RESUMO
BACKGROUND AND AIM: Although it is well established that hormones like glucagon stimulates gluconeogenesis via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2, the role of neural signals in the regulation of gluconeogenesis remains uncertain. METHODS AND RESULTS: Here, we characterize the noradrenergic bundle architecture in mouse liver; we show that the sympathoexcitation induced by acute cold exposure promotes hyperglycemia and upregulation of gluconeogenesis via triggering of the CREB/CRTC2 pathway. Following its induction by dephosphorylation, CRTC2 translocates to the nucleus and drives the transcription of key gluconeogenic genes. Rodents submitted to different models of sympathectomy or knockout of CRTC2 do not activate gluconeogenesis in response to cold. Norepinephrine directly acts in hepatocytes mainly through a Ca2+-dependent pathway that stimulates CREB/CRTC2, leading to activation of the gluconeogenic program. CONCLUSION: Our data demonstrate the importance of the CREB/CRTC2 pathway in mediating effects of hepatic sympathetic inputs on glucose homeostasis, providing new insights into the role of norepinephrine in health and disease.
Assuntos
Temperatura Baixa , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Gluconeogênese , Fígado , Norepinefrina , Fatores de Transcrição , Animais , Gluconeogênese/fisiologia , Fígado/metabolismo , Camundongos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Masculino , Norepinefrina/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Neurônios Adrenérgicos/metabolismo , Neurônios Adrenérgicos/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/fisiologia , Hepatócitos/metabolismoRESUMO
Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.
Assuntos
Clembuterol , Modelos Animais de Doenças , Fibromialgia , Hiperalgesia , Atrofia Muscular , Sistema Nervoso Simpático , Animais , Feminino , Fibromialgia/patologia , Fibromialgia/fisiopatologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Hiperalgesia/fisiopatologia , Hiperalgesia/patologia , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/patologia , Clembuterol/farmacologia , Ratos , Carragenina/toxicidade , Ratos Sprague-Dawley , Dor/patologia , Dor/fisiopatologia , Epinefrina , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Catecolaminas/metabolismo , Agonistas Adrenérgicos beta/farmacologiaRESUMO
BACKGROUND: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. SUMMARY: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease. KEY MESSAGES: During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.
Assuntos
Encéfalo , Doença de Chagas , Timo , Humanos , Doença de Chagas/imunologia , Doença de Chagas/fisiopatologia , Animais , Encéfalo/imunologia , Timo/imunologia , Timo/fisiologia , Trypanosoma cruzi/fisiologia , Trypanosoma cruzi/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Neuroimunomodulação/fisiologia , Neuroimunomodulação/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Since their discovery in 2000, there has been a continuous expansion of studies investigating the physiology, biochemistry, and pharmacology of endocrine fibroblast growth factors (FGFs). FGF19, FGF21, and FGF23 comprise a subfamily with attributes that distinguish them from typical FGFs, as they can act as hormones and are, therefore, referred to as endocrine FGFs. As they participate in a broad cross-organ endocrine signaling axis, endocrine FGFs are crucial lipidic, glycemic, and energetic metabolism regulators during energy availability fluctuations. They function as powerful metabolic signals in physiological responses induced by metabolic diseases, like type 2 diabetes and obesity. Pharmacologically, FGF19 and FGF21 cause body weight loss and ameliorate glucose homeostasis and energy expenditure in rodents and humans. In contrast, FGF23 expression in mice and humans has been linked with insulin resistance and obesity. Here, we discuss emerging concepts in endocrine FGF signaling in the brain and critically assess their putative role as therapeutic targets for treating metabolic disorders.
Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Humanos , Animais , Camundongos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Homeostase , Encéfalo/metabolismo , Obesidade/tratamento farmacológicoRESUMO
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.
Assuntos
Leptina , Norepinefrina , Feminino , Tecido Adiposo/metabolismo , Dieta , Leptina/metabolismo , Norepinefrina/metabolismo , Obesidade/metabolismo , Sistema Nervoso Simpático , Animais , RatosRESUMO
Background: Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods: A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results: Both interventions increased circulating SIRT1 (p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men (p = 0.045), but not in women. SIRT1 was an independent predictor of NMD (p = 0.026) only in the energy restriction group. Conclusions: Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group.
