RESUMEN

SUMMARY OBJECTIVE: The aim of this study was to demonstrate the effect of coronavirus disease 2019 on the cardiovascular autonomic system using heart rate variability in young individuals. METHODS: The study was designed retrospectively by scanning the 24-h Holter electrocardiography records of patients who applied to the Ankara Abdurrahman Yurtaslan Oncology Education and Research Hospital Cardiology outpatient clinic. The study group consisted of 492 patients under the age of 40 years, who did not have additional comorbidities or medication use and had prolonged symptoms after coronavirus disease 2019 during the pandemic. The control group, including 401 patients, was determined during the pre-pandemic period (before December 2019). Heart rate variability parameters were evaluated by scanning the 24-h Holter electrocardiography records of the patients and compared with the non-coronavirus disease 2019 group. RESULTS: The median age of participants was 30 years. Standard deviation of normal RR intervals (SDNN) ≤100 ms was more prevalent in the study group (27 (6.7%) vs 73 (14.8%), p<0.001). In univariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.41, 95%CI 1.52-3.83), p<0.001] and age [(OR 1.04, 95%CI 1.01-1.07), p=0.016] had a significant effect on the probability of SDNN≤100. In multivariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.42, 95%CI 1.52-3.85), p<0.001] and age [(OR 2.42, 95%CI 1.52-3.85), p=0.016] had a significant effect on the probability of SDNN≤100. Frequency domain measures such as, high-frequency values were significantly higher in the study group (p=0.029). The study group's low-frequency/high frequency ratio was significantly lower (p=0.019). The low-frequency/high-frequency ratio's cut-off value was ≤2.77. for determining the differentiation between coronavirus disease 2019 positive and negative cases in the receiver operating characteristic analysis. The sensitivity rate was 80.7%. The area under the curve value is 0.546 (p=0.019). CONCLUSION: This study showed that coronavirus disease 2019 causes reduced heart rate variability and increased parasympathetic activity in young patients. This may explain the prolonged symptoms after coronavirus disease 2019 infection.

RESUMEN

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Asunto(s)

RESUMEN

PURPOSE: To carry out a systematic review to determine the main methods used to study the heart rate variability (HRV) in individuals after the acute phase of COVID-19. METHODS: The study followed the Preferred Items for Reporting for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Web of Science, Scopus and CINAHAL electronic databases were searched from the inception to November 2022. The studies were included if they used HRV assessment based on linear and non-linear methods in long-term COVID-19 patients. Review studies, theses and dissertations, conference abstracts, longitudinal studies, studies conducted on animals and studies that included individuals in the acute phase of the COVID-19 were excluded. The methodological quality of the studies was analyzed using the Joanna Briggs Institute's critical evaluation checklist for cross-sectional analytical studies. RESULTS: HRV was mainly assessed using 24-h Holter monitoring in 41.6% (5/12) of the studies, and 12­lead ECG was used in 33.3% (4/12). Regarding the type of assessment, 66.6% (8/12) of the studies only used linear analysis, where 25% (3/12) used analysis in the time domain, and 41.6% (5/12) used both types. Non-linear methods were combined with the previously cited linear method in 25% (3/12) of the studies. Moreover, 50% (6/12) of the studies demonstrated post-COVID-19 autonomic dysfunction, with an increase in the predominance of cardiac sympathetic modulation. The average score of the evaluation checklist was 6.6, characterized as having reasonable methodological quality. CONCLUSION: 24-h Holter and 12­lead ECG are considered effective tools to assess HRV in post-COVID-19 patients. Furthermore, the findings reveal diverse effects of COVID-19 on the autonomic nervous system's sympathovagal balance, which might be influenced by secondary factors such as disease severity, patients' overall health, evaluation timing, post-infection complications, ventilatory functions, and age.

Asunto(s)

RESUMEN

ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

RESUMEN

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).

