Fisiología respiratoria: el control de la respiración / Respiratory fisiology: the breath control

El control de la respiración comprende un componente automático involuntario y un componente voluntario, con centros de control en el tronco encefálico, principalmente en la médula oblonga y en el puente, y en la corteza cerebral. Estos centros reciben aferencias provenientes de sensores que detectan señales químicas y no químicas, interactúan entre sí y generan respuestas que llegan a las neuronas motoras inferiores a nivel de médula espinal. Estos procesos determinan el funcionamiento de los músculos implicados en la respiración, y de ese modo permite garantizar que los niveles de pO2 p CO2 y pH en la sangre arterial se mantengan en forma óptima, frente a diferentes situaciones y demandas metabólicas. Se hace una revisión actualizada del tema que permita comprender estos procesos.

The control of breathing comprises an involuntary automatic component and a voluntary component, with control centers in the brain stem, mainly in the medulla oblongata and in the bridge, and in the cerebral cortex. These centers receive afferences from sensors that detect chemical and non-chemical signals, interact with each other and generate responses that reach the lower motor neurons at the spinal cord level. These processes determine the functioning of the muscles involved in breathing, and thus ensure that the levels of pO2 p CO2 and pH in arterial blood are optimally maintained, in the face of different situations and metabolic demands. An up-to-date review of the subject is carried out to understand these processes.

Hemodynamic and ventilatory response to different levels of hypoxia and hypercapnia in carotid body-denervated rats

OBJECTIVE: Chemoreceptors play an important role in the autonomic modulation of circulatory and ventilatory responses to changes in arterial O2 and/or CO2. However, studies evaluating hemodynamic responses to hypoxia and hypercapnia in rats have shown inconsistent results. Our aim was to evaluate hemodynamic and respiratory responses to different levels of hypoxia and hypercapnia in conscious intact or carotid body-denervated rats. METHODS: Male Wistar rats were submitted to bilateral ligature of carotid body arteries (or sham-operation) and received catheters into the left femoral artery and vein. After two days, each animal was placed into a plethysmographic chamber and, after baseline measurements of respiratory parameters and arterial pressure, each animal was subjected to three levels of hypoxia (15, 10 and 6% O2) and hypercapnia (10% CO2). RESULTS: The results indicated that 15% O2 decreased the mean arterial pressure and increased the heart rate (HR) in both intact (n = 8) and carotid body-denervated (n = 7) rats. In contrast, 10% O2did not change the mean arterial pressure but still increased the HR in intact rats, and it decreased the mean arterial pressure and increased the heart rate in carotid body-denervated rats. Furthermore, 6% O2 increased the mean arterial pressure and decreased the HR in intact rats, but it decreased the mean arterial pressure and did not change the HR in carotid body-denervated rats. The 3 levels of hypoxia increased pulmonary ventilation in both groups, with attenuated responses in carotid body-denervated rats. Hypercapnia with 10% CO2 increased the mean arterial pressure and decreased HR similarly in both groups. Hypercapnia also increased pulmonary ventilation in both groups to the same extent. CONCLUSION: This study demonstrates that the hemodynamic and ventilatory responses varied according to the level of hypoxia. Nevertheless, the hemodynamic and ventilatory responses to hypercapnia did not depend on the activation of the peripheral carotid chemoreceptors.

Influência da desnervação seletiva dos barorreceptores e quimiorreceptores nas variáveis hemodinâmicas e morfofuncionais dos tecidos cardíaco e músculo-esquelético em ratos espontaneamante hipertensos / Influence of selective denervation of baroreceptors and chemoreceptors in hemodynamic variables and tissue morphofunctional cardiac and musculoskeletal in spontaneously hypertensive rats

A hipertensão arterial (HA) é uma doença multifatorial na qual há a interação de vários mecanismos, e está relacionada com alterações funcionais e/ou estruturais dos órgãos-alvo. Alterações funcionais dos mecanismos regulatórios da pressão arterial (PA) a curto prazo, como os barorreceptores e os quimiorreceptores, vem sendo bastante exploradas com o objetivo de entender os possíveis mecanismos que podem estar relacionadas à gênese da HA. Diante disso, utilizamos o modelo experimental de desnervação sinoaórtica (DSA) e desnervação seletiva desses aferentes (aórtica DA) e/ou carotídea (DC) e a ligadura da artéria do corpúsculo carotídeo (LA) para avaliarmos a importância relativa dos barorreceptores e quimioreceptores no controle neurogênico da circulação mediando respostas cardíacas e músculo-esqueléticas na HA. Para tanto, utilizamos ratos Wistar (CTR) e espontaneamente hipertensos (SHR) submetidos às diferentes desnervações (SHRDSA/ SHRDA / SHRDC), bem como, a ligadura da artéria do corpúsculo carotídeo (SHRLA). Os animais foram acompanhados durante 10 semanas após as desnervações seletivas, e em seguida foram realizadas as avaliações ecocardiográficas, gasometria arterial, hemodinâmicas, autonômicas e de fluxo sanguíneo regional. Posteriormente, os animais foram eutanasiados para a coleta dos tecidos para as avaliações gênicas e histológicas. Resultados: Os animais SHR apresentaram disfunções hemodinâmicas, autonômicas e gasométricas (alcalose respiratória) quando comparado ao grupo CTR, assim como nas análises de hipertrofia, fluxo e histologia do músculo esquelético, como transição no fenótipo para um perfil mais glicolítico no sóleo e aumento da área de secção transversa das fibras do tipo I e redução das fibras do tipo IIB no músculo diafragma. Nos grupos experimentais hipertensos, os animais com prejuízo do quimiorreflexo (SHRDC, SHRLA e SHRDSA), apresentaram valores maiores de pCO2 em relação ao grupo SHR e SHRDA...

Arterial hypertension (AH) is a multifactorial disease on which there is the interaction of several mechanisms , therefore is related to functional and / or structural changes of the target organ . Functional changes of the regulatory mechanisms of blood pressure (BP) in the short term , as pressoreceptor and chemoreceptors, has been extensively explored in order to understand the possible mechanisms that may be related to the genesis of hypertension. Thus, we used the experimental model of sinoaortic denervation (DSA) and selective denervation of those afferent aortic (DA) and / or carotid (DC) and the ligature of the carotid body artery (LA) to evaluate the relative importance of baroreceptors and chemoreceptors on control of neurogenic circulation mediating cardiac and musculoskeletal responses in HA. There by, we used Wistar rats (CTR) and spontaneously hypertensive rats (SHR) subjected to different denervation (SHRDSA / SHRDA / SHRDC) and the ligature of the carotid body artery (SHRLA). The animals were followed for 10 weeks after the selective denervation it was performed echocardiographic evaluations, blood gas, hemodynamic, autonomic and regional blood flow. Subsequently, the animals were euthanized for tissue collection for genetic and histological evaluations. Results: SHR animals showed hemodynamic, autonomic dysfunction and gas exchange (respiratory alkalosis) compared to CTR group as well as the analysis of hypertrophy, flow and histology of skeletal muscle, such as the transition to a more glycolytic phenotype profile in soleus and increased cross-sectional area of type I fibers and reduction of type IIB fibers in the diaphragm . In hypertensive experimental groups, animals with prejudice chemoreflex (SHRDC, SHRLA and SHRDSA) , showed higher pCO2 compared to SHR and SHRDA group. All groups with different denervation showed autonomic changes in blood flow and capillarization. However, our major findings were compared to SHRDA group...

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.

Comportamento do ergorreflexo na insuficiência cardíaca / Ergoreflex activity in heart failure / Comportamiento del ergorreflejo en la insuficiencia cardiaca

Grande número de evidências tem sugerido a existência de uma rede de reflexos que se tornam hiperativos secundariamente a alterações músculo-esqueléticas que ocorrem na síndrome insuficiência cardíaca (IC). Estes, aliados aos reflexos cardiovasculares simpato-inibitórios, suprimidos na síndrome, podem contribuir para a intolerância ao exercício físico. A hiperativação dos sinais originados dos receptores localizados nos músculos esqueléticos (mecanoceptores - metaborreceptores) é uma hipótese proposta recentemente para explicar a origem dos sintomas de fadiga e dispneia e os efeitos benéficos do treinamento físico na síndrome da IC. Na IC, outras alterações nos sistemas de controle reflexo, que não são mutuamente exclusivos, contribuem para dispneia. Estimulação inapropriada dos barorreceptores arteriais com consequente falta de inibição da descarga do metaborreflexo muscular e quimiorreflexo carotídeo e aumento da vasoconstricção renal com liberação de angiotensina II pode também ser considerada. Apesar das alterações funcionais dos reflexos terem sido usadas de maneira independente para ilustrar a excitação simpática observada na IC, a interação entre esses reflexos em condições normais e patológicas, especialmente sua contribuição para o estado simpato-excitatório encontrado na IC, não tem sido amplamente estudados. Assim, o problema se ambos os receptores musculares (mecano e metaborreceptores) estão envolvidos na gênese da exacerbação do ergorreflexo observado na IC ainda fica a ser resolvido. Dessa forma, essa revisão tem por objetivo integrar os conhecimentos a respeito do mecano e metaborreflexo (ergorreflexo) na síndrome da insuficiência cardíaca bem como esclarecer a influência da terapêutica medicamentosa da IC no ergorreflexo.