Assuntos
Sirtuína 1 , Estilbenos , Masculino , Adulto , Humanos , Feminino , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Glucose/metabolismo , Lipídeos , Insulina , Estilbenos/farmacologiaRESUMO
BACKGROUND: Differential diagnosis is a hot topic in physical therapy, especially for those working in a direct access setting dealing with neck pain and its associated disorders. All international guidelines agree in recommending to first rule out non-musculoskeletal pathologies as the cause of signs and symptoms in the patient. Although the autonomic nervous system (ANS) has a crucial role and is also involved in pain conditions, coverage of it in neuroscience textbooks and educational programmes is limited and most healthcare professionals are unfamiliar with it. Although autonomic conditions are benign in nature, they are clinically of great importance as they may be a 'red flag' warning of an injury along the sympathetic pathway. Therefore, sound knowledge of the ANS system is essential for clinicians. OBJECTIVE: To develop physical therapists' knowledge of and confidence in understanding cervical ANS function and dysfunction, thus enhancing clinical reasoning skills and the pattern recognition process, and performing and interpreting objective examinations. METHODS: This master class provides an introductory guide and essential knowledge to facilitate clinicians to understand cervical autonomic dysfunctions and their clinical evaluation. The optimal referral method is also handled. CONCLUSIONS: Gaining knowledge and understanding of the ANS, its function, its dysfunction, and the related clinical manifestations is likely to lead to a decision-making process driven by 'science and conscience'. This will empower physical therapists to be aware of subtle clues that may be offered by patients during the interview and history intake leading to the appropriate physical examination and triage.
Assuntos
Sistema Nervoso Autônomo , Doenças Musculoesqueléticas , Humanos , Exame Físico , Cervicalgia , Modalidades de FisioterapiaRESUMO
Cardiac innervation by the parasympathetic nervous system (PNS) and the sympathetic nervous system (SNS) modulates the heart rate (HR) (chronotropic activity) and the contraction of the cardiac muscle (inotropic activity). The peripheral vasculature is controlled only by the SNS, which is responsible for peripheral vascular resistance. This also mediates the baroreceptor reflex (BR), which in turn mediates blood pressure (BP). Hypertension (HTN) and the autonomic nervous system (ANS) are closely related, such that derangements can lead to vasomotor impairments and several comorbidities, including obesity, hypertension, resistant hypertension, and chronic kidney disease. Autonomic dysfunction is also associated with functional and structural changes in target organs (heart, brain, kidneys, and blood vessels), increasing cardiovascular risk. Heart rate variability (HRV) is a method of assessing cardiac autonomic modulation. This tool has been used for clinical evaluation and to address the effect of therapeutic interventions. The present review aims (a) to approach the heart rate (HR) as a CV risk factor in hypertensive patients; (b) to analyze the heart rate variability (HRV) as a "tool" to estimate the individual risk stratum for Pre-HTN (P-HTN), Controlled-HTN (C-HTN), Resistant and Refractory HTN (R-HTN and Rf-HTN, respectively), and hypertensive patients with chronic renal disease (HTN+CKD).
RESUMO
BACKGROUND: Salt-sensitive hypertension in humans and experimental models is associated with higher plasma and cerebrospinal fluid sodium chloride (NaCl) concentrations. Changes in extracellular NaCl concentrations are sensed by specialized neurons in the organum vasculosum of the lamina terminalis (OVLT). Stimulation of OVLT neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP), whereas chronic activation produces hypertension. Therefore, the present study tested whether OVLT neuronal activity was elevated and contributed to SNA and ABP in salt-sensitive hypertension. METHODS: Male Dahl salt-sensitive (Dahl S) and Dahl salt-resistant (Dahl R) rats were fed 0.1% or 4.0% NaCl diets for 3 to 4 weeks and used for single-unit recordings of OVLT neurons or simultaneous recording of multiple sympathetic nerves during pharmacological inhibition of the OVLT. RESULTS: Plasma and cerebrospinal fluid Na+ and Cl- concentrations were higher in Dahl S rats fed 4% versus 0.1% or Dahl R rats fed either diet. In vivo single-unit recordings revealed a significantly higher discharge of NaCl-responsive OVLT neurons in Dahl S rats fed 4% versus 0.1% or Dahl R rats. Interestingly, intracarotid infusion of hypertonic NaCl evoked greater increases in OVLT neuronal discharge of Dahl S versus Dahl R rats regardless of NaCl diet. The activity of non-NaCl-responsive OVLT neurons was not different across strain or diets. Finally, inhibition of OVLT neurons by local injection of the gamma-aminobutyric acid agonist muscimol produced a greater decrease in renal SNA, splanchnic SNA, and ABP of Dahl S rats fed 4% versus 0.1% or Dahl R rats. CONCLUSIONS: A high salt diet activates NaCl-responsive OVLT neurons to increase SNA and ABP in salt-sensitive hypertension.