RESUMEN

BACKGROUND: Almost a third of patients with Guillain-Barré Syndrome (GBS) require mechanical ventilation, increasing mortality by 15-30% and proving poor functional outcomes. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is the most frequently used scale to assess probability of respiratory insufficiency within the first week of admission. We aim to determine other clinical and electrophysiological prognostic factors for invasive mechanical ventilation (IMV) in patients with GBS. MATERIAL AND METHODS: A cross-sectional ambispective cohort study was carried out in a referral center in Mexico City, from January 2015 to December 2019. Baseline demographics, MRC score, Hughes scale, EGRIS, dysautonomia and nerve conduction studies were performed on admission in GBS patients that required IMV. A multivariable analysis for IMV and a survival analysis for independent walk in prolonged-IMV (>14 days) were performed. RESULTS: Forty-nine (32%) out of 153 GBS patients required IMV. Statistically significant prognostic factors in multivariable analysis were deltoid muscle strength ≤2 [OR 7.1 (1.6-31.1)], EGRIS [OR 2.5 (1.3-4.6)] and autonomic dysfunction [OR 6.6 (2.0-22.0)]. Electrodecrement <1 mV in the compound muscle action potential (CMAP) of distal motor median nerve was more prevalent in prolonged-IMV patients (44.8% vs. 21%, p = .049). A significant minor prevalence of prolonged-IMV patients regain independent walk at 6 months using the Kaplan-Meier method (log rank test p < .001). CONCLUSIONS: We provide new specific clinical (deltoid muscle strength and autonomic dysfunction) and electrophysiological variables to discriminate GBS patients that will require IMV.

Asunto(s)

RESUMEN

Autonomic dysfunction related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is increasingly described in the literature. We report the case of a 30-year-old male with a background of asthma and migraine who experienced a second episode of SARS-CoV-2 infection characterized by mild respiratory symptoms. Twenty-four days after the symptom onset, he developed acute syncope. A tilt test revealed a neuromediated cardioinhibitory response with asystole (Vasovagal Syncope International Study ­ VASIS type 2B). The temporal association between SARS-CoV-2 infection and syncope seems to indicate a probable causal relationship, which requires corroboration by future studies.

Disfunção autonômica relacionada à infecção por coronavírus-2 da síndrome respiratória aguda grave (SARS-CoV-2) vem sendo cada vez mais descrita na literatura. Relatamos o caso de um homem de 30 anos de idade, com histórico de asma e enxaqueca, que apresentou um segundo episódio de infecção por SARS-CoV-2 caracterizado por sintomas respiratórios leves. Vinte e quatro dias após o início dos sintomas, desenvolveu um quadro agudo de síncope. Um teste de inclinação revelou uma resposta cardioinibitória neuromediada com assistolia (Vasovagal Syncope International Study ­ VASIS tipo 2B). A associação temporal entre infecção por SARS-CoV-2 e síncope parece indicar uma provável relação causal, a qual requer corroboração por estudos futuros.

RESUMEN

ABSTRACT BACKGROUND: Coronary artery disease is an important cause of morbidity and mortality. The impact of ventricular arrhythmias with impaired cardiac vagal activity is one of the most recently studied prognostic factors. However, there are no studies evaluating the phenomenon of heart rate turbulence (HRT) during physical exertion. OBJECTIVE: To study the behavior of HRT during exercise testing, among individuals after myocardial infarction. DESIGN AND SETTING: Feasibility study conducted in a university hospital among individuals 4-6 weeks after myocardial infarction. METHODS: All subjects underwent 24-hour Holter monitoring and ergometric stress testing. We considered that abnormal HRT was present if the turbulence onset was ≥ 0% or turbulence slope was ≤ 2.5 mm/relative risk interval. RESULTS: All 32 subjects were asymptomatic. Their median age was 58 years (interquartile range 12.8) and 70% were male. Abnormal HRT was associated with ventricular dysfunction in this population. We found no differences regarding the behavior of HRT, in relation to age, gender, smoking, systemic arterial hypertension, diabetes mellitus or dyslipidemia. Ergometric stress testing detected premature ventricular beats (PVB) in approximately 44% of the examinations, and these occurred both during the active phase of effort and in the recovery period. The low occurrence of several isolated PVB in beta-blocked subjects made it difficult to perform statistical analysis to correlate HRT between ergometric and Holter testing. CONCLUSION: The data obtained in this study do not support performing HRT through ergometric stress testing among patients who remain on beta-blockers post-myocardial infarction, for the purpose of assessing cardiac vagal activity.

RESUMEN

The aim of this study was to compare the physical fitness and cardiac autonomic activity among women with moderate and severe fibromyalgia (FM) and healthy women. This study included 35 women with FM (age: 46.2±8.9 years) and 17 healthy women (age: 44.3±9.9 years). Participants with FM were divided into moderate FM (n=15) and severe FM (n=20) according to the total score obtained in FM impact questionnaire. The heart rate variability was monitored using a portable cardiac monitor with participants resting in supine position during 10 min. Thereafter, the participants performed the chair sit and reach test, the chair stand test, and the 6-min walk test to measure the lower-body flexibility, lower-body muscle strength, and cardiorespiratory fitness, respectively. The lower-body muscle strength and cardiorespiratory fitness were both reduced in moderate and severe FM compared to healthy women (P<0.01), with greater reduction in severe FM when compared to moderate FM (P<0.05). In addition, the parasympathetic indexes of heart rate variability were all similarly decreased in both moderate and severe FM, when compared to healthy women (P<0.05). The cardiac parasympathetic activity is similarly decreased in women with both moderate and severe FM in comparison to healthy women, despite a greater physical deconditioning in severe FM.