A large body of evidence has suggested the existence of a reflex network that becomes hyperactive secondary to musculoskeletal alterations that occur in heart failure (HF) syndrome. Together with sympathoinhibitory cardiovascular reflexes, suppressed in the presence of the syndrome, heart failure can contribute to physical exercise intolerance. The hyperactivation of signals originated from receptors located in skeletal muscles (mechanoreceptors - metaboreceptors) is a recently proposed hypothesis to explain the origin of fatigue and dyspnea symptoms in HF. In HF, other alterations in the reflex control system, which are not mutually exclusive, contribute to dyspnea. The inappropriate stimulation of the arterial baroreceptors, with the consequent lack of inhibition of the muscle metaboreflex and carotid chemoreflex unloading and the increase in the renal vasoconstriction with angiotensin II release can also be considered. Although the functional alterations of the reflexes were used independently to illustrate the sympathetic excitation observed in HF, the interaction between these reflexes under normal and pathological conditions, especially its contribution to the sympathoexcitatory state found in HF, has not been broadly investigated. Therefore, questions about a possible association between the muscle receptors (mechano and metaboreceptors) in the genesis of the ergoreflex exacerbation, observed in HF, remain. Thus, the objective of this review was to integrate the knowledge on the mechano and metaboreflex (ergoreflex) in HF syndrome, as well as to clarify the influence of HF drug therapy on the ergoreflex.

Gran número de evidencias viene sugerido la existencia de una red de reflejos que se hacen hiperactivos secundariamente a alteraciones musculoesqueléticas que se producen en el síndrome de la insuficiencia cardiaca (IC). Aliada a los reflejos cardiovasculares simpatoinhibitorios, suprimidos en el síndrome, la insuficiencia cardiaca puede contribuir a la intolerancia al ejercicio físico. La hiperactivación de los señales originados de los receptores ubicados en los músculos esqueléticos (mecanorreceptores - metaborreceptores) es una hipótesis propuesta recientemente para explicar el origen de los síntomas de fatiga y disnea y de los efectos benéficos del entrenamiento físico en el síndrome de IC. En la IC, otras alteraciones en los sistemas de control reflejo, que no son mutuamente exclusivos, contribuyen a la disnea. Estimulación inapropiada de los barorreceptores arteriales, con consecuente falta de inhibición de la descarga del metaborreflejo muscular y quimiorreflejo carotídeo, y el aumento de la vasoconstricción renal con liberación de angiotensina II se pueden también tener en cuenta. A pesar de las alteraciones funcionales de los reflejos haber sido utilizadas de manera independiente para ilustrar la excitación simpática observada en la IC, la interacción entre estos reflejos en condiciones normales y patológicas, especialmente su contribución para el estado simpatoexcitatorio encontrado en la IC, no viene siendo ampliamente estudiada. De este modo, resta todavía un cuestionamiento sobre la posible relación entre los receptores musculares (mecano y metaborreceptores) en la génesis de la exacerbación del ergorreflejo observado en la IC. Por tanto, esta revisión tiene por objetivo integrar los conocimientos respecto al mecano y metaborreflejo (ergorreflejo) en el síndrome de la insuficiencia cardiaca, así como aclarar la influencia de la terapéutica medicamentosa de la IC en el ergorreflejo.

