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2.
Medicine (Baltimore) ; 99(4): e18961, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977913

RESUMO

This study explored whether sympathovagal modulation assessed through frequency domains of heart rate variability (HRV) can indicate sepsis in patients with suspected infection.In total, 370 consecutive adult patients with suspected infection admitted to the emergency department were enrolled in this single-center cohort study. A continuous 10-minute electrocardiography for HRV analysis was recorded immediately for these patients after inclusion. Patients were stratified into non-sepsis and sepsis groups based on a sepsis-related organ failure assessment score of ≥2 that met the Third International Consensus Definitions for Sepsis. Seven frequency domains of HRV were compared between these 2 groups.Compared with the non-sepsis group (n = 98), the sepsis group (n = 272) had a significantly lower incidence of respiratory tract infection, higher total power, higher very-low-frequency component, higher high-frequency (HF) component, higher normalized HF component, lower normalized low-frequency (LF) component, and lower LF component/HF component ratio (LF/HF). Multiple logistic regression model identified HF component (odds ratio [OR] = 0.994; 95% confidence interval [CI], 0.990-0.999) and LF/HF (OR = 0.494; 95% CI, 0.423-0.578) as significant variables associated with sepsis. The area under receiver operating characteristic curves of HF component and LF/HF was 0.741 (95% CI, 0.685-0.797) and 0.930 (95% CI, 0.900-0.960), respectively, in identifying sepsis in patients with suspected infection.Tilted sympathovagal balance toward increased vagal activity and depressed sympathetic modulation, assessed by the HF component and LF/HF, may indicate sepsis in patients with suspected infection.


Assuntos
Frequência Cardíaca , Sepse/diagnóstico , Nervo Vago/fisiopatologia , Idoso , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Estudos Prospectivos , Sensibilidade e Especificidade , Sepse/fisiopatologia
3.
Anesth Analg ; 130(4): 1054-1062, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30346356

RESUMO

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P < .001), and preserved kidney gross morphology and structure and attenuated cell apoptosis after ischemia-reperfusion. Furthermore, Dex also significantly increased acetylcholine release to 135.8 pmol/L (median) when compared to that (84.7 pmol/L) in the sham group (P < .001) and reduced the levels of several inflammatory mediators induced by renal ischemia/reperfusion. All the effects were abolished by vagotomy, splenectomy, or combinative administration of atipamezole, an α2-adrenergic receptor antagonist. CONCLUSIONS: Our findings suggest that Dex provides renoprotection, at least in part, through anti-inflammatory effects of the parasympathetic nervous system activation in addition to its direct actions on α2-adrenergic receptors.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Anti-Inflamatórios/farmacologia , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Nefropatias/prevenção & controle , Sistema Nervoso Parassimpático/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Acetilcolina/sangue , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Apoptose/efeitos dos fármacos , Catecolaminas/sangue , Imidazóis/farmacologia , Mediadores da Inflamação/metabolismo , Rim/patologia , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nervo Vago/fisiopatologia
4.
Brain Stimul ; 13(1): 1-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31668983

RESUMO

Major Depressive Disorder (MDD) is a psychiatric disorder characterized by high comorbidity with cardiovascular disease. Furthermore, a combination of high heart rate (HR) and low heart rate variability (HRV) has been frequently reported in depressed patients. The present review proposes a frontal-vagal (brain-heart) network that overlaps with functional nodes of the depression network. Moreover, we summarize neuromodulation studies that have targeted key nodes in this depression network, with subsequent impact on heart rate (HR) or heart-rate-variability (HRV), such as the dorsolateral prefrontal cortex (DLPFC), subgenual anterior cingulate cortex (sgACC), and the vagus nerve (VN). Based on the interplay of this frontal-vagal network, we emphasize the importance of including HR and HRV measurements in human depression studies, in particular those that conduct neuromodulation, in order to obtain a better understanding of the pathways that are affected, and we explore the possibilities of using this frontal-vagal interplay as a method for target engagement in neuromodulation treatments. This frontal-vagal network theory opens-up the possibility for individualizing neuromodulation treatments such as rTMS. A recent development called Neuro-Cardiac-Guided TMS (NCG-TMS), was developed based on this theory, and an individual-participant meta-analysis is presented. Four studies provide consistent and replicable support for NCG-TMS as a target engagement method, with consistent HR deceleration during frontal TMS and HR acceleration during motor strip TMS.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Frequência Cardíaca/fisiologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Nervo Vago/fisiopatologia , Giro do Cíngulo/fisiopatologia , Humanos , Córtex Motor/fisiopatologia
5.
Nutrients ; 11(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717368