Assuntos
Hipertensão , Organum Vasculosum , Ratos , Animais , Humanos , Masculino , Cloreto de Sódio/farmacologia , Ratos Sprague-Dawley , Alta do Paciente , Ratos Endogâmicos Dahl , Cloreto de Sódio na Dieta , Hipotálamo , Pressão Sanguínea/fisiologiaRESUMO
Diabetes mellitus (DM) is a metabolic disorder whose prevalence has continuously increased worldwide and is associated with dysfunction of the autonomic nervous system and, in particular, that of the sympathetic nervous system (SNS). The objective of this study was to analyze the interaction of DM and the SNS, building a model of sympathectomized diabetic rats to determine alterations in the content of CA (catecholamines) in different intra-abdominal organs. Sympathectomy was conducted with guanethidine (GNT). Additionally, DM was induced with STZ (Streptozotocin). Treatment with GNT decreased norepinephrine (NE) content in all analyzed tissues, with significant differences found in the paraganglia, liver, pancreas, duodenum, and heart compared to the control group. With respect to epinephrine (E), which was only found in the liver, pancreas, and heart, presenting significant differences (p < 0.05) in the heart, a decrease in its concentration was observed for all of the experimental groups with respect to the control. The decrease in dopamine (DA) content due to the GNT−STZ treatment was 30.1% in the heart with respect to the diabetic (STZ) group. The amount of CA in the adrenal medulla indicates the effect of sympathectomy on the GNT group where there was a significant reduction (p < 0.05) of DA. These findings suggest that the elimination of the sympathetic nervous system in diabetic organisms contributed to a decrease in blood glucose; likewise, an alteration in the levels of CA was observed in the different selected organs, possibly attributed to the severity, duration, and pathogenesis of the complications of acute and chronic DM.
RESUMO
Abstract Background Sudden cardiac death is the main lethal mechanism associated with Chagas cardiomyopathy. Studies suggest that dysautonomia may represent a relevant, intense, independent, and early phenomenon in the natural history of the disease, even when ventricular systolic function is preserved, and may also be the mechanism that triggers malignant ventricular arrhythmias. Objective To evaluate the degree of dysautonomia and its possible association with ventricular arrhythmias in patients with Chagas cardiomyopathy, according to different categories of mortality risk, as defined by the score proposed by Rassi, used as a surrogate outcome for death. Methods A cross-sectional study involving 43 patients with Chagas cardiomyopathy stratified into risk categories based on the Rassi score, with 23 being classified as low risk and 20 as intermediate-to-high risk. Heart rate variability (HRV) was assessed using Holter monitoring for long-term recordings of 24 hours (time domain) and for short-term recordings of 5 minutes (frequency domain) at rest and after autonomic tests: deep breathing and Valsalva maneuver. The HRV variables were compared between the groups using the Student's t-test and α=0.05. Results Comparison of the results between the risk stratification groups showed no differences in HRV indexes, either in the time or frequency domain. However, results showed a significant increase in the number of arrhythmias as a function of increased risk (p=0.02). Conclusion There was no association between the degree of dysautonomia, evaluated by Holter monitoring, and the categories of mortality risk, despite a direct association between the rate of arrhythmias and the higher risk group.