Behavioural responses to human skin extracts and antennal phenotypes of sylvatic first filial generation and long rearing laboratory colony Rhodnius prolixus

Chagas disease is a major public health issue and is mainly spread by Triatominae insects (Hemiptera: Reduviidae). Rhodnius prolixus is the main vector species in Northern South America. Host-seeking behaviour in R. prolixus is mediated by different compounds that are produced by and emanate from the host or microbiota on the host's skin. We tested the behavioural responses of sylvatic first filial generation (F1) and colony insects to extracts of human skin with a dual choice olfactometer. In addition, we compared the antennal phenotypes in both populations. No statistical differences were found between the two populations at the behavioural level. Both showed a preference for face and feet extracts and this effect was abolished for face extracts after treatment with an antibacterial gel. The observation of the antennal phenotype showed that there were differences between both groups in the total length, total surface area and number and density of bristles. However, the number and density of chemoreceptive sensilla (basiconic and thin and thick-walled trichoids) and the total density of sensilla did not show statistically significant differences. These results demonstrate that colony insects, which have only been fed with living hens for the last 30 years, are attracted by human skin extracts in a similar way as F1 sylvatic insects.

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.

Quimiossensibilidade durante exercício na insuficiência cardíaca: respostas ventilatórias, cronotrópicas e neurohormonais / Exercise chemosensitivity in heart failure: ventilatory, chronotropic and neurohormonal responses / Quimiosensibilidad durante ejercicio en la insuficiencia cardíaca: respuestas ventilatorias, cronotrópicas y neurohormonales

FUNDAMENTO: Insuficiência cardíaca (IC) está associada com aumento da quimio-sensibilidade periférica e central em repouso, que pode estar correlacionada com um aumento na resposta ventilatória durante exercício. Entretanto, SUS sensibilidade na IC durante o exercício ainda não foi reportada. OBJETIVO: Testar se o estímulo dos quimiorreceptores centrais e periféricos em pacientes com IC pode modular respostas ventilatórias, cronotrópicas e neurohormonais durante exercício submáximo. MÉTODOS: Investigamos a quimio-sensibilidade central e periférica em 15 pacientes com insuficiência cardíaca (IC) e 7 controles normais (C), comparando a resposta durante 3 testes de caminhada de 6 minutos (TC6M), realizado em esteira ergométrica com: ar ambiente, em hipóxia e em hipercapnia (em ordem randômica). RESULTADOS: FR em ar ambiente nos grupos C e IC foi 17±2 e 22±2 (p<,0001); em hipóxia, foi 17±1 e 23±2 (p<,02); com CO25 por cento foi 20±2 e 22±5 (p<,02). Volume tidal (VT) ou corrente em ar ambiente foi 1,25±0,17 e 1,08±0,19 (p<,01); em hipóxia 1,65±0,34 e 1,2±0,2(p<,0001); com CO25 por cento 1,55±0,46 e 1,29±0,39 (p<,0001). Em repouso, o aumento na IC foi maior para VE (C 33±40 por cento, IC 62±94 por cento, p<,01), FC(C 7±10 por cento, IC 10±10 por cento, p<0,05) em repouso. Durante a hipóxia, o aumento durante o exercício na IC foi maior para FR (C 1±4, IC 11±6,p<,05), FC (C 12±2, IC 14±3, p<,05), VE/VO2 (C -4±18 por cento, IC 24±21 por cento, p<,01), FC/VO2 (C -26±11 por cento, IC 11±5 por cento, p<,01), VE/DC (C 36±10 por cento, 46±14, p<,05 por cento ) and FC/DC (C 18±8 por cento, HF 29±11, p<,01). Durante exercício em hipóxia no grupo IC, o NO diminuiu e os níveis de IL-6 e aldosterona aumentaram. Os níveis neurohormonais permaneceram inalterados no grupo C. CONCLUSÃO: A quimio-sensibilidade central e a periférica durante o exercício estão aumentadas na IC e podem modular padrões respiratórios, cronotrópicos cardíacos e atividade neurohormonal durante exercício.