RESUMO

(1) High-fat (HF) diet leads to gut microbiota dysbiosis which is associated with systemic inflammation. Bacterial-driven inflammation is sufficient to alter vagally mediated satiety and induce hyperphagia. Promoting bacterial fermentation improves gastrointestinal (GI) epithelial barrier function and reduces inflammation. Resistant starch escape digestion and can be fermented by bacteria in the distal gut. Therefore, we hypothesized that potato RS supplementation in HF-fed rats would lead to compositional changes in microbiota composition associated with improved inflammatory status and vagal signaling. (2) Male Wistar rats (n = 8/group) were fed a low-fat chow (LF, 13% fat), HF (45% fat), or an isocaloric HF supplemented with 12% potato RS (HFRS) diet. (3) The HFRS-fed rats consumed significantly less energy than HF animals throughout the experiment. Systemic inflammation and glucose homeostasis were improved in the HFRS compared to HF rats. Cholecystokinin-induced satiety was abolished in HF-fed rats and restored in HFRS rats. HF feeding led to a significant decrease in positive c fiber staining in the brainstem which was averted by RS supplementation. (4) The RS supplementation prevented dysbiosis and systemic inflammation. Additionally, microbiota manipulation via dietary potato RS prevented HF-diet-induced reorganization of vagal afferent fibers, loss in CCK-induced satiety, and hyperphagia.


Assuntos
Bactérias/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Suplementos Nutricionais , Disbiose , Microbioma Gastrointestinal , Inflamação/prevenção & controle , Intestinos/inervação , Intestinos/microbiologia , Obesidade/prevenção & controle , Solanum tuberosum , Amido/administração & dosagem , Nervo Vago/fisiopatologia , Ração Animal , Animais , Bactérias/metabolismo , Encéfalo/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Comportamento Alimentar , Fermentação , Hiperfagia/metabolismo , Hiperfagia/microbiologia , Hiperfagia/fisiopatologia , Hiperfagia/prevenção & controle , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/fisiopatologia , Masculino , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/fisiopatologia , Raízes de Plantas , Ratos Wistar , Resposta de Saciedade , Amido/metabolismo , Nervo Vago/metabolismo , Ganho de Peso
6.
Circ Arrhythm Electrophysiol ; 12(10): e007281, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31610720

RESUMO

BACKGROUND: Ganglionated plexi (GPs) play an important role in both the initiation and maintenance of atrial fibrillation (AF). GPs can be located by using continuous high-frequency stimulation (HFS) to elicit a vagal response, but whether the vagal response phenomenon is common to patients without AF is unknown. METHODS: HFS of the left atrial GPs was performed in 42 patients (aged 58.0±10.2 years) undergoing ablation for AF and 21 patients (aged 53.2±12.8 years) undergoing ablation for a left-sided accessory pathway. The HFS (20 Hz, 25 mA, 10-ms pulse duration) was applied for 5 seconds at 3 sites within the presumed anatomic area of each of the 5 major left atrial GPs (for a total of 15 sites per patient). We defined vagal response to HFS as prolongation of the R-R interval by >50% in comparison to the mean pre-HFS R-R interval averaged over 10 beats and active-GP areas as areas in which a vagal response was elicited. RESULTS: Overall, more active-GP areas were found in the AF group patients than in the non-AF group patients, and at all 5 major GPs, the maximum R-R interval during HFS was significantly prolonged in the AF patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of AF. Conclusions The significant increase in vagal responses elicited in patients with AF compared with responses in non-AF patients suggests that vagal responses to HFS reflect abnormally increased GP activity specific to AF substrates.