RESUMEN

BACKGROUND: Guillain-Barré syndrome is the most common cause of flaccid paralysis, with multiple known clinical variants. Autonomic dysfunction, although frequently reported in the clinical course, is often overlooked in the pediatric population and is usually not the initial presenting symptom in this age group CASE PRESENTATION: We present the case of a previously healthy 17-year-old who arrived at the Emergency Department complaining of gastrointestinal symptoms associated with lipothymia. An initial electrocardiogram (ECG) showed sustained sinus bradycardia subsequently associated with arterial hypertension. Structural and inflammatory cardiac pathology were ruled out, as well as auriculoventricular conduction block and posterior reversible encephalopathy syndrome. On the ninth day after initial symptoms, the patient presented sensory and motor nerve disturbances with the cerebrospinal fluid analysis showing a clear albumin-cytologic dissociation, consistent with an atypical presentation of GBS with autonomic dysfunction. Immunoglobulin therapy was administered, developing subsequent aseptic meningitis, that required discontinuation of previous therapy and treatment with plasmapheresis. Clinical improvement was achieved with full motor function recovery. CONCLUSION: This case illustrates a Guillain-Barré syndrome variant in which autonomic dysfunction preceded neurologic deficit, a finding uncommon in children, emphasizing this as an important differential diagnosis for severe bradycardia in pediatric patients.

Asunto(s)

RESUMEN

ABSTRACT BACKGROUND: Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. OBJECTIVE: To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. DESIGN AND SETTING: Prospective observational study conducted in the Federal University of São Paulo. METHOD: A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. RESULTS: The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. High-risk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. CONCLUSION: Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.

Asunto(s)

RESUMEN

A significant percentage of COVID-19 survivors develop long-lasting cardiovascular sequelae linked to autonomic nervous system dysfunction, including fatigue, arrhythmias, and hypertension. This post-COVID-19 cardiovascular syndrome is one facet of "long-COVID," generally defined as long-term health problems persisting/appearing after the typical recovery period of COVID-19. Despite the fact that this syndrome is not fully understood, it is urgent to develop strategies for diagnosing/managing long-COVID due to the immense potential for future disease burden. New diagnostic/therapeutic tools should provide health personnel with the ability to manage the consequences of long-COVID and preserve/improve patient quality of life. It has been shown that cardiovascular rehabilitation programs (CRPs) stimulate the parasympathetic nervous system, improve cardiorespiratory fitness (CRF), and reduce cardiovascular risk factors, hospitalization rates, and cognitive impairment in patients suffering from cardiovascular diseases. Given their efficacy in improving patient outcomes, CRPs may have salutary potential for the treatment of cardiovascular sequelae of long-COVID. Indeed, there are several public and private initiatives testing the potential of CRPs in treating fatigue and dysautonomia in long-COVID subjects. The application of these established rehabilitation techniques to COVID-19 cardiovascular syndrome represents a promising approach to improving functional capacity and quality of life. In this brief review, we will focus on the long-lasting cardiovascular and autonomic sequelae occurring after COVID-19 infection, as well as exploring the potential of classic and novel CRPs for managing COVID-19 cardiovascular syndrome. Finally, we expect this review will encourage health care professionals and private/public health organizations to evaluate/implement non-invasive techniques for the management of COVID-19 cardiovascular sequalae.

RESUMEN

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. OBJECTIVE: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. METHODS: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. RESULTS: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. CONCLUSION: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Asunto(s)

RESUMEN

There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation (p < 0.01). Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.

RESUMEN

AIMS: To investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. METHODS: Participants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). RESULTS: Ninety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. CONCLUSION: CAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Asunto(s)

RESUMEN

We investigated endothelial and autonomic nervous functions after bariatric surgery. For this, we prospectively recruited 40 patients for bariatric surgery or medical treatment (20 in each group). Heart rate variability (HRV) and endothelial function were evaluated before and 3 months after treatments. Glucagon-like peptide 1 (GLP-1), insulin, and glucose at fasting and 30 and 60 min after a standard 300-kcal meal were also analyzed. Surgery but not medical care increased HRV in all time-domain variables, while frequency-domain variables, vascular elasticity, and endothelial reactivity did not change. Changes in GLP-1 and insulin resistance markers did not correlate with HRV. After 3 months, bariatric surgery improved the parasympathetic activity of cardiac autonomic function. Trial registration: NCT03911479.

