Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats / 中华男科学杂志

Objective@#To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms.@*METHODS@#Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP.@*RESULTS@#Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA.@*CONCLUSIONS@#MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.

Analgesia Nociception Index for perioperative analgesia monitoring in spinal surgery / Índice de analgesia/nocicepção para monitorização da analgesia perioperatória na cirurgia da coluna vertebral

Abstract Background and objectives: The Analgesia Nociception Index is an index used to measure the levels of pain, sympathetic system activity and heart rate variability during general anesthesia. In our study, Analgesia Nociception Index monitoring in two groups who had undergone spinal stabilization surgery and were administered propofol-remifentanil (Total Intravenous Anesthesia) and sevoflurane-remifentanyl anesthesia was compared regarding its significance for prediction of postoperative early pain. Methods: BIS and Analgesia Nociception Index monitoring were conducted in the patients together with standard monitoring. During induction, fentanyl 2 µg.kg-1, propofol 2.5 mg.kg-1 and rocuronium 0.6 mg.kg-1 were administered. During maintenance, 1.0 MAC sevoflurane + remifentanil 0.05-0.3 µg.kg-1.min-1 and propofol 50-150 µg.kg-1.min-1 + remifentanil 0.05-0.3 µg.kg-1.min-1 were administered in Group S and Group T, respectively. Hemodynamic parameters, BIS and Analgesia Nociception Index values were recorded during surgery and 30 min postoperatively. Postoperative visual analog scale (VAS) values at 30 minutes were recorded. Results: While no difference was found between mean Analgesia Nociception Index at all times of measurement in both groups, Analgesia Nociception Index measurements after administration of perioperative analgesic drug were recorded to be significantly higher compared to baseline values in both groups. There was correlation between mean values of Analgesia Nociception Index and VAS after anesthesia. Conclusion: Analgesia Nociception Index is a valuable parameter for monitoring of perioperative and postoperative analgesia. In spine surgery, similar analgesia can be provided in both Total Intravenous Anesthesia with remifentanil and sevoflurane administration. Analgesia Nociception Index is efficient for prediction of the need for analgesia during the early postoperative period, and therefore is the provision of patient comfort.

Resumo Justificativa e objetivos: O índice de analgesia/nocicepção (ANI) é usado para medir os níveis de dor, a atividade do sistema simpático e a variabilidade da frequência cardíaca durante a anestesia geral. Em nosso estudo, a monitoração do ANI em dois grupos que foram submetidos à cirurgia de estabilização da coluna vertebral e receberam propofol-remifentanil (Total Intravenous Anesthesia - TIVA) e sevoflurano-remifentanil foram comparados para identificar sua importância na previsão precoce de dor no pós-operatório. Métodos: Os pacientes foram monitorados com o uso de BIS e ANI juntamente com a monitoração padrão. Durante a indução, fentanil (2 µg.kg-1), propofol (2,5 mg.kg-1) e rocurônio (0,6 mg.kg-1) foram administrados. Durante a manutenção, 1 CAM de sevoflurano + remifentanil (0,05-0,3 µg.kg-1.min-1) e propofol (50-150 µg.kg-1.min-1) + remifentanil (0,05-0,3 µg.kg-1.min-1) foram administrados aos grupos S e T, respectivamente. Parâmetros hemodinâmicos, valores de BIS e ANI foram registrados durante a cirurgia e aos 30 minutos de pós-operatório. Os valores escala visual analógica (EVA) aos 30 minutos de pós-operatório foram registrados. Resultados: Enquanto não observamos diferença entre as médias do ANI em todos os tempos de mensuração de ambos os grupos, as mensurações do ANI após a administração do analgésico no perioperatório foram significativamente maiores do que os valores basais de ambos os grupos. Houve correlação entre as médias dos valores de ANI e EVA após a anestesia. Conclusão: ANI é um parâmetro importante para o monitoração de analgesia nos períodos perioperatório e pós-operatório. Na cirurgia da coluna vertebral, analgesia semelhante pode ser obtida com anestesia intravenosa total com remifentanil e com a administração de sevoflurano. O ANI é eficiente para prever a necessidade de analgesia durante o período pós-operatório imediato e, portanto, para proporcionar conforto ao paciente.

Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study / Frequência Cardíaca Elevada está Associada com Desnervação Cardíaca em Pacientes com Insuficiência Cardíaca: Um Estudo com Cintilografia Miocárdica com 123-Iodo-MIBG

Abstract Background: In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood. Objective: To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Method: Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Results: Mean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001). Conclusion: Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation.

Resumo Fundamento: No SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial, ou Estudo do Tratamento da Insuficiência Cardíaca Sistólica com o Inibidor de If Ivabradina), a redução da frequência cardíaca (FC) com ivabradina associou-se com melhor sobrevida e redução das hospitalizações em pacientes com insuficiência cardíaca (IC). Os mecanismos pelos quais a FC elevada aumenta a mortalidade não são totalmente compreendidos. Objetivo: Avaliar a relação da FC basal com atividade clínica, neuro-hormonal e simpática cardíaca em pacientes com IC crônica e FC elevada. Método: Pacientes com IC crônica em ritmo sinusal e FC≥70 apesar de tratamento adequado foram incluídos em um estudo duplo-cego, randomizado, que comparou ivabradina com piridostigmina. Este artigo refere-se a dados basais dos primeiros 16 pacientes. A FC basal (antes da randomização para um dos medicamentos) foi avaliada, e os pacientes classificados em dois grupos, com FC abaixo ou acima dos valores médios. A atividade simpática cardíaca foi avaliada por cintilografia com metaiodobenzilguanidina marcada com iodo 123. Resultados: A FC média foi 83,5±11,5 bpm (intervalo 72 a 104), e sete pacientes (43.7%) tinham FC acima da média. Esses pacientes apresentaram menor distância percorrida no teste de caminhada de 6 minutos (292,3±93 vs 465,2±97,1 m, p=0,0029), valores mais altos de N-terminal do pró-BNP (mediana 708,4 vs 76,1, p=0,035) e menor relação coração/mediastino tardia, indicando desnervação cardíaca (1,48±0,12 vs 1,74±0,09, p<0,001). Conclusão: A FC de repouso elevada em pacientes com IC em tratamento médico adequado associou-se com desnervação cardíaca, pior capacidade funcional e ativação neuro-hormonal.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Practice of Indian Physicians Towards Use of Calcium Channel Blockers in the Management of Hypertension : A Paper Based Questionnaire Survey.

Hypertension is a prevalent condition. Improving blood pressure control would depend on understanding concerns and limitations of physicians. Objective: Understanding practice of calcium channel blockers use among physicians. Material and methods: A cross-sectional, observational paper based questionnaire survey among 218 Indian physicians. Results: According to 55.83% of physicians (n=218), prevalence of hypertension ranges between 21-40%. Sixty percent physicians get referred cases mostly from the general physicians (69.48%). More than 20% patients have concomitant illness according to 33.81% physicians, most common being diabetes (33.44%).According to 96.30% physicians, due to asymptomatic nature, hypertension remains undiagnosed, untreated and uncontrolled. Stress (32.35%), obesity (23.13%), physical inactivity (22.78%) and smoking (20.52%) are responsible for sympathetic over activity. Calcium channel blockers (CCBs) (37.19%), beta blockers (30.43%), angiotensin receptor blocker (ARB) (12.14%) and angiotensin converting enzyme (ACE) inhibitors (4.02%) are used as first choice in patients with sympathetic over activity. Ischemic event, stroke, heart failure and renal failure occur due to ignoring sympathetic over activity according to 30.91%, 25.39%, 20.97% and 22.30% physicians respectively. According to 51.63% of physicians, patient compliance to antihypertensive therapy is > 70%. Lack of awareness (40.5%) and dosage frequency (24%) are two most common reasons for noncompliance. According to 89.72% of physicians, the current CCBs primarily inhibit L-type calcium channels but cause sympathetic over activity. A total of 48.34% physicians, >10% patients complain of pedal edema with amlodipine. In physicians opinion, blockage of L and N type of calcium channels (56.47%), unique mode of action (11.76%), arteriolar and venous dilation (9.41%) and inhibition of reninangiotensin- aldosterone (RAS) system (7.06%) are responsible for less pedal edema with cilnidipine. A total of 98.7% and 99.54% physicians rated efficacy and safety of cilnidipine as “good-very good” compared to other CCB respectively. Conclusion: In hypertension, sympathetic over activity may cause many complications. As per the physicians opinion survey, cilnidipine because of its unique mechanism of action offers multiple benefits in hypertensive patients and can be preferred over amlodipine.

Atividade nervosa simpática e desenvolvimento de lesões de órgãos-alvo na hipertensão arterial: benefícios autonômicos induzidos pelo treinamento aeróbio / Sympathetic nerve activity and development of end-organ injury in hypertension: autonomic benefits induced by aerobic training

A disfunção autonômica encontra-se estreitamente associada ao estabe- lecimento da hipertensão arterial, sendo caracterizada por aumento da atividade simpática, redução do tônus vagal e disfunção barorreflexa, contribuindo para a instalação da insuficiência cardíaca, do infarto do miocárdio, do acidente vascular cerebral, entre outras comorbidades. Remodelamento hipertrófico de arteríolas cerebrais, ativação de quimiorreceptores, anormalidades na barreira hematoencefálica e aumento da atividade neuronal determinam a geração de espécies reativas de oxigênio e citocinas pró-inflamatórias em áreas de controle cardiovascular, as quais, em associação com a hiperativação do sistema renina-angiotensina, perpetuam a disfunção autonôrnica e favorecem a manutenção da hipertensão arterial crônica. Além disto, a disfunção barorreflexa aumenta a variabilidade da pressão arterial, predispondo à rarefação capilar e determinando a progressão de lesões de órgãos-alvo. Por sua vez, a maior disponibilidade de angiotensina li nos diferentes tecidos é um importante estímulo para a inflamação tecidual e hipertrofia de artérias/arteríolas periféricas, potencializando os efeitos deletérios desencadeados pela hiperatividade simpática e disfunção barorreflexa. A hipertensão, uma vez estabelecida, é uma doença crônica que exige tratamento continuado, o qual pode reduzir os níveis pressóricos, mas não curá-Ia. Um importante avanço no controle da hipertensão foi a constatação de que o treinamento aeróbio, mesmo não normalizando a pressão arterial, reduz acentuadamente o estresse oxidativo e a in- flamação em áreas autonômicas, corrigindo prontamente a disfunção barorreflexa, aumentando o tônus vaga I e reduzindo a atividade simpá- tica. Estas adaptações autonôrnicas, em associação com a reversão do remodelamento hipertrófico arteriolar em tecidos exercitados, reduzem a resistência vascular periférica e a pressão arterial.

Autononic dysfunction is closely related to the development of hypertension, being characterized by increased sympathetic activity, decreased vagal tonus and baroreflex dysfunction. These autonornic adaptations contribute to heart failure, myocardial infarction and stroke as well. Hypertrophic remodeling ofbrain arterioles, chemoreceptors activation, blood-brain barrier abnormalities determine reactive oxygen species and pro-inflammatory cytokines production and increased neuronal activity within autonornic brain areas controlling the cardiovascular system. These responses associated with hyperactivation ofthe renin-angiotensin system allow the maintenance of chronic hypertension. Furthermore, baroreflex dysfunction increases arterial pressure variability that causes capillary rarefaction and end-organs injuries. On several tissues, increased Angiotensin li production is an important stimulus for tissue inflammation and arteries/arterioles hypertrophy, thus potentiating the deleterious effects of sympathetic hyperactivity and baroreflex dysfunction. Once established, hypertension is a chronic disease that needs continuous treatment. Chronic pharmacological interventions are able to decrease arterial pressure, but not cure it. An important advance on hypertension control was our recent finding that aerobic training, even not normalizing arterial pressure, sharply decreases oxidative stress and inflammation into autonornic control areas and promptly corrects baro- reflex dysfunction and cardiac vagal activity. Theses training-induced autonomic adaptations associated with reversion ofhypertrophic arteriole remodeling contribute to decrease peripheraJ vascular resistance and arterial pressure in hypertensive subjects.

Revisitando a fisiologia do sistema nervoso simpático: o que há de novo? / Facing sympathetic nervous system physiology: what's new?

o sistema nervoso autônomo (SNA), descrito no inicio do século passado, é definido como sendo o sistema de neurônios motores que inervam as glândulas e a musculatura lisa e cardíaca, sendo fundamental para a manutenção do equilibrio organismo, definindo esta situação com o termo "homeostasia", Atualmente, entretanto, reconhece-se que este sistema também apresenta neurônios sensoriais (neurônios aferentes), que transmitem as informações recebidas de receptores sensoriais autonômicos, principalmente viscerais, para o sistema nervoso central. O termo autônomo, hoje consagrado, vem da ideia de que este sistema atuava somente de forma autônoma; no entanto, hoje se admite que a atividade deste sistema é gerada, ou pelo menos supervisionada, pelo sistema nervoso central. A ativação e a desativação tônicas e reflexas de seus dois componentes, simpático e do parassimpático, determinam em condições fisiológicas ajustes do débito cardíaco e da resistência vascular periférica, contribuindo para a estabilização e manutenção da pressão arterial sistêmica durante diferentes situações fisiológicas, ampliando a capacidade de adaptação e sobrevivência do organismo. Neste contexto, o termo disautonomia se refere àquelas condições em que a função autonômica se modificou de maneira a contribuir negativamente para a saúde. Estas mudanças têm sido quantificadas e têm permitido estimar a contribuição da hiperatividade simpática na instalação e na manutenção da doença cardiovascular. Neste artigo, são revisados aspectos anatômicos e funcionais do sistema nervoso simpático e parassimpático, destacando os principais métodos de avaliação do SNA, bem como o papel da hiperatividade simpática como mecanismo desencadeador e de agravamento de disfunções cardiovasculares.

The autonomic nervous system (ANS) described at the beginning of the last century is defined as the system of motor neurons that innervate glands as well as smooth and cardiac musc/es essential for maintaining the body's balance, defining this situation with the term "homeostasis". Current1y, however it is recognized that this system also provides sensory neurons (afferent neurons) that transmit information received from sensory autonomic receptors mainly visceral to the central nervous system. The use of the term autonomic comes from the idea that this system acts only in autonomic way; however, nowadays it is accepted that the activity of this system is generated or at least supervised by the central nervous system. The tonic and reflex acti vation and deacti vation of both of its components, the sympathetic and the parasympathetic system, can determine adjustments in cardiac output and peripheral vascular resistance contributing to the stabilization and maintenance of systemic blood pressure during different physiological situations, expanding the capacity of adaptation and survival of the organismo ln this context, the terrn dysautonomia refers to those conditions in which autonomic function was changed in a way that negatively contribute to health. These changes have been quantified and have alJowed to estimate the contribution of sympathetic hyperactivity in the installation and maintenance of cardiovascular disease. In this manuscript anatomical and functional, sympathetic and parasympathetic nervous system aspects are reviewed, highJighting key evaluation methods of ANS and the role of sympathetic overacti vity as a trigger and as a worsening mechanism that can contribute to cardiovascular dysfunctions.

Claude Bernard: bicentenary of birth and his main contributions to neurology / Claude Bernard: bicentenário do nascimento e suas principais contribuições à neurologia

Claude Bernard (1813-1878) followed two main research paths: the chemical and physiological study of digestion and liver function, along with experimental section of nerves and studies on sympathetic nerves. Curare studies were, for example, of longstanding interest. His profound mental creativity and hand skillfulness, besides methodology quality, directed his experiments and findings, mainly at the Collège de France. His broader and epistemological concerns were carried out at the Sorbonne and later at the Muséum national d'Histoire naturelle. His insight gave clues to define the “ milieu intérieur”, later known as “homeostasis”, and grasp the brain complexity. Bernard followed and surpassed his master François Magendie who also fought against dogmas and laid the foundations of experimental medicine, and its main heinous tool – vivisection. Bernard created the methodological bases of experimental medicine, and collected honors as a renowned researcher.

Em suas pesquisas, Claude Bernard (1813-1878) seguiu dois caminhos principais: o estudo fisiológico e químico da digestão e da função hepática; a seção experimental de nervos e os estudos sobre nervos simpáticos. Estudos sobre curare, por exemplo, foram de interesse duradouro. Suas profundas criatividade mental e habilidade manual, além da qualidade metodológica, conduziram às suas experiências e descobertas, principalmente no Collège de France. Seus interesses sobre temas epistemológicos mais amplos foram conduzidos na Sorbonne e, posteriormente, no Muséum national d'Histoire naturelle. Seu discernimento deu subsídios para definir o “ milieu intérieur ”, mais tarde conhecido como “homeostase”, e para ajudar a compreender a complexidade do cérebro. Bernard seguiu e superou seu mestre François Magendie. Este também lutou contra dogmas e lançou os fundamentos da medicina experimental, utilizando sua principal ferramenta hedionda – a vivissecção. Bernard ampliou estes estudos e criou as bases metodológicas da medicina experimental, tendo colecionado honrarias como renomado pesquisador.

Sympathetic Response in Symptom Subgroups of Irritable Bowel Syndrome (IBS).

Objective: To evaluate sympathetic adrenergic function in irritable bowel syndrome (IBS) patients. Methods: Standard cardiovascular reflex tests were performed on forty patients with IBS and thirty healthy subjects. Sympathetic adrenergic function was assessed by measuring diastolic blood pressure response to hand grip test (HGT) at 4 min and cold pressor test (CPT) at 1min and also blood pressure response to head-up-tilt (HUT). Results: The change in diastolic pressure during (HGT) and (CPT) of IBS patients were not significantly different when compared to control. However, tilting resulted in less marked rise in diastolic pressure (6.14 ± 0.69 vs 12.1 ± 1.24 mmHg; p < 0.05) at 0.5 min and less rise in heart rate (6.03 ± 1.26 vs 10.35 ± 1.04 per min; p < 0.05) at 1 min in IBS patients. Conclusion: IBS patients had reduced sympathetic drive to (HUT) stress; however, subgroups of IBS had similar autonomic reaction.

Central chemoreceptors and neural mechanisms of cardiorespiratory control

The arterial partial pressure (P CO2) of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO2 causes an aversive awareness in conscious animals, activating wake-promoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO2-induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.