Assuntos
Fibrilação Atrial/terapia , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Estimulação do Nervo Vago/métodos , Nervo Vago/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/métodos , Feminino , Seguimentos , Sistema de Condução Cardíaco/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Artigo em Inglês | MEDLINE | ID: mdl-31652709

RESUMO

Lower cardiac vagal control (CVC), which is often understood as an indicator for impaired regulatory processes, is assumed to predict the development of depressive symptoms. As this link has not been consistently demonstrated, sleep quality has been proposed as a moderating factor. However, previous studies were limited by non-representative samples, cross-sectional data, and focused on CVC as a physiological indicator for impaired regulatory processes, but neglected corresponding subjective measures. Therefore, we investigated whether sleep quality moderates the effects of CVC (quantified by high-frequency heart rate variability) and self-reported regulatory processes (self- and emotion-regulation) on concurrent depressive symptoms and on depressive symptoms after three months in a representative sample (N = 125). Significant interactions between CVC and sleep quality (in women only), as well as self-/emotion-regulation and sleep quality emerged, whereby higher sleep quality attenuated the relation between all risk factors and current depressive symptoms (cross-sectional data). However, there were no significant interactions between those variables in predicting depressive symptoms three months later (longitudinal data). Our cross-sectional findings extend previous findings on sleep quality as a protective factor against depressive symptoms in the presence of lower CVC and subjective indices of impaired regulatory processes. In contrast, our conflicting longitudinal results stress the need for further investigations.


Assuntos
Depressão/fisiopatologia , Frequência Cardíaca/fisiologia , Sono/fisiologia , Nervo Vago/fisiopatologia , Adolescente , Adulto , Estudos Transversais , Depressão/etiologia , Depressão/prevenção & controle , Depressão/psicologia , Feminino , Humanos , Masculino , Fatores de Proteção , Fatores de Risco , Autorrelato , Autocontrole , Adulto Jovem
8.
Neurol Clin ; 37(4): 847-869, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31563236

RESUMO

The trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes all marked by unilateral headache and ipsilateral cranial autonomic features. The TACs include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, and hemicrania continua. Pathophysiology includes the trigeminal pain system, autonomic system, hypothalamus, and more recently an identified role for the vagus nerve. Diagnosis is made after looking at headache frequency, duration, and accompanying symptoms. Each TAC has its own unique treatment, which is discussed in depth.


Assuntos
Cefalalgias Autonômicas do Trigêmeo/tratamento farmacológico , Cefalalgias Autonômicas do Trigêmeo/fisiopatologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Diagnóstico Diferencial , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Cefaleia/fisiopatologia , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Indometacina/administração & dosagem , Carbonato de Lítio/administração & dosagem , Melatonina/administração & dosagem , Cefalalgias Autonômicas do Trigêmeo/diagnóstico , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia
9.
Br J Anaesth ; 123(6): 758-767, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31492527

RESUMO

BACKGROUND: Myocardial injury is more frequent after noncardiac surgery in patients with preoperative cardiac vagal dysfunction, as quantified by delayed heart rate (HR) recovery after cessation of cardiopulmonary exercise testing. We hypothesised that serial and dynamic measures of cardiac vagal activity are also associated with myocardial injury after noncardiac surgery. METHODS: Serial autonomic measurements were made before and after surgery in patients undergoing elective noncardiac surgery. Cardiac vagal activity was quantified by HR variability and HR recovery after orthostatic challenge (supine to sitting). Revised cardiac risk index (RCRI) was calculated for each patient. The primary outcome was myocardial injury (high-sensitivity troponin ≥15 ng L-1) within 48 h of surgery, masked to investigators. The exposure of interest was cardiac vagal activity (high-frequency power spectral analysis [HFLn]) and HR recovery 90 s from peak HR after the orthostatic challenge. RESULTS: Myocardial injury occurred in 48/189 (25%) patients, in whom 41/48 (85%) RCRI was <2. In patients with myocardial injury, vagal activity (HFLn) declined from 5.15 (95% confidence interval [CI]: 4.58-5.72) before surgery to 4.33 (95% CI: 3.76-4.90; P<0.001) 24 h after surgery. In patients who remained free of myocardial injury, HFLn did not change (4.95 [95% CI: 4.64-5.26] before surgery vs 4.76 [95% CI: 4.44-5.08] after surgery). Before and after surgery, the orthostatic HR recovery was slower in patients with myocardial injury (5 beats min-1 [95% CI: 3-7]), compared with HR recovery in patients who remained free of myocardial injury (10 beats min-1 [95% CI: 7-12]; P=0.02). CONCLUSIONS: Serial HR measures indicating loss of cardiac vagal activity are associated with perioperative myocardial injury in lower-risk patients undergoing noncardiac surgery.


Assuntos
Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Procedimentos Cirúrgicos Operatórios , Nervo Vago/fisiopatologia , Idoso , Estudos de Coortes , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
PLoS One ; 14(8): e0221277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433825

RESUMO

BACKGROUND: Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery. METHODS: In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min-1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals). RESULTS: 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14-1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05-1.62);p = 0.02)), infective (OR:1.38 (1.10-1.72); p = 0.006), renal (OR:1.91 (1.30-2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15-1.69); p<0.001)), neurological (OR:1.73 (1.11-2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14-1.68); p = 0.001) within 5 days of surgery. CONCLUSIONS: Multi-organ dysfunction is more common in surgical patients with cardiac vagal dysfunction, defined as HRR ≤ 12 bpm after preoperative cardiopulmonary exercise testing. CLINICAL TRIAL REGISTRY: ISRCTN88456378.


Assuntos
Teste de Esforço , Traumatismos Cardíacos/fisiopatologia , Frequência Cardíaca , Complicações Pós-Operatórias/fisiopatologia , Nervo Vago/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Niger J Physiol Sci ; 34(1): 115-119, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449280

RESUMO

Decreased physical activity, increased psychosocial stress and work stress have contributed to the increased prevalence of obesity and Hypertension (HTN). Irrespective of the aetiology, sympathetic over activity has been recognized as the main pathophysiologic mechanism in the genesis of obesity and HTN. Sympathovagal imbalance or dysregulation of autonomic functions owing to sympathetic over activity and vagal withdrawal is reported to be the basis of many clinical disorders. Obesity, hypertension and diabetes mellitus are known to be associated with dysregulation of autonomic functions independently. Heart Rate Variability (HRV) has emerged as a practical, non-invasive tool to quantitatively investigate cardiac autonomic dysregulation. The present study was undertaken to ascertain whether obesity has any effect on further disruption of autonomic functions particularly in hypertensive patients. A total of 96 male and female adults aged between 40-50 years visiting the Primary Health Centre, Yelwala, Mysuru district, India were recruited for this study. They were grouped in to 3 (n=32) as Groups I (Obese hypertensive), II (non-obese hypertensive) and II (non-obese normotensive, control), HRV was determined using the One minute during deep breathing method. Data were presented as Mean ± SD, inferential statistics was by One Way ANOVA and Tukey's Post Hoc test p value <0.005 at α0.05 HRV was significantly decreased in obese hypertensive patients compared to the non-obese hypertensive patients. Our present study supports that obesity and hypertension probably has additive effect in causing autonomic dysregulation.


Assuntos
Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Obesidade/epidemiologia , Obesidade/fisiopatologia , Vigilância da População , Nervo Vago/fisiopatologia , Adulto , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/diagnóstico , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Vigilância da População/métodos , Sistema Nervoso Simpático/fisiopatologia
12.
Auton Neurosci ; 221: 102577, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31445407

RESUMO

The present study aimed to compare linear and symbolic dynamics (SD) indices for detecting the autonomic cardiac changes produced by endotoxemia in freely-moving rats. In this context, we analyzed ECG-derived R-R time series in freely moving Dark Agouti rats, which received lipopolysaccharide (LPS, n = 9), or vehicle (V, n = 7). Five minutes R-R time series were assessed every hour up to +12 h and + 24 h post-LPS injection. We found that SD indices showed significant differences at +7 h between V vs. LPS groups and at +9 h between basal levels of LPS (-3 h) and post-LPS injection (pre-LPS vs. post-LPS). In general, SD seems more appropriate than linear indices to evaluate the autonomic changes of endotoxemic rats. Overall, the symbolic parameters detected decreased R-R variability and complexity, which indicate a modification of the autonomic regulation during LPS-induced endotoxemia. This modification is probably related to a reduced activity of the cholinergic anti-inflammatory pathway at the long term.


Assuntos
Endotoxemia/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Nervo Vago/fisiopatologia , Animais , Endotoxemia/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Dinâmica não Linear , Ratos , Ratos Endogâmicos
13.
World Neurosurg ; 131: 191-193, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394364

RESUMO

BACKGROUND: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy; however, the misplacement of electrodes may cause complications and thus needs to be avoided. METHODS: We herein report an intraoperative monitoring technique to prevent the misplacement of electrodes. Endotracheal tube electrodes were inserted to record electromyographic activity from the vocal cords and identify the vagus nerve. Electromyography electrodes were placed on the sternomastoid muscle, sternohyoid muscle, geniohyoid muscle, and trapezius muscle to record muscle activities innervated by the ansa cervicalis. The vagus nerve and ansa cervicalis were electrically stimulated during surgery, and electromyography of the vocal cords and muscles innervated by the ansa cervicalis was recorded. The threshold of vagus nerve activation ranged between 0.05 and 0.75 mA. RESULTS: The vagus nerve was successfully identified and differentiated from the nerve root of the ansa cervicalis using this technique. CONCLUSIONS: Intraoperative monitoring of the vagus nerve and ansa cervicalis is useful for safe and effective vagus nerve stimulation.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Estimulação do Nervo Vago , Adolescente , Adulto , Idoso , Criança , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Nervo Vago/fisiopatologia , Nervo Vago/cirurgia , Estimulação do Nervo Vago/métodos , Prega Vocal/fisiopatologia , Adulto Jovem
14.
Am J Physiol Heart Circ Physiol ; 317(3): H607-H616, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31322427

RESUMO

Mechanisms behind development of premature ventricular contraction (PVC)-induced cardiomyopathy remain unclear. PVCs may adversely modulate the autonomic nervous system to promote development of heart failure. Afferent neurons in the inferior vagal (nodose) ganglia transduce cardiac activity and modulate parasympathetic output. Effects of PVCs on cardiac parasympathetic efferent and vagal afferent neurotransmission are unknown. The purpose of this study was to evaluate effects of PVCs on vagal afferent neurotransmission and compare these effects with a known powerful autonomic modulator, myocardial ischemia. In 16 pigs, effects of variably coupled PVCs on heart rate variability (HRV) and vagal afferent neurotransmission were evaluated. Direct nodose neuronal recordings were obtained in vivo, and cardiac-related afferent neurons were identified based on their response to cardiovascular interventions, including ventricular chemical and mechanical stimuli, left anterior descending (LAD) coronary artery occlusion, and variably coupled PVCs. On HRV analysis before versus after PVCs, parasympathetic tone decreased (normalized high frequency: 83.6 ± 2.8 to 72.5 ± 5.3; P < 0.05). PVCs had a powerful impact on activity of cardiac-related afferent neurons, altering activity of 51% of neurons versus 31% for LAD occlusion (P < 0.05 vs. LAD occlusion and all other cardiac interventions). Both chemosensitive and mechanosensitive neurons were activated by PVCs, and their activity remained elevated even after cessation of PVCs. Cardiac afferent neural responses to PVCs were greater than any other intervention, including ischemia of similar duration. These data suggest that even brief periods of PVCs powerfully modulate vagal afferent neurotransmission, reflexly decreasing parasympathetic efferent tone.NEW & NOTEWORTHY Premature ventricular contractions (PVCs) are common in many patients and, at an increased burden, are known to cause heart failure. This study determined that PVCs powerfully modulate cardiac vagal afferent neurotransmission (exerting even greater effects than ventricular ischemia) and reduce parasympathetic efferent outflow to the heart. PVCs activated both mechano- and chemosensory neurons in the nodose ganglia. These peripheral neurons demonstrated adaptation in response to PVCs. This study provides additional data on the potential role of the autonomic nervous system in PVC-induced cardiomyopathy.


Assuntos
Cardiomiopatias/etiologia , Frequência Cardíaca , Coração/inervação , Contração Miocárdica , Nervo Vago/fisiopatologia , Complexos Ventriculares Prematuros/complicações , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Células Quimiorreceptoras/metabolismo , Modelos Animais de Doenças , Mecanorreceptores/metabolismo , Isquemia Miocárdica/complicações , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Gânglio Nodoso/metabolismo , Gânglio Nodoso/fisiopatologia , Sus scrofa , Transmissão Sináptica , Fatores de Tempo , Nervo Vago/metabolismo , Complexos Ventriculares Prematuros/metabolismo , Complexos Ventriculares Prematuros/fisiopatologia
15.
Ann N Y Acad Sci ; 1454(1): 42-55, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31268181

RESUMO

With few effective treatments available, the global rise of metabolic diseases, including obesity, type 2 diabetes mellitus, and cardiovascular disease, seems unstoppable. Likely caused by an obesogenic environment interacting with genetic susceptibility, the pathophysiology of obesity and metabolic diseases is highly complex and involves crosstalk between many organs and systems, including the brain. The vagus nerve is in a key position to bidirectionally link several peripheral metabolic organs with the brain and is increasingly targeted for neuromodulation therapy to treat metabolic disease. Here, we review the basics of vagal functional anatomy and its implications for vagal neuromodulation therapies. We find that most existing vagal neuromodulation techniques either ignore or misinterpret the rich functional specificity of both vagal efferents and afferents as demonstrated by a large body of literature. This lack of specificity of manipulating vagal fibers is likely the reason for the relatively poor beneficial long-term effects of such therapies. For these therapies to become more effective, rigorous validation of all physiological endpoints and optimization of stimulation parameters as well as electrode placements will be necessary. However, given the large number of function-specific fibers in any vagal branch, genetically guided neuromodulation techniques are more likely to succeed.


Assuntos
Doenças Metabólicas/terapia , Nervo Vago/fisiopatologia , Animais , Estimulação Elétrica , Humanos , Doenças Metabólicas/fisiopatologia , Bloqueio Nervoso , Obesidade/fisiopatologia , Obesidade/terapia
16.
Expert Rev Med Devices ; 16(8): 675-682, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31306049

RESUMO

Introduction: Cardiovascular diseases are accompanied by autonomic nervous system (ANS) imbalance which is characterized by decreased vagal tone. Preclinical and clinical studies have revealed that increasing vagal activity via vagus nerve stimulation (VNS) could protect the heart. Based on these studies, VNS has emerged as a potential non-pharmaceutical treatment strategy. Although it's still difficult to find the optimal stimulus parameters, however, in arrhythmia model, it is reported that low-level VNS (LL-VNS) exacts paradoxical effects from the high-level VNS. Thus, the concept of LL-VNS is introduced. Areas covered: Animal and human studies have discussed the safety and efficacy of VNS and LL-VNS, and this review will discuss the research data in cardiovascular diseases, including atrial arrhythmia, ventricular arrhythmia, ischemia/reperfusion injury, heart failure, and hypertension. Expert opinion: In this regard, various clinical studies have been performed to verify the safety and efficacy of VNS. It is shown that VNS is well-tolerated and safe, but the results of its efficacy are conflicting, which may well block the translational process of VNS. The appearance of LL-VNS brings new idea and inspiration, suggesting an important role of subthreshold stimulation. A better understanding of the LL-VNS will contribute to translational research of VNS.


Assuntos
Doenças Cardiovasculares/terapia , Estimulação do Nervo Vago/métodos , Animais , Encéfalo/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Nervo Vago/fisiopatologia
17.
Circ Arrhythm Electrophysiol ; 12(6): e006942, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31164004

RESUMO

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.


Assuntos
Apneia/terapia , Fibrilação Atrial/prevenção & controle , Diterpenos/farmacologia , Gânglios Simpáticos/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Coração/inervação , Simpatectomia Química/métodos , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Vias Aferentes/fisiopatologia , Animais , Apneia/complicações , Apneia/metabolismo , Apneia/fisiopatologia , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Cães , Gânglios Simpáticos/metabolismo , Gânglios Simpáticos/fisiopatologia , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/metabolismo , Nervo Vago/fisiopatologia
18.
Brain Dev ; 41(9): 769-775, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31056231

RESUMO

BACKGROUND: The Polyvagal theory argues that behavioral modulation is a fundamental neurodevelopmental process that depends on autonomic regulation. OBJECTIVE: The present study aimed to assess sleep architecture in newborns with fetal growth restriction (FGR) using polysomnography as an indicator of Polyvagal theory. METHODS: We studied polysomnography recordings from 68 preterm infants, 34 with FGR and 34 born with appropriate growth for gestational age (AGA), who were matched according to the corrected age for prematurity (CA). Total sleep time, arousals, the percentage of quiet sleep, active sleep, indeterminate sleep, and heart rate were compared between the groups. Linear multiple regression analyses were used to evaluate polysomnography data for the FGR and AGA groups. RESULTS: Average heart rate was significantly lower in most FGR groups compared with AGA groups, and small to large effect sizes were observed in several sleep responses when comparing these groups. In the lineal regression model the CA explains significantly the differences in heart rate, controlled by FGR (p = .012). Additionally, there was evidence that sleeping states show similar trends, that is, increases in quiet and indeterminate sleep, as well as decreases in active sleep when CA was controlled by FGR. CONCLUSION: FGR probably intensifies the unfavorable effect of preterm birth in the responses evaluated by polysomnography. It seems that FGR is associated with alteration in sleep regulation and with differences in heart rate modulation, which may serve as a strategy to preserve energy and such differences likely underlie neurodevelopmental impairments in affected newborns.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Recém-Nascido Prematuro/fisiologia , Polissonografia , Sono/fisiologia , Estudos Transversais , Feminino , Frequência Cardíaca/fisiologia , Humanos , Recém-Nascido , Masculino , Modelos Biológicos , Nervo Vago/crescimento & desenvolvimento , Nervo Vago/fisiopatologia
19.
Am J Physiol Regul Integr Comp Physiol ; 317(2): R337-R345, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116019

RESUMO

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15-55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (ef-GSNA), but not the efferent vagal nerve activity, increased only at the early phase (1-10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis.


Assuntos
Anafilaxia/fisiopatologia , Estômago/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Nervo Vago/fisiopatologia , Anafilaxia/induzido quimicamente , Animais , Barorreflexo , Hipotensão/fisiopatologia , Masculino , Neurônios Eferentes , Nitroprussiato/farmacologia , Ratos Sprague-Dawley , Estômago/inervação , Nervo Vago/fisiologia , Resistência Vascular/fisiologia
20.
Am J Physiol Gastrointest Liver Physiol ; 317(1): G1-G7, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042398

RESUMO

The majority of patients with Parkinson's disease (PD) experience gastrointestinal dysfunction. Recently, we described a nigro-vagal pathway that uses dopaminergic (DA) inputs to the dorsal motor nucleus of the vagus (DMV) and A2 area neurons to modulate gastric motility and tone. This pathway is disrupted in a rodent model of PD. The aim of the present study was to test the hypothesis that brain-stem DA modulation of gastric tone and motility is altered in a rodent model of PD. Male Sprague-Dawley rats received three weekly intraperitoneal injections of paraquat (10 mg/kg) or saline (control). In naive conditions, microinjection of DA into the DMV induced a gastroinhibitory response in 100% of animals. In 19 of 28 PQ-treated animals, however, microinjection of DA into the DVC induced a biphasic response, with an initial increase in gastric tone and motility followed by a profound gastroinhibition. The excitatory response to DA microinjection was attenuated by a combination of DA type 1 (DA1)- and DA2-like receptor antagonists. Conversely, the inhibitory response was reduced by the DA2-like receptor antagonist only. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not modulate the response to DA, thus excluding involvement of the A2 area. At the end of the experiments, induction of the Parkinson phenotype was confirmed by the presence of α-synuclein immunoreactivity in the DMV and substantia nigra pars compacta. These data suggest a maladaptive neural plasticity in brain-stem vagal circuits regulating gastric motility in PQ-treated rats that may be responsible for the gastric dysfunction observed in PD models. NEW & NOTEWORTHY After paraquat treatment and induction of Parkinson's disease, brain-stem dopamine (DA) application induces a biphasic gastric response in the majority of rats, with an initial increase in tone and motility followed by gastroinhibition. The initial increase in gastric tone and motility is mediated via a combined activation of DA type 1 (DA1)- and DA2-like receptors. The inhibitory effects of DA are mediated by DA2-like receptors and are not affected by blockade of adrenergic inputs mediated by α2-adrenoceptors.


Assuntos
Tronco Encefálico/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Motilidade Gastrointestinal , Plasticidade Neuronal , Transtornos Parkinsonianos/metabolismo , Estômago/inervação , Nervo Vago/metabolismo , Animais , Tronco Encefálico/fisiopatologia , Modelos Animais de Doenças , Masculino , Inibição Neural , Paraquat , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Nervo Vago/fisiopatologia
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