BACKGROUND: Heart failure (HF) is associated with resting increased peripheral and central chemosensitivity which may correlate with an increased ventilatory response to exercise. However, its sensitivity in HF during exercise was never really reported. OBJECTIVE: We tested if stimulation of central and peripheral chemoreceptors in HF patients could modulate ventilatory, chronotropic, and neurohormonal response during submaximal exercise. METHODS: We investigated central and peripheral chemosensitivity in 15 HF and 7 control (C) comparing response through three 6 minute walking tests conducted in a treadmill with : room air, hypoxia, and hypercapnia (in a randomic order). RESULTS: RR at room air C and HF was 17±2 and 22±2 (p<.0001); at hypoxia 17±1 and 23±2 (p<.02); at CO25 percent was 20±2 and 22±5 (p<.02). Tidal volume (TV) at room air was 1.25±0.17 and 1.08±0.19 (p<.01); at hypoxia 1.65±0.34 and 1.2±0.2 (p<.0001); at CO25 percent 1.55±0.46 and 1.29±0.39 (p<.0001). At rest the increment in HF was higher for VE (C 33±40 percent, HF 62±94 percent, p<.01), HR(C 7±10 percent, HF 10±10 percent, p<0.05) at rest. During hypoxia exercise increment in HF was higher for RR (C 1±4, HF 11±6,p<.05), HR (C 12±2, HF 14±3, p<.05), VE/VO2 (C -4±18 percent, HF 24±21 percent, p<.01), HR/VO2 (C -26±11 percent, HF 11±5 percent, p<.01), VE/WD (C 36±10 percent, 46±14, p<.05 percent) and HR/WD (C 18±8 percent, HF 29±11, p<.01). During HF hypoxia exercise NO reduced, and IL-6, aldosterone levels increased. Neurohormonal levels unchanged in C. CONCLUSION: Exercise peripheral and central chemosensitivity are increased in HF and may modulate respiratory pattern, cardiac chronotropic, and neurohormonal activity during exercise.

FUNDAMENTO: La insuficiencia cardíaca (IC) está asociada con aumento de la quimiosensibilidad periférica y central en reposo, que puede estar correlacionada con un aumento en la respuesta ventilatoria durante ejercicio. Mientras tanto, SUS sensibilidad en la IC durante el ejercicio aun no fue reportada. OBJETIVO: Verificar si el estímulo de los quimiorreceptores centrales y periféricos en pacientes con IC puede modular respuestas ventilatorias, cronotrópicas y neurohormonales durante ejercicio submáximo. MÉTODOS: Investigamos la quimiosensibilidad central y periférica en 15 pacientes con insuficiencia cardíaca (IC) y 7 controles normales (C), comparando la respuesta durante 3 tests de caminata de 6 minutos (TC6M), realizado en cinta ergométrica con: aire ambiente, en hipoxia y en hipercapnia (en orden randómico). RESULTADOS: FR en aire ambiente en los grupos C y IC fue 17±2 y 22±2 (p<,0001); en hipoxia, fue 17±1 y 23±2 (p<.02); con CO25 por ciento fue 20±2 y 22±5 (p<,02). Volumen tidal (VT) o corriente en aire ambiente fue 1,25±0,17 y 1,08±0,19 (p<,01); en hipoxia 1,65±0,34 y 1,2±0,2 (p<,0001); con CO25 por ciento 1,55±0,46 y 1,29±0,39 (p<,0001). En reposo, el aumento en la IC fue mayor para VI (C 33±40 por ciento, IC 62±94 por ciento, p<,01), FC(C 7±10 por ciento, IC 10±10 por ciento, p<0,05) en reposo. Durante la hipoxia, el aumento durante el ejercicio en la IC fue mayor para FR (C 1±4, IC 11±6, p<.05), FC (C 12±2, IC 14±3, p<.05), VI/VO2 (C -4±18 por ciento, IC 24±21 por ciento, p<.01), FC/VO2 (C -26±11 por ciento, IC 11±5 por ciento, p<.01), VI/DC (C 36±10 por ciento, 46±14, p<.05 por ciento) y FC/DC (C 18±8 por ciento, HF 29±11, p<.01). Durante ejercicio en hipoxia en el grupo IC, el NO disminuyó y los niveles de IL-6 y aldosterona aumentaron. Los niveles neurohormonales permanecieron inalterados en el grupo C. CONCLUSIÓN: La quimiosensibilidad central y la periférica durante el ejercicio están aumentadas en la IC y pueden modular estándares respiratorios, cronotrópicos cardíacos y actividad neurohormonal durante ejercicio.