Remodeling in the ischemic heart: the stepwise progression for heart

Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI) has decreased in the last decades. However, the incidence of heart failure (HF) in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

Efeito agudo da intensidade do exercício de força na modulação autonômica cardíaca pós-exercício / Acute effect of resistance exercise intensity in cardiac autonomic modulation after exercise / Efecto agudo de intensidad del ejercicio de fuerza en la modulación autónoma del corazón post-ejercicio

FUNDAMENTO: O balanço simpatovagal cardíaco se altera após o exercício de força. Contudo, o impacto das características do treinamento de força nessa resposta ainda não está claro. OBJETIVO: Analisar o efeito agudo da intensidade do exercício de força para tronco e membros superiores na modulação autonômica cardíaca pós-exercício. MÉTODOS: Quinze homens jovens realizaram três sessões experimentais em ordem aleatória: controle (C), exercício de força com 50 por cento de 1-RM (E50 por cento) e exercício de força com 70 por cento de 1-RM (E70 por cento). As sessões incluíram 05 exercícios para tronco e membro superior, realizados em três séries de 12, 9 e 6 repetições, respectivamente. Antes e aos 20 e 50 minutos após as intervenções, a frequência cardíaca foi medida para posterior análise espectral da sua variabilidade. RESULTADOS: Em comparação aos valores anteriores à intervenção, o intervalo RR e a banda de alta frequência (AF) aumentaram (maiores alterações: + 112 ± 83 ms; +10 ± 11 un, respectivamente, p < 0,01), enquanto que a banda de baixa frequência (BF) e a razão BF/AF diminuíram (maiores alterações: -10 ± 11 un; -2 ± 2, respectivamente, p < 0,01) após a sessão C. Nenhuma dessas variáveis se alterou significantemente após a sessão E50 por cento (p > 0,05). Em comparação aos valores pré-exercício, o intervalo RR e a banda AF diminuíram (maiores alterações: -69 ± 105 ms; -13 ± 14 un, respectivamente, p < 0,01), enquanto que a banda BF e a razão BF/AF aumentaram (maiores alterações: -13 ± 14 un, +13 ± 14 un e +3 ± 3 un, respectivamente, p < 0,01) após a E70 por cento. CONCLUSÃO: A maior intensidade de exercício de força para tronco e membros superiores promoveu, agudamente, maior aumento do balanço simpatovagal cardíaco pós-exercício.

BACKGROUND: Cardiac sympathovagal balance is altered after resistance exercise. However, the impact of the characteristics of resistance training in this response remains unclear. OBJECTIVE: Analyze the acute effect of resistance exercise intensity for trunk and upper limbs in cardiac autonomic modulation after exercise. METHODS: Fifteen young men performed three experimental sessions in random order: control (C), resistance exercise with 50 percent of 1-RM (E50 percent) and resistance exercise with 70 percent of 1-RM (E70 percent). The sessions included 05 exercises for the trunk and upper limbs performed in three sets of 12, 9 and 6 repetitions, respectively. Before and at 20 and 50 minutes after the interventions, the heart rate was measured for spectral analysis of variability. RESULTS: In comparison to the values before the intervention, the RR interval and the band of high frequency (HF) increased (major changes: + 112 ± 83 ms; +10 ± 11 un, respectively, p < 0.01), while the low frequency band (LF) and LF/HF ratio decreased (major changes: -10 ± 11 pc; -2 ± 2, respectively, p < 0.01) after the session C. None of these variables changed significantly after the E50 percent session (p > 0.05). Compared to pre-exercise values, the RR interval and the HF band decreased (major changes: -69 ± 105 ms; -13 ± 14 un, respectively, p <0.01), while the LF band and the LF/HF ratio increased (major changes: -13 ± 14 un, 13 ± 3 14 ± 3 and un, respectively, p <0.01) after E70 percent. CONCLUSION: The higher intensity of resistance exercise for trunk and upper limbs promoted, in an acute manner, greater increase in cardiac sympathovagal balance after exercise.

FUNDAMENTO: El balance simpatovogal cardíaco se altera después del ejercicio de fuerza. Sin embargo, el impacto de las características del entrenamiento de fuerza en esta respuesta no está claro. OBJETIVO: Analizar el efecto agudo de intensidad del ejercicio de fuerza para el tronco y miembros en la modulación autonómica del corazón post-ejercicio. MÉTODOS: Quince hombres jóvenes realizaron tres sesiones experimentales en orden aleatorio: control (C), ejercicio de fuerza con el 50 por ciento de 1-RM (E50 por ciento) y ejercicio de fuerza con el 70 por ciento de 1-RM (E70 por ciento). Las sesiones incluyeron 05 ejercicios para tronco y miembro superior, realizados en tres series de 12, 9 y 6 repeticiones, respectivamente. Antes y a los 20 y 50 minutos después de las intervenciones, la frecuencia cardiaca se midió para un análisis espectral posterior de su variabilidad. RESULTADOS: En comparación con los valores anteriores de la intervención, el intervalo RR y la banda de alta frecuencia (AF) se incrementó (cambios importantes: + 112 ± 83 ms; +10 ± 11 un, respectivamente, p < 0,01), mientras que la banda de baja frecuencia (BF) y la razón BF/AF disminuyeron (cambios importantes: -10 ± 11 un; -2 ± 2, respectivamente, p < 0,01) tras la sesión C. Ninguna de estas variables se alteró significantemente tras la sesión E50 por ciento (p > 0,05). En comparación a los valores pre ejercicio, el intervalo RR y la banda AF disminuyeron (cambios importantes: -69 ± 105 ms; -13 ± 14 un, respectivamente, p < 0,01), mientras que la banda BF y la razón BF/AF aumentaron (cambios importantes: -13 ± 14 un, +13 ± 14 un y +3 ± 3 un, respectivamente, p < 0,01) tras la E70 por ciento. CONCLUSIÓN: La mayor intensidad de ejercicio de fuerza para el tronco y miembros superiores produjo de modo agudo, un mayor incremento simpatovagal cardíaco post-ejercicio.

Comportamento dos quimiorreflexos central e periférico na insuficiência cardíaca / Behavior of central and peripheral chemoreflexes in heart failure / Comportamiento de los quimiorreflejos central y periférico en la insuficiencia cardíaca

A síndrome da insuficiência cardíaca (IC) pode ser definida como via final de qualquer forma de doença cardíaca. Os reflexos cardiovasculares simpatoinibitórios como o reflexo arterial barorreceptor estão significativamente suprimidos na IC. Pacientes com IC apresentam maior ventilação para determinada carga de trabalho quando comparados a indivíduos normais. Esse fato gera baixa eficiência ventilatória e relaciona-se com maior ventilação relativa à produção de gás carbônico, que é um preditor de mau prognóstico, além de ser um fator limitante ao exercício. Há evidências de que o desequilíbrio autonômico contribua para a patogênese e a progressão da insuficiência cardíaca. Os quimiorreflexos são os principais mecanismos de controle e regulação das respostas ventilatórias às mudanças de concentração do oxigênio e gás carbônico arterial. A ativação do quimiorreflexo causa aumento da atividade simpática, frequência cardíaca, pressão arterial e volume minuto. No entanto, o aumento do volume minuto e da pressão arterial, pelo feedback negativo provocam inibição da resposta simpática à ativação do quimiorreflexo. Apesar das alterações funcionais dos reflexos, seu comportamento em condições normais e patológicas, especialmente sua contribuição para o estado simpatoexcitatório encontrado na IC, não tem sido amplamente estudado. Dessa forma, esta revisão tem por objetivo integrar os conhecimentos a respeito dos quimiorreflexos central e periférico na síndrome da insuficiência cardíaca, bem como esclarecer a influência da terapêutica medicamentosa da insuficiência cardíaca nos quimiorreflexos.

The heart failure (HF) syndrome can be defined as the final pathway of any type of heart disease. The sympatho-inhibitory cardiovascular reflexes, such as the arterial baroreceptor reflex, are significantly decreased in HF. Patients with HF present higher ventilation for a certain workload when compared with normal individuals. This fact generates low ventilatory efficiency and is related to higher ventilation associated with the carbon dioxide production, which is a predictor of bad prognosis, in addition to being a limiting factor for the practice of exercises. There is evidence that the autonomic imbalance contributes to the pathogenesis and the progression of heart failure. The chemoreflexes are the main mechanisms of control and regulation of the ventilatory responses to the changes in concentrations of arterial oxygen and carbon dioxide. The chemoreflex activation causes an increase in the sympathetic activity, heart rate, arterial pressure and minute volume. However, the increase in the minute volume and the arterial pressure, due to negative feedback, cause inhibition of the sympathetic response at the chemoreflex activation. In spite of the functional alterations of the reflexes, their behavior in normal and pathological conditions, especially their contribution to the sympathoexcitatory state observed in HF has not been broadly studied. Therefore, this review aims at integrating the knowledge on central and peripheral chemoreflexes in HF syndrome, as well as clarifying the influence of the heart failure drug therapy on the chemoreflexes.