RESUMO
The idea that the nervous system communicates with the immune system to regulate physiological and pathological processes is not new. However, there is still much to learn about how these interactions occur under different conditions. The carotid body (CB) is a sensory organ located in the neck, classically known as the primary sensor of the oxygen (O2) levels in the organism of mammals. When the partial pressure of O2 in the arterial blood falls, the CB alerts the brain which coordinates cardiorespiratory responses to ensure adequate O2 supply to all tissues and organs in the body. A growing body of evidence, however, has demonstrated that the CB is much more than an O2 sensor. Actually, the CB is a multimodal sensor with the extraordinary ability to detect a wide diversity of circulating molecules in the arterial blood, including inflammatory mediators. In this review, we introduce the literature supporting the role of the CB as a critical component of neuroimmune interactions. Based on ours and other studies, we propose a novel neuroimmune pathway in which the CB acts as a sensor of circulating inflammatory mediators and, in conditions of systemic inflammation, recruits a sympathetic-mediated counteracting mechanism that appears to be a protective response.
Assuntos
Corpo Carotídeo , Animais , Neuroimunomodulação , Oxigênio/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Mamíferos/metabolismoRESUMO
Macrophages are immune cells that are widespread throughout the body and critical for maintaining tissue homeostasis. Their remarkable plasticity allows them to acquire different phenotypes, becoming able either to fight infection (M1-like, classically activated macrophages) or to promote tissue remodeling and repair (M2-like, alternatively activated macrophages). These phenotypes are induced by different cues present in the microenvironment. Among the factors that might regulate macrophage activation are mediators produced by different branches of the nervous system. The regulation exerted by the sympathetic nervous system (SNS) on macrophages (and the immune system in general) is becoming a subject of increasing interest, indeed a great number of articles have been published lately. Catecholamines (noradrenaline and adrenaline) activate α and ß adrenergic receptors expressed by macrophages and shape the effector functions of these cells in contexts as diverse as the small intestine, the lung, or the adipose tissue. Activation of different subsets of receptors seems to produce antagonistic effects, with α adrenergic receptors generally associated with pro-inflammatory functions and ß adrenergic receptors (particularly ß2) related to the resolution of inflammation and tissue remodeling. However, exceptions to this paradigm have been reported, and the factors contributing to these apparently contradictory observations are still far from being completely understood. Additionally, macrophages per se seem to be sources of catecholamines, which is also a subject of some debate. In this review, we discuss how activation of adrenergic receptors modulates macrophage effector functions and its implications for inflammatory responses and tissue homeostasis.
RESUMO
SUMMARY OBJECTIVE: This study aims to compare heart rate variability (HRV) between patients with chronic neck pain and patients with chronic low back pain and to correlate the chronic pain variables with heart rate variability indices. METHODS: This is a cross-sectional study. We divided the sample into two groups: neck pain (n=30) and low back pain (n=30). We used the Numeric Pain Rating Scale, Neck Disability Index, Roland-Morris Disability Questionnaire, Pain-Related Catastrophizing Thoughts Scale, Tampa Scale of Kinesiophobia, and Pain Self-Efficacy Questionnaire. For heart rate variability analysis, we used the following indices: mean RR, standard deviation of all RR intervals, mean heart rate, root mean square differences of successive RR intervals, triangular index, triangular interpolation of the interval histogram, low-frequency band in arbitrary units and in absolute values, high-frequency band in arbitrary units and in absolute values, standard deviation of the instantaneous beat-to-beat variability (standard deviation 1), long-term standard deviation of continuous RR intervals (standard deviation 2), and Stress Index. We used Student's t-test for comparisons and Spearman's coefficient for correlations. RESULTS: We observe insignificant values in the differences between the groups. Disability and self-efficacy were correlated with heart rate variability only in patients with chronic neck pain, whereas catastrophizing and kinesiophobia showed greater correlations with heart rate variability in patients with chronic low back pain. CONCLUSIONS: Autonomic dysfunction of individuals with chronic neck pain, when compared to patients with chronic low back pain, does present insignificant differences.
