram observados: a densidade de células nervosas por micrômetro linear (µm); a área dos pericários (µm²); o número de células satélites por µm; e o número de células satélites por neurônio. As médias foram comparadas com o auxílio do programa de "software" Sigma Plus através do Two way - ANOVA e do pós-teste de Tukey. RESULTADOS: A desnervação aumentou o número de células satélites por neurônios (p<0,05) e a área média dos pericários (p<0,05), de maneira dependente do tempo de desnervação (p<0,05), mas diminuiu significativamente a densidade de neurônios (p<0,05) e de células satélites (p<0,05) em função da idade (p<0,001). CONCLUSÃO: A vagotomia alterou a morfologia do plexo mioentérico de maneira dependente do tempo.

Comportamento das reservas de glicogênio no músculo desnervado de ratas tratadas com diferentes doses de estrógeno / Glycogen reserve behavior in denervated muscles of female rats treated with different estrogen doses

OBJETIVO: Avaliar a ação estrogênica sobre o perfil glicogênico do músculo esquelético desnervado de ratas. MÉTODOS: Os animais foram divididos em seis grupos experimentais (n=6): controle; desnervado durante 15 dias; desnervado tratado com estrógeno na concentração de 20µg/peso/dia; desnervado tratado com estrógeno na concentração de 40µg/peso/dia; desnervado tratado com estrógeno na concentração de 80µg/peso/dia e desnervado tratado com estrógeno na concentração de 160µg/peso/dia. Os animais foram tratados com a substância cipionato de estradiol durante 15 dias. As análises realizadas foram: conteúdo de glicogênio dos músculos sóleo, gastrocnêmio branco e gastrocnêmio vermelho (misto), realizadas por meio do método do fenol sulfúrico, além do peso corporal e do músculo sóleo. A análise estatística incluiu ANOVA e teste post-hoc de Tukey (p<0,05). RESULTADOS: A desnervação promoveu redução no conteúdo de glicogênio dos músculos sóleo, gastrocnêmio branco e misto. Por outro lado, nos grupos tratados com estrógeno, foi observada uma elevação progressiva no conteúdo de glicogênio concomitante com a elevação da dose, restabelecendo as reservas glicogênicas, sendo que a concentração mais efetiva foi a de 160µg/peso/dia, em que foram observadas as melhores respostas químio-metabólicas e a menor perda de peso. CONCLUSÃO: Esses resultados sugerem que o estrógeno na concentração de 160µg/peso/dia foi a mais eficiente para minimizar o comprometimento metabólico e pode ser um importante instrumento farmacológico aplicado na prática fisioterapêutica durante a reabilitação.

OBJECTIVE: To evaluate the action of estrogen on the glycogen profile of denervated skeletal muscle in female rats. METHODS: The animals were divided into six experimental groups (n=6): control; denervated for 15 days; denervated and treated with estrogen at a concentration of 20µg/weight/day; denervated and treated with estrogen at a concentration of 40µg/weight/day; denervated and treated with estrogen at a concentration of 80µg/weight/day; and denervated and treated with estrogen at a concentration of 160µg/weight/day. The animals were treated with estradiol cypionate for 15 days. The following analyses were carried out: glycogen content of the soleus, white gastrocnemius and red (mixed) gastrocnemius, by means of the phenol-sulfuric acid method as well as body weight and soleus muscle weight. The statistical analysis included ANOVA and the post-hoc Tukey test (p<0.05). RESULTS: The denervation induced a reduction in glycogen content in the soleus and the white and mixed gastrocnemius muscles. In contrast, there was a progressive elevation of glycogen content concomitant with dose elevation in the groups treated with estrogen, thereby reinstating the glycogen reserves. The most effective concentration was 160µg/weight/day, which showed the best chemometabolic responses and least weight loss. CONCLUSION: These results suggest that estrogen at the concentration of 160 µg/weight/day was the most efficient at minimizing metabolic impairment and that it may be an important pharmacological instrument for physical therapy practice during rehabilitation.

O efeito do intervalo da estimulação elétrica no músculo desnervado de rato / The effect of time interval between electrical stimulation on the denervated rat muscle

OBJETIVO: Comparar o efeito da estimulação elétrica (EE) aplicada diariamente e em dias alternados na densidade de área do tecido conjuntivo (TC) e na área de secção transversa (AST) das fibras do músculo desnervado. MATERIAIS E MÉTODOS: Trinta e cinco ratos foram divididos em grupos controle (C), desnervado (D), desnervado + eletroestimulado diariamente (EED) e desnervado + eletroestimulado em dias alternados (EEA). A aplicação da EE no músculo gastrocnêmio teve início 24 horas após lesão nervosa do tipo axoniotmese, sendo a mesma aplicada durante 20 e 30 dias. Cortes transversais foram corados com HE para mensurações da AST e densidade de área de TC. Análise estatística: teste Shapiro Wilk, seguido pela análise de variância (ANOVA) F (one-way) e teste de Tukey (5 por cento). RESULTADOS: Na análise da densidade de área do TC, observou-se que somente o Grupo EED apresentou valores similares ao Grupo C nos dois períodos analisados. No Grupo 20 dias, não houve diferença na AST quando comparados os grupos submetidos à EE com o Grupo D (p> 0,05), e após 30 dias todos os grupos experimentais alcançaram valores similares ao Grupo C. CONCLUSÕES: A EE não foi eficiente para minimizar a atrofia das fibras musculares. Entretanto, o TC foi responsivo à EE, sendo a aplicação diária mais benéfica ao músculo do que a aplicação em dias alternados, sugerindo que o intervalo de aplicação da EE em músculo desnervado é variável importante para as adaptações do TC.

OBJECTIVE: To compare the effect of electrical stimulation (ES) applied daily and on alternate days, on the area density of the connective tissue (CT) and on the cross-sectional area (CSA) of the denervated muscle fibers. METHODS: Thirty-five rats were divided into the following groups: control (C), denervated (D), denervated + daily electrical stimulation (D+DES) and denervated + alternate-day electrical stimulation (D+ES). The application of ES on the gastrocnemius was started 24 hours after nerve damage of axonotmesis type and was applied for 20 and 30 days. Cross-sections were stained with hematoxylin-eosin to measure the CSA and area density of CT. The statistical analysis consisted of the Shapiro Wilk test followed by analysis of variance (ANOVA) F (one-way) and the Tukey test (p< 0.05). RESULTS: Analysis of the area density of CT showed that only the D+DES Group presented values similar to those of the C Group, for the two analysis periods. There was no difference in CSA in the 20-day Group between the ES Groups and the D Group (p> 0.05). After 30 days, all the experimental groups reached CSA values similar to the C Group. CONCLUSIONS: The ES was inefficient for minimizing the muscle fiber atrophy. However, the CT was responsive to ES, and daily applications were more beneficial for the muscle than were alternate-day applications, thus suggesting that the interval for applying ES to denervated muscle is an important variable for CT adaptation.