El síndrome de insuficiencia cardíaca (IC) puede ser definido como vía final de cualquier forma de enfermedad cardíaca. Los reflejos cardiovasculares simpáticoinhibitorios como el reflejo arterial barorreceptor están significativamente suprimidos en la IC. Pacientes con IC presentan mayor ventilación para determinada carga de trabajo cuando son comparados a individuos normales. Ese hecho genera baja eficiencia ventilatoria y se relaciona con mayor ventilación relativa a la producción de gas carbónico, que es un predictor de mal pronóstico, además de ser un factor limitante del ejercicio. Hay evidencias de que el desequilibrio autonómico contribuya a la patogénesis y la progresión de la insuficiencia cardíaca. Los quimiorreflejos son los principales mecanismos de control y regulación de las respuestas ventilatorias a los cambios de concentración del oxígeno y gas carbónico arterial. La activación del quimiorreflejo causa aumento de la actividad simpática, frecuencia cardíaca, presión arterial y volumen minuto. Mientras tanto, el aumento del volumen minuto y de la presión arterial, por el feedback negativo provocan inhibición de la respuesta simpática a la activación del quimiorreflejo. A pesar de las alteraciones funcionales de los reflejos, su comportamiento en condiciones normales y patológicas, especialmente su contribución al estado simpáticoexcitatorio encontrado en la IC, no ha sido ampliamente estudiado. De esa forma, esta revisión tiene por objetivo integrar los conocimientos respecto a los quimiorreflejos central y periférico en el síndrome de insuficiencia cardíaca, así como aclarar la influencia de la terapéutica medicamentosa de la insuficiencia cardíaca en los quimiorreflejos.

Ovariectomy does not affect the cardiac sympathovagal balance of female SHR but estradiol does

The low incidence of cardiovascular diseases, including hypertension, in premenopausal women has led to the conclusion that ovarian hormones may have a protective effect on the cardiovascular system. We evaluated the effects of ovariectomy and/or estradiol on sympathovagal balance and heart rate variability (HRV) in female spontaneously hypertensive rats (SHR) with tachycardia and compared them to Wistar rats (12 weeks old; N = 8-12). Ovariectomy (OVX) and/or estradiol (10 µg/kg) did not affect basal arterial pressure in either rat strain, but estradiol increased basal heart rate (HR) in OVX SHR (454 ± 18 vs 377 ± 9 bpm). HR changes elicited by methylatropine and propranolol were used to evaluate the sympathovagal balance. Ovariectomy did not affect the cardiac sympathovagal balance of any group, while estradiol increased sympathetic tone in OVX SHR (120 ± 8 vs 56 ± 10 bpm) and sham-operated Wistar rats (57 ± 7 vs 28 ± 4 bpm), and decreased the parasympathetic tone only in OVX SHR (26 ± 7 vs 37 ± 5 bpm). HRV was studied in the frequency domain (Fast Fourier Transformation). Spectra of HR series were examined at low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz) bands. The power of LF, as well as the LF/HF ratio, was not affected by ovariectomy, but estradiol increased both LF (29 ± 4 vs 18 ± 3 nu in Wistar sham-operated, 26 ± 5 vs 15 ± 3 nu in Wistar OVX, 50 ± 3 vs 38 ± 4 nu in SHR sham-operated, and 51 ± 3 vs 42 ± 3 nu in SHR OVX) and LF/HF (0.48 ± 0.08 vs 0.23 ± 0.03 nu in Wistar sham-operated, 0.41 ± 0.14 vs 0.19 ± 0.05 nu in Wistar OVX, 0.98 ± 0.11 vs 0.63 ± 0.11 nu in SHR sham-operated, and 1.10 ± 0.11 vs 0.78 ± 0.1 nu in SHR OVX). Thus, we suggest that ovariectomy did not affect the cardiac sympathovagal balance of SHR or Wistar rats, while estradiol increased the sympathetic modulation of HR.

Taser technology: medical, legal, ethical & social implications of introduction of taser gun in India.

A person struck by a taser gun experiences stimulation of his sensory and motor nerves, resulting in strong involuntary muscle contractions. This may lead to physiological changes similar to a moderate intensity exercise. The mechanism of action of Taser gun is Electro-Muscular Disruption (EMD) technology. Though Tasers are considerably safe, some incidents of injury and deaths have been reported. The primary cause of such deaths is found to be influenced by some underlying pathology or some external factor, rather than Taser itself. Recent introduction Taser gun as weapon in Indian police has raised various medico legal, social and ethical issues regarding the safety of using taser guns. In this article we have reviewed all the medical, Legal, Ethical and Social aspects of introduction of taser gun in India as weapon. It has been concluded that Taser is a proportionate, low risk weapon can be used to resolving incidents where the public or officers face severe violence or the threat of such violence which cannot safely be dealt with by other means.