RESUMO
INTRODUCTION: Pulmonary artery denervation (PADN) can reduce the sympathetic nervous system (SNS) activity, reduce pulmonary artery pressure (PAP), and improve the quality of life in patients with pulmonary hypertension (PH). We conducted a systematic meta-analysis of the effectiveness of PADN in the treatment of PH patients. METHODS: This is a comprehensive literature search including all public clinical trials investigating the effects of PADN on PH. Outcomes were mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), right ventricular (RV) Tei index, 6-minute walk distance (6MWD), and New York Heart Association (NYHA) cardiac function grading. RESULTS: A total of eight clinical studies with 213 PH patients who underwent PADN were included. Meta-analysis showed that after PADN, mPAP (mean difference [] -12.51, 95% confidence interval [CI] -17.74 to -7.27, P<0.00001) (mmHg) and PVR ( -5.17, 95% CI -7.70 to -2.65, P<0.0001) (Wood unit) decreased significantly, CO ( 0.59, 95% CI 0.32 to 0.86, P<0.0001) (L/min) and 6MWD ( 107.75, 95% CI 65.64 to 149.86, P<0.00001) (meter) increased significantly, and RV Tei index ( -0.05, 95% CI -0.28 to 0.17, P=0.63) did not change significantly. Also after PADN, the proportion of NYHA cardiac function grading (risk ratio 0.23, 95% CI 0.14 to 0.37, P<0.00001) III and IV decreased significantly. CONCLUSION: This meta-analysis supports PADN as a potential new treatment for PH. Further high-quality randomized controlled studies are needed.
Assuntos
Hipertensão Pulmonar , Artéria Pulmonar , Denervação , Humanos , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar/cirurgia , Qualidade de Vida , Resistência VascularRESUMO
ABSTRACT Introduction: Pulmonary artery denervation (PADN) can reduce the sympathetic nervous system (SNS) activity, reduce pulmonary artery pressure (PAP), and improve the quality of life in patients with pulmonary hypertension (PH). We conducted a systematic meta-analysis of the effectiveness of PADN in the treatment of PH patients. Methods: This is a comprehensive literature search including all public clinical trials investigating the effects of PADN on PH. Outcomes were mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), right ventricular (RV) Tei index, 6-minute walk distance (6MWD), and New York Heart Association (NYHA) cardiac function grading. Results: A total of eight clinical studies with 213 PH patients who underwent PADN were included. Meta-analysis showed that after PADN, mPAP (mean difference [MD] -12.51, 95% confidence interval [CI] -17.74 to -7.27, P<0.00001) (mmHg) and PVR (MD -5.17, 95% CI -7.70 to -2.65, P<0.0001) (Wood unit) decreased significantly, CO (MD 0.59, 95% CI 0.32 to 0.86, P<0.0001) (L/min) and 6MWD (MD 107.75, 95% CI 65.64 to 149.86, P<0.00001) (meter) increased significantly, and RV Tei index (MD -0.05, 95% CI -0.28 to 0.17, P=0.63) did not change significantly. Also after PADN, the proportion of NYHA cardiac function grading (risk ratio 0.23, 95% CI 0.14 to 0.37, P<0.00001) III and IV decreased significantly. Conclusion: This meta-analysis supports PADN as a potential new treatment for PH. Further high-quality randomized controlled studies are needed.
RESUMO
The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.
Assuntos
Sistema Cardiovascular , Reflexo , Animais , Pressão Sanguínea/fisiologia , Exercício Físico/fisiologia , Humanos , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Reflexo/fisiologiaRESUMO
INTRODUCTION: Patients with pancreatic cancer, chronic pancreatitis and other abdominal pain syndromes may develop debilitating pain throughout the course of their illness with little to no relief by most conventional methods. While some form of relief is experienced by patients, not all benefit from these procedures and side effects, while transitory in most cases are severe and often not expected. Our aim was therefore to investigate the anatomy surrounding the abdominal sympathetic ganglia, the target for the invasive procedures in an attempt to understand the variations in results. MATERIALS AND METHODS: The abdominal cavities of nine individuals were dissected and the ganglia investigated, harvested and histologically and immunochemical stained. RESULTS: The phrenic ganglion was found inconsistently and more often in the left than the right. If present it was located in association with the inferior phrenic artery and often connected to the celiac ganglion. The celiac ganglion was located anterior to the diaphragmatic crus on both sides and specifically posteromedial to the suprarenal gland and superior to the renal artery on the left. On the right it was located posterior to the suprarenal gland and inferior vena cava also superior to the renal vessels. The superior mesenteric ganglion was only positively identified in one individual and was located on the left lateral aspect of the superior mesenteric artery. CONCLUSION: The blockade procedures for treatment of pain are developed to target the area around the celiac artery where the ganglion is commonly described to be located. However, based on our results of its location and interconnections the ganglion is not located in the targeted area.
Assuntos
Plexo Celíaco , Gânglios Simpáticos , Abdome , Plexo Celíaco/anatomia & histologia , Gânglios Simpáticos/anatomia & histologia , Humanos , Dor , Artéria RenalRESUMO
Avaliar os efeitos de diferentes frequências moduladas em amplitude (AMF-100Hz e AMF-10Hz) da corrente interferencial (CI) sobre o sistema nervoso autônomo (SNA) de voluntários saudáveis. Trinta voluntários saudáveis (23,7±2,7 anos) foram randomizados em intervenções placebo (desligado), CI com AMF-100Hz e CI com AMF-10Hz. As intervenções foram aplicadas na região ganglionar paravertebral por 30 minutos. O SNA foi avaliado pela variabilidade da frequência cardíaca antes e imediatamente após as intervenções. A intervenção em 10Hz reduziu a atividade simpática em 6% e aumentou a parassimpática em 6%. A intervenção de 100Hz aumentou 12% para a atividade simpática e diminuiu 12% para a atividade parassimpática. A CI altera o equilíbrio autonômico em voluntários saudáveis. 10Hz reduz a atividade simpática e aumenta parassimpático, embora o 100Hz tenha resultados opostos. A CI a 10Hz melhora o equilíbrio autonômico e apresenta efeitos potenciais a serem testados em pacientes hipertensos.
To evaluate the effects of different amplitude-modulated frequency (AMF-100Hz and AMF-10Hz) of the interferential current (IC) on autonomic nervous system (ANS) in healthy volunteers. Thirty healthy volunteers (23.7 ±2.7 years old) were randomized into placebo interventions (turned off), IC with AMF-100Hz and IC with AMF-10Hz. Interventions ware applied in the paravertebral ganglionar region for 30 minutes. ANS evaluated by the heart rate variability before and immediately after the interventions. 10Hz intervention reduced the sympathetic activity in 6% and an increase in the parasympathetic in 6%. 100Hz intervention increased 12% to sympathetic activity and decreased 12% to parasympathetic activity. IC changes the autonomic balance in healthy volunteers. 10Hz reduces the sympathetic activity and increases parasympathetic, although the 100Hz has opposite results. The IC at 10Hz improves the autonomic balance and presents potential effects to be tested in hypertensive patients.
RESUMO
Obesity is a chronic condition of multifactorial etiology characterized by excessive body fat due to a calorie intake higher than energy expenditure. Given the intrinsic limitations of surgical interventions and the difficulties associated with lifestyle changes, pharmacological manipulation is currently one of the main therapies for metabolic diseases. Approaches aiming to promote energy expenditure through induction of thermogenesis have been explored and, in this context, brown adipose tissue (BAT) activation and browning have been shown to be promising strategies. Although such processes are physiologically stimulated by the sympathetic nervous system, not all situations that are known to increase adrenergic signaling promote a concomitant increase in BAT activation or browning in humans. Thus, a better understanding of factors involved in the thermogenesis attributed to these tissues is needed to enable the development of future therapies against obesity. Herein we carry out a critical review of original articles in humans under conditions previously known to trigger adrenergic responses-namely, cold, catecholamine-secreting tumor (pheochromocytoma and paraganglioma), burn injury, and adrenergic agonists-and discuss which of them are associated with increased BAT activation and browning. BAT is clearly stimulated in individuals exposed to cold or treated with high doses of the ß3-adrenergic agonist mirabegron, whereas browning is certainly induced in patients after burn injury or with pheochromocytoma, as well as in individuals treated with ß3-adrenergic agonist mirabegron for at least 10 weeks. Given the potential effect of increasing energy expenditure, adrenergic stimuli are promising strategies in the treatment of metabolic diseases.