Asunto(s)

RESUMEN

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 106 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 106 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.

Asunto(s)

RESUMEN

A neuropatia autonômica cardíaca (NAC) é uma complicação comum do diabetes mellitus (DM) e frequentemente, subdiagnosticada. A NAC está associada ao aumento da mortalidade, cardiovascular e renal, doença renal crônica e maior morbidade em pacientes com DM. Apesar dessas consequências, muitas vezes, a NAC permanece sem diagnóstico por um período prolongado. Isso geralmente porque a doença é assintomática até a fase avançada, bem como pela falta de informações e de estratégias de triagem. Clinicamente NAC se manifesta por distúrbios funcionais ou condições clínicas que envolvem desajuste das atividades reflexas cardiovasculares, tais como taquicardia em repouso, intolerância ao exercício, hipotensão ortostática, instabilidade cardiovascular intraoperatória, disfunção elétrica do coração traduzida por arritmias e isquemia miocárdica silenciosa. Essas alterações comprometem a qualidade de vida e a sobrevida dos pacientes. A NAC, segundo sua evolução, pode ser subdividida em subclínica (fase em que predominam alterações funcionais reversíveis) e clínica (quando as alterações neuronais estruturais estão plenamente estabelecidas). A avaliação da integridade do sistema nervoso autonômico é realizada por meio de exploração da atividade parassimpática, analisando o comportamento da frequência cardíaca (FC) em resposta à respiração profunda, ortostatismo ou manobra de Valsalva. A atividade simpática é explorada por meio de aferição da pressão arterial em resposta a mudança de postura (ortostatismo) e esforço isométrico. A análise da variabilidade da frequência cardíaca (VFC), no domínio do tempo, no domínio da frequência e por métodos gráficos complementam essa avaliação. Neste artigo de revisão, analisamos recentes informações sobre a epidemiologia, manifestações clínicas, diagnóstico, e tratamentos da NAC

Cardiac autonomic neuropathy (CAN) is a common and often-underdiagnosed complication of diabetes mellitus (DM). CAN is associated with increased mortality, cardiovascular disease, chronic kidney disease, and morbidity in patients with DM, but despite these significant consequences CAN often remains undiagnosed for a prolonged period. This is commonly due to the disease being asymptomatic until the later stages, as well as a lack of easily available screening strategies. Clinically, CAN is manifested by functional disorders or clinical conditions that involve maladjustment of cardiovascular reflex activities, such as tachycardia at rest, exercise intolerance, orthostatic hypotension, intraoperative cardiovascular instability, electrical dysfunction of the heart translated by arrhythmias and silent myocardial ischemia. These changes compromise patients' quality of life and survival. CAN, according to its evolution, can be subdivided into subclinical (phase in which reversible functional changes predominate) and clinical (when structural neuronal changes are fully established). The assessment of the integrity of the autonomic nervous system is performed by exploring parasympathetic activity, analyzing the heart rate in response to deep breathing, orthostatism or Valsalva maneuver. Sympathetic activity is explored by measuring blood pressure in response to a change in posture (orthostatism) and isometric effort. The analysis of heart rate variability (HRV), in the time domain, in the frequency domain and by graphic methods, complement this assessment. In this article, we review the latest developments in the epidemiology, pathogenesis, diagnosis, consequences, and treatments of CAN in patients with DM.

RESUMEN

BACKGROUND: Autonomic dysfunction is a hallmark feature of hereditary ATTR amyloidosis. The aim of this study was to summarize the characteristics and natural history of autonomic dysfunction in patients with hereditary ATTR amyloidosis. METHODS: A systematic review of the natural history and clinical trials of patients with ATTR amyloidosis was performed. Alternative surrogate markers of autonomic function were analyzed to understand the prevalence and outcome of autonomic dysfunction. RESULTS: Patients with early-onset disease displayed autonomic dysfunction more distinctively than those with late-onset disease. The nutritional status and some autonomic items in the quality-of-life questionnaires were used to assess the indirect progression of autonomic dysfunction in most studies. Gastrointestinal symptoms and orthostatic hypotension were resent earlier than urogenital complications. Once symptoms were present, their evolution was equivalent to the progression of the motor and sensory neuropathy impairment. CONCLUSION: The development of autonomic dysfunction impacts morbidity, disease progression, and mortality in patients with hereditary ATTR amyloidosis.

Asunto(s)