Schwannoma in Head and Neck: Preoperative Imaging Study and Intracapsular Enucleation for Functional Nerve Preservation

PURPOSE: In treating schwannoma patients, it is critical to determine the origin of the tumor to preserve nerve function. We evaluated the validity of preoperative imaging studies in distinguishing the neurological origin of the schwannomas of the head and neck, and the efficacy of intracapsular enucleation in preserving nerve function. MATERIALS AND METHODS: In 7 cases of schwannomas in the head and neck region, we predicted whether the tumor originated from the vagus nerve or the cervical sympathetic chain through imaging studies including computed tomography (CT) and magnetic resonance imaging (MRI). All patients were performed intracapsular enucleation, and the function of the vagus nerve and the sympathetic nerve was evaluated preoperatively and postoperatively. RESULTS: Preoperative imaging studies showed 6 cases where the tumor was located between the carotid artery and the internal jugular vein, and 1 case where the tumor was located posteriorly, displacing the carotid artery and the internal jugular vein anteriorly. At the time of operation, we confirmed schwannoma originating from the vagus nerve on the first 6 cases, and schwannoma originating from the sympathetic nervous system on the last case. All patients went through successful intracapsular enucleation, and of the seven schwannoma cases, 6 patients maintained normal postoperative neurological function (85.7%). CONCLUSION: Preoperative imaging studies offer valuable information regarding the location and origination of the tumor, and intracapsular enucleation helped us to preserve the nerve function.

Receptores de la serotonina que inhiben el tono simpático vasopresor en la rata descerebrada y desmedulada / Role of serotonin receptors in vascular tone in the pithed rat

Serotonin (5-hydroxytryptamine; 5-HT) has been shown to produce vascular sympatho-inhibition in a wide variety of isolated blood vessels by activation of prejunctional 5-HT1 receptors. After considering the mechanisms involved in modulating neuroeffector transmission, the present review analyzes the experimental findings identifying the pharmacological profile of the 5-HT receptors that inhibit the sympathetically-induced vasopressor responses in pithed rats. Thus, 5-HT-induced sympatho-inhibition has been shown to be: (i) unaffected by physiological saline or by the selective antagonists ritanserin (5-HT2), MDL72222 (5-HT3) or tropisetron (5-HT3/4); (ii) blocked by methysergide, a non-selective 5-HT1/2 receptor antagonist; and (iii) potently mimicked by 5-carboxamidotryptamine (5-CT), a non-selective 5-HT1 receptor agonist, as well as by the selective agonists 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP93,129 (5-HT1B), and sumatriptan (5-HT1B/1D). These findings show the involvement of prejunctional 5-HT1 receptors. With the use of selective antagonists, it has been shown subsequently that the sympatho-inhibition induced by indorenate, CP93, 129, and sumatriptan was selectively antagonized by WAY100635 (5-HT1A), cyanopindolol (5-HT1A/1B), and GR127935 (5-HT1B/1D), respectively. These results demonstrate that the 5-HT1 receptors mediating sympatho-inhibition on the systemic vasculature of pithed rats resemble the pharmacological profile of the 5-HT1A, 5-HT1B, and 5-HT1D subtypes.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

Numerosas formas de evidência experimental obtidas nos últimos 37 anos demonstraram inequivocamente que a medula oblongata contém os principais circuitos responsáveis pela geração e manutenção do tono vasomotor e a regulação da pressão arterial. A visão atual que possuímos destes circuitos deriva em grande parte dos estudos de Pedro Guertzenstein, um estudante e mais tarde Professor de Fisiologia da UNIFESP e seus colaboradores. Nesta revisão nós sumarizamos os seus principais resultados assim como a nossa colaboração para uma melhor compreensão da regulação da pressão arterial em condições normais e patológicas.

A brief review of chronic exercise intervention to prevent autonomic nervous system changes during the aging process: [review]

The aging process is associated with alterations in the cardiovascular and autonomic nervous systems. Autonomic changes related to aging involve parasympathetic and sympathetic alterations leading to a higher incidence of cardiovascular disease morbidity and mortality. Several studies have suggested that physical exercise is effective in preventing deleterious changes. Chronic exercise in geriatrics seems to be associated with improvement in the cardiovascular system and seems to promote a healthy lifestyle. In this review, we address the major effects of aging on the autonomic nervous system in the context of cardiovascular control. We examine the use of chronic exercise to prevent cardiovascular changes during the aging process.

Role of the caudal pressor area in the regulation of sympathetic vasomotor tone

It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the ventrolateral medulla were initially identified: the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the RVLM raises arterial blood pressure and sympathetic nerve activity, and activation of the CVLM causes opposite effects. The RVLM premotor neurons project directly to sympathetic preganglionic neurons and are involved in the maintenance of resting sympathetic vasomotor tone. A significant proportion of tonic activity in the RVLM sympathetic premotor neurons is driven by neurons located in a third region of the ventrolateral medulla denominated caudal pressor area (CPA). The CPA is a pressor region located at the extreme caudal part of the ventrolateral medulla that appears to have an important role controlling the activity of RVLM neurons. In this brief review, we will address the importance of the ventrolateral medulla neurons for the generation of resting sympathetic tone related to arterial blood pressure control focusing on two regions, the RVLM and the CPA.