OS NÚCLEOS VASOMOTORES DO BULBO E A REGULAÇÃO CARDIOVASCULAR: NOVAS EVIDÊNCIAS E NOVAS QUESTÕES

More than 30 years ago a model was proposed trying to explain how the central nervous system controls the cardiovascular adjustments. According to this model the medullary vasomotor nuclei are the main structures involved in the cardiovascular reflex control. It also shows the nucleus tractus solitarius (NTS) as being the first integrative center for the baroceptors afferents and the descending pathways from supramedullary nuclei of hypothalamus, which contribute at defense and alert reactions. The NTS exhibits excitatory projections to the caudal ventral lateral medulla (CVL) which inhibits the rostral ventral lateral medulla (RVL). The RVL is the main source of excitatory inputs to the sympathetic preganglionic neurons, being responsible for the sympathetic tonus to heart and blood vessels. Important projections from CVL to diencephalon structures (Median preoptic nucleus, Hypothalamic paraventricular nucleus, Supraoptic nucleus) also play an important role in the control of the extracellular compartment composition and volume. The gigantocellular depressor area (GiDA) is likely to be another vasomotor center involved in blood flow adjustments through direct projections to Preganglionic Sympathetic Neurons (SPN). How GiDA mediates its vasodepressor effects is unknown. In the last 10 years we have been studying the pathways and neural mechanisms related to muscle and visceral blood flow regulation. Obtained data are not compatible with the proposed model.Há mais de 30 anos foi proposto um modelo para explicar como o sistema nervoso central promove a regulação do sistema cardiovascular, onde os núcleos vasomotores do bulbo seriam as principais estruturas envolvidas no controle do reflexo cardiovascular. Segundo este modelo, o núcleo do trato solitário (NTS) é o primeiro núcleo a integrar as informações cardiovasculares vindas dos baroceptores e também parece integrar vias descendentes provenientes de núcleos superiores como o hipotálamo, importantes para as reações de alerta e defesa. Do NTS saem projeções excitatórias para a região caudoventrolateral (CVL) do bulbo, a qual inibe a região rostroventrolateral (RVL). Esta última região constitui a principal fonte de eferências excitatórias para os neurônios simpáticos pré-ganglionares (SPN), sendo responsável pelo tonus simpático para o coração e vasos. Projeções importantes do CVL para estruturas diencefálicas (núcleo preóptico mediano, núcleo paraventricular do hipotálamo e núcleo supraóptico) também estão envolvidas no controle da composição e/ou volume do compartimento extracelular. A área depressora gigantocelular (GiDA) constitui outro  possível centro vasomotor envolvido nos ajustes de fluxo sangüíneo por meio de projeções diretas para o SPN. No entanto, o meio pelo qual a GiDA exerce seu efeito vasodepressor ainda é desconhecido. Nos últimos 10 anos, nosso laboratório tem se dedicado a deslindar as vias e mecanismos neurais associados à regulação do fluxo sangüíneo visceral e muscular. Resultados obtidos ao longo destes estudos resultaram em evidências que são incompatíveis com o modelo proposto

Selective optogenetic stimulation of efferent fi bers in the vagus nerve of a large mammal

Background: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease. Objective: Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep). Methods and results: Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm 2 ; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ~6 m s 1 . Conclusions: These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation. © 2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/

Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal

BACKGROUND: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease. OBJECTIVE: Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep). METHODS AND RESULTS: Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm-2; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s-1. CONCLUSIONS: These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of the optogenetic technology for autonomic neuromodulation

Retrieval analysis of alumina ceramic-on-ceramic bearing couples

BACKGROUND AND PURPOSE: Ceramic-on-ceramic (CoC) bearings have been in use in total hip replacement (THR) for more than 40 years, with excellent long-term survivorship. Although there have been several simulator studies describing the performance of these joints, there have only been a few retrieval analyses. The aim of this study was to investigate the wear patterns, the surface properties, and friction and lubrication regimes of explanted first-generation alumina bearings. MATERIALS AND METHODS: We studied 9 explanted CoC bearings from Autophor THRs that were revised for aseptic loosening after a mean of 16 (range 7–19) years. The 3D surface roughness profiles of the femoral heads and acetabular cups (Srms, Sa, and Ssk) were measured to determine the microscopic wear. The bearings were imaged using an atomic-force microscope in contact mode, to produce a topographical map of the surfaces of the femoral heads. Friction tests were performed on the bearing couples to determine the lubrication regime under which they were operating during the walking cycle. The diametