Cholinergic stimulation with pyridostigmine, hemodynamic and echocardiographic analysis in healthy subjects

OBJECTIVE: Growing evidence suggests that sudden death after an acute myocardial infarction (AMI) correlates with autonomic nervous system imbalance. Parasympathomimetic drugs have been tested to reverse these changes. However, their effects on ventricular function need specific evaluation. Our objective was to analyze pyridostigmine's (PYR) effect on hemodynamic and echocardiographic variables of ventricular function. METHODS: Twenty healthy volunteers underwent Doppler echocardiographic evaluations, blood pressure (BP), and heart rate (HR) assessment at rest, before and 120 min after ingestion of 30 mg PYR or placebo, according to a double-blind, placebo-controlled, crossed and randomized protocol, on different days. RESULTS: PYR was well tolerated and did not cause alterations in BP or in ventricular systolic function. A reduction in HR of 10.9±1.3% occurred (p<0,00001). There was an A wave reduction in the mitral flow (p<0.01) and an E/A ratio increase (p<0.001) without changes in the other diastolic function parameters (p>0.05). CONCLUSION: PYR reduces HR and increases E/A ratio, without hemodynamic impairment or ventricular function change.

Right ventricular bifocal stimulation in the treatment of dilated cardiomyopathy with heart failure

OBJECTIVE: To describe a new more efficient method of endocardial cardiac stimulation, which produces a narrower QRS without using the coronary sinus or cardiac veins. METHODS: We studied 5 patients with severe dilated cardiomyopathy, chronic atrial fibrillation and AV block, who underwent definitive endocardial pacemaker implantation, with 2 leads, in the RV, one in the apex and the other in the interventricular septum (sub pulmonary), connected, respectively, to ventricular and atrial bicameral pacemaker outputs. Using Doppler echocardiography, we compared, in the same patient, conventional (VVI), high septal ("AAI") and bifocal ("DDT" with AV interval ~ 0) stimulation. RESULTS: The RV bifocal stimulation had the best results with an increase in ejection fraction and cardiac output and reduction in QRS duration, mitral regurgitation and in the left atrium area (p <= 0.01). The conventional method of stimulation showed the worst result. CONCLUSION: These results suggest that, when left ventricular stimulation is not possible, right ventricular bifocal stimulation should be used in patients with severe cardiomyopathy where a pacemaker is indicated.

Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

OBJETIVE: The evaluation, by exercise stress testing, of the cardiorespiratory effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor. METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of hemodynamic and ventilation variables of 10 healthy subjects who underwent three exercise stress tests (the first for adaptation and determination of tolerance to exercise, the other two after administration of placebo or 45mg of PYR). RESULTS: Heart rate at rest was: 68±3 vs 68±3bpm before and after placebo, respectively (P=0.38); 70±2 vs 59±2bpm, before and after pyridostigmine, respectively (P<0.01). During exercise, relative to placebo: a significantly lower heart rate after PYR at, respectively, 20% (P=0.02), 40% (P=0.03), 80% (P=0.05) and 100% (P=0.02) of peak effort was observed. No significant differences were observed in arterial blood pressure, oxygen consumption at submaximal and maximal effort, exercise duration, respiratory ratio, CO2 production, ventilation threshold, minute ventilation, and oxygen pulse. CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Avaliando a atividade vagal cardíaca na eletrocardiografia convencional

OBJETIVO: Determinar a viabilidade da utilização de traçado convencional de eletrocardiografia (ECG) para avaliação da atividade vagal cardíaca (AVC). MÉTODOS: Foram analisados, retrospectivamente, 1.395 indivíduos (995 homens), na faixa de idade de 46 + 17,2 anos (média ± desvio padrão), com traçados de ECG convencional para medida do Delta RR, que representa a diferença, em ms, entre o maior e o menor intervalo RR, e com resultados da avaliação autonômica parassimpática, o teste de exercício de quatro segundos (T4s), que quantifica a AVC por meio do índice vagal cardíaco (IVC). Foram obtidas curvas ROC para determinar os valores de Delta RR com melhor relação entre sensibilidade e especificidade para os pontos de corte de baixa e alta AVC, respectivamente, de 1,20 e 1,95. RESULTADOS: Os valores de delta RR correlacionaram-se significativamente com os de IVC (r = 0,40; p < 0,001). Foram identificados < 60 ms e > 120 ms como os melhores pontos de corte para baixa e alta AVC, com sensibilidade de 75% e 57%, especificidade de 62% e 79% e áreas das curvas ROC de 0,76 e 0,74, respectivamente. CONCLUSÃO: A medida visual do delta RR em um traçado de ECG parece ser válida para a avaliação clínica preliminar e rápida da AVC, podendo ser útil em consultórios, emergências ou situações nas quais o uso de métodos mais sofisticados de avaliação autonômica não seja viável, oportuno ou conveniente.

Normotensos com resposta pressórica exagerada ao exercício possuem tônus vagal cardíaco aumentado

FUNDAMENTO: Valores exagerados da pressão arterial sistólica (PAS) durante um teste cardiopulmonar de exercício máximo (TCPE) são classicamente considerados como inapropriados e associados a um maior risco para desenvolvimento de doenças cardiovasculares. Sabe-se que o sistema nervoso autônomo modula a PA no exercício. Contudo, não está claramente estabelecido o comportamento do tônus vagal cardíaco (TVC) em indivíduos saudáveis com uma resposta pressórica exagerada no TCPE. OBJETIVO: Analisar o comportamento do TVC em homens adultos saudáveis que apresentam uma resposta pressórica exagerada no TCPE. MÉTODOS: De 2.505 casos avaliados entre 2002-2009, foram identificados criteriosamente 154 casos de homens, entre 20-50 anos de idade, saudáveis e normotensos. A avaliação incluía exame clínico, medidas antropométricas, testes de exercício de 4 segundos (tônus vagal cardíaco) e TCPE realizado em cicloergômetro, com medidas de pressão arterial a cada minuto pelo método auscultatório. Baseado no valor máximo de PAS obtido no TCPE, a amostra foi dividida em tercis, comparando-se o TVC, a carga máxima e o VO2 máximo. RESULTADOS: Os valores de TVC diferiram entre os indivíduos que se apresentavam nos tercis inferior e superior para a resposta da PAS ao TCPE, respectivamente, 1,57 ± 0,03 e 1,65 ± 0,04 (média ± erro padrão da média) (p = 0,014). Os dois tercis também diferiam quanto ao VO2 máximo (40,7 ± 1,3 vs 46,4 ± 1,3 ml/kg-1.min-1; p = 0,013) e a carga máxima (206 ± 6,3 vs 275 ± 8,7 watts; p < 0,001). CONCLUSÃO: Uma resposta pressórica exagerada durante o TCPE em homens adultos saudáveis é acompanhada de indicadores de bom prognóstico clínico, incluindo níveis mais altos de condição aeróbica e de tônus vagal cardíaco.

Comparação entre métodos de avaliação da modulação vagal cardíaca

FUNDAMENTO: Diversos métodos têm sido utilizados para avaliar a modulação vagal cardíaca; entretanto, há lacunas quanto a associação e acurácia desses métodos. OBJETIVO: Investigar a associação entre três métodos válidos, reprodutíveis e comumente utilizados para avaliação da modulação vagal cardíaca, e comparar as suas acurácias. MÉTODOS: Trinta homens saudáveis (23 ± 4 anos) e 15 homens com coronariopatia (61 ± 10 anos) foram avaliados em ordem contrabalanceada pela Variabilidade da Frequência Cardíaca (VFC; variáveis: domínio do tempo = pNN50, DPNN e RMSSD, domínio da frequência = AF ms² e AF u.n.), Arritmia Sinusal Respiratória (ASR) e Teste de Exercício de 4 segundos (T4s). RESULTADOS: Indivíduos saudáveis apresentaram maior modulação vagal nos três métodos (p < 0,05). No grupo saudável houve correlação (p < 0,05) entre os resultados da VFC (pNN50 e DPNN) e da ASR, mas não houve correlação entre o T4s e os outros dois métodos estudados. No grupo com coronariopatia houve correlação entre os resultados da VFC (pNN50, DPNN, RMSSD, AF ms² e AF u.n.) e da ASR. Em adição, houve correlação entre o T4s e a ASR. Por fim, os métodos ASR e T4s apresentaram tamanho do efeito mais preciso e melhor acurácia (p < 0,05) comparados à VFC. CONCLUSÃO: A VFC e a ASR geraram resultados parcialmente redundantes em indivíduos saudáveis e em pacientes com coronariopatia, enquanto o T4s gerou resultados complementares a VFC e ASR em indivíduos saudáveis. Além disso, os métodos ASR e T4s foram mais precisos para discriminar a modulação vagal cardíaca entre indivíduos saudáveis e pacientes com coronariopatia comparados à VFC.

Nichtlineare Wechselwirkung im auditorischen Kortex nach Stimulation mit Sequenzen mehrerer Sinustöne

Monkey, neuron, auditory cortex, temporal processing, nonlinear interaction, sequence, temporal coding

Neural dynamics and their relationship to learning behavior in response tot stimulation with a cortical neuroprosthesis

Sensory cortex, neuroprosthetics, brain-machine-interfaces, neurodynamics, learning, perception, embodied cognition

Beeinflussung von auditorischer Objektbildung durch visuelle Stimulation

Streaming, Auditory Scene Analysis, Mismatch Negativity, Auditorische Szenenanalyse, Stream-Segregation

Influence of nucleus accumbens core or shell stimulation on early long-term potentiation in the dentate gyrus of freely moving rats

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Dynamik einiger Neurotransmitter beim räumlichen Lernen und nach elektrischer Stimulation im Hippocampus und Cortex praefrontalis der Ratte

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2010

Indications à la stimulation cardiaque dans la syncope vasovagale [Pacing in vasovagal syncope].

This article presents a critical review of the literature about the potential benefit of cardiac pacing in patients suffering from vasovagal or neurocardiogenic syncope. The manifestation of vasovagal syncope comprises some reflex bradycardia and vasoplegia resulting in cerebral hypoperfusion that ultimately leads to a loss of consciousness. The literature reports conflicting results of the potential benefit of cardiac pacing on the prevention of recurrence of vasovagal events. A detailed analysis of the inclusion criteria of these studies permits to clarify the discrepancy. Only patients older than 50 years with prolonged sinus pause at time of syncope benefit of the implantation of a cardiac pacemaker.

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice.

In the present study, we evaluated stimulation of the angiotensin type 2 receptor (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel therapeutic concept for the treatment of multiple sclerosis using the model of experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21 (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell composition were estimated by immunostaining and FACS analyses of lumbar spinal cords. The in vivo study was complemented by experiments in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction in EAE-induced demyelinated areas in lumbar spinal cord tissue after AT2R stimulation. C21-treated mice had a significantly better neurological score than vehicle-treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ), AT2R stimulation prevented demyelination, accelerated re-myelination and reduced the number of microglia. Cytokine synthesis and nitric oxide production by microglia in vitro were significantly reduced after C21 treatment. These results suggest that AT2R stimulation protects the myelin sheaths in autoimmune central nervous system inflammation by inhibiting the T-cell response and microglia activation. Our findings identify the AT2R as a potential new pharmacological target for demyelinating diseases such as multiple sclerosis.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study.

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.