Control of respiration in fish, amphibians and reptiles

Fish and amphibians utilise a suction/force pump to ventilate gills or lungs, with the respiratory muscles innervated by cranial nerves, while reptiles have a thoracic, aspiratory pump innervated by spinal nerves. However, fish can recruit a hypobranchial pump for active jaw occlusion during hypoxia, using feeding muscles innervated by anterior spinal nerves. This same pump is used to ventilate the air-breathing organ in air-breathing fishes. Some reptiles retain a buccal force pump for use during hypoxia or exercise. All vertebrates have respiratory rhythm generators (RRG) located in the brainstem. In cyclostomes and possibly jawed fishes, this may comprise elements of the trigeminal nucleus, though in the latter group RRG neurons have been located in the reticular formation. In air-breathing fishes and amphibians, there may be separate RRG for gill and lung ventilation. There is some evidence for multiple RRG in reptiles. Both amphibians and reptiles show episodic breathing patterns that may be centrally generated, though they do respond to changes in oxygen supply. Fish and larval amphibians have chemoreceptors sensitive to oxygen partial pressure located on the gills. Hypoxia induces increased ventilation and a reflex bradycardia and may trigger aquatic surface respiration or air-breathing, though these latter activities also respond to behavioural cues. Adult amphibians and reptiles have peripheral chemoreceptors located on the carotid arteries and central chemoreceptors sensitive to blood carbon dioxide levels. Lung perfusion may be regulated by cardiac shunting and lung ventilation stimulates lung stretch receptors.

Los baroquimiorreceptores carotídeos: órganos blanco de la hipertensión arterial / Carotid barochemoreceptors: target organs of arterial hypertension

El cuerpo carotídeo (CC) es el principal quimiorreceptor arterial periférico, capaz de sensar los cambios en la PaO2, la PaCO2 y de pH y transducirlos en señales nerviosas reguladoras de respuestas ventilatorias, circulatorias y endócrinas, que permiten una adaptación a la hipoxemia, la acidosis y la hipercapnia. El seno carotídeo, ubicado próximo al CC, con función barorreceptora, genera respuestas cardiovasculares que descienden la tensión arterial (TA). Ambas estructuras son inervadas por el nervio del seno carotídeo (NSC), que a su vez se proyecta al núcleo del tracto solitario (NTS), y se relacionan íntimamente entre sí y reciben la denominación de baroquimiorreceptores. Últimamente estos órganos se han considerado claves en la regulación de respuestas cardiorrespiratorias homeostáticas que podrían estar íntimamente relacionadas con el desarrollo y el mantenimiento de la hipertensión arterial (HTA). Existe escasa información sobre los cambios estructurales que ocurren en estos órganos durante la HTA y/o como consecuencia de ella. Nuestro planteo es que los baroquimiorreceptores carotídeos representarían un nuevo “órgano blanco” de la HTA. En diversos estudios realizados en seres humanos y en modelos de hipertensión sistólica en animales observamos un daño severo en el CC que se correlacionó significativamente con la elevación de la TA. A su vez, considerando que el sistema renina-angiotensina-aldosterona (SRAA) tendría un papel significativo en la fisiopatología del daño observado, demostramos que el ramipril, versus el atenolol, ejerce un efecto protector sobre el CC más allá de la mera reducción de la TA. Incluso el losartán mostró dicho efecto protector, aun cuando los animales utilizados en los modelos fueron normotensos. Nuestros hallazgos indican que el CC se comporta como un órgano blanco de la HTA y que la activación de un SRAA local sería responsable de los cambios morfológicos y funcionales observados.

The carotid body (CB) is the main peripheral arterial chemoreceptor, able to sense changes in PaO2, PaCO2 and pH, and translate them into nervous signals that regulate ventilating, circulating and endocrine responses which allow adaptation to hypoxemia, acidosis, and hypercapnia. The carotid sinus, located next to the CB, with a baroreceptor function, generates cardiovascular responses that decrease arterial hypertension. Both structures are innervated by the carotid sinus nerve (CSN), which is projected to the solitary tract nucleus (STN), closely inter-related and called barochemoreceptors. Lately, these organs have been considered key in the regulation of homeostatic cardiorespiratory responses that could be intimately related to the development and maintenance of arterial hypertension (AHT). There is scant information on the structural changes that occur in these organs during AHT and/or as its consequence. Our hypothesis is that carotid barochemoreceptors would be a new “target organ” of the AHT. In several studies performed in humans and in models of systolic hypertension in animals we observed a severe damage in the CB which was significantly correlated with elevation of the AT. Hence, considering that the renin-angiotensin-aldosterone system(RAAS) would play a significant role in the pathophysiology of the observed injury, we showed that ramipril versus atenolol has a protective effect on the CB further to the mere decrease of the AT. Even though the animal models used had normal pressure, losartan showed this protective effect. Our findings indicate that the CB behaves as a target organ in AHT and the activation of a local RAAS would be responsible for the morphological and functional changes that were observed.

Controle da pressäo arterial / Blood pressure control

A manutenção dos níveis normais da pressão arterial é condição necessária para perfusão sanguínea tecidual adequada. A hipertensão é uma disfunsão dos mecanismos controladores da pressão arterial, que pode culminar com a falência do organismo. O controle da pressão arterial é feito por mecanismos diversos, de natureza neural ou hormonal, O controle neural é feito por meio de eferências do sistema nervoso autônomo, atuando sobre o coração e os vasos. No coração, modulam o débito cardíaco por meio do enchimento dos ventrículos e da atividade inotrópica e cronotrópica; nos vasos, atuam sobre a resistência periférica. Os principais mecanismos reflexos que atuam na regulação da pressão arterial são o barorreflexo, os reflexos cardiopulmonares, o quimiorreflexo e o reflexo renorrenal. O controle hormonal envolve, principalmente, o sistema renina-angiotensina. Os estudos sobre esses mecanismos de controle têm procurado elucidar os mecanismos fisiopatológicos envolvidos na gênese e manutenção da hipertensão arterial, visando minimizar seus efeitos deletérios.

Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii

The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation.The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular relfex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamatae microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory componente of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

The role of CO2/pH chemoreceptors in ventilatory control

It now appears that at least some members of all classes of vertebrates exhibit ventilatory responses to changes in CO2/pH per se, including fishes. With the transition from aquatic to aerial respiration, there is an increase in the sensitivity of animals to this complex of stimuli, an increase in the variety of putative receptors possibly involved in eliciting ventilatory responses and an increase in the relative importance of this complex of stimuli in the genesis of resting ventilation. The variety of CO2-sensitive chemoreceptors present in air-breathing lower vertebrates adds considerable complexity to experimental studies of ventilatory responses to CO2/pH. Because of the locations, discharge characteristics and reflex effects of the different receptor groups, most air-breathing lower vertebrates show different responses to increases in CO2/[H+] due to cerebral ischemia, anoxia, metabolic acidosis and environmental hypercarbia. In some cases the differences are only quantitative, while in other cases the responses are qualitatively very different. These differences appear to reflect differences in the relative strength of the reflexes elicited by the various receptor groups and the net sum of their modulating influences when CO2/pH are altered via different routes. Although the situation is simpler in the higher vertebrates, in all cases the input from all of the CO2/[H]-sensitive receptors appears to act as a biasing input which summates with other afferent information to modulate respiratory motor output, even in those species that breathe intermittently.

Interactions between body temperature regulation and blood acid-base status in anuran amphibians

In vertebrate evolution, the transition from aquatic to terrestrial mode of life was associated with considerable changes in the respiratory system and CO2/pH-sensitive receptors became fundamental. The present review focuses on the combined effects of hypercapnia and body temperature in anuran amphibians, that represent a key group for the transition. Recent studies have indicated that temperature affects the hypercapnic drive to breathe. Conversely, hypercapnia modulates the range of preferred body temperature of amphibians and central (CO2/pH) receptors are likely to be involved.

Phrenic nerve activity during artificial ventilation at different body temperatures and its relationships with carotid chemosensory activity

While the chemoreceptor discharges of carotid bodies in vitro are highly dependent on temperature, these chemoreceptors in situ contribute only moderately to the ventilatory adjustment to changing body temperature (Tb), probably because of the concomitant and reverse changes in natural chemoreceptor stimuli in closed-loop preparations. Accordingly, we studied the frequency of carotid chemosensory discharge (fx) and the phrenic integrated electroneurogram (IENGph) in pentobarbitone anesthetized cats, paralyzed with alcuronium and artificially ventilated, at three steady-state levels of Tb (35.5, 37.5 and 40.2 C) modifying the frequency and volume of ventilator to ontain...

The relationship of breathing pattern to central chemoreceptor activity in infantile apnea.

In order to assess the relationship of breathing pattern to the central chemoreceptor activity in infantile apnea, we studied 18 infants referred to our regional apnea center with 12 hour nocturnal pneumocardiograms and ventilatory response to 2% and 4% carbon dioxide inhalation. 70% of the infants had normal pneumocardiograms and 60% of the infants had normal ventilatory response to CO2. Nine infants (45%) had normal results in both tests. Our results indicate that in infants with a normal breathing pattern as assessed by pneumocardiogram 75% had normal central chemoreceptor activity, while 37.5% of infants with abnormal breathing pattern had abnormal ventilatory response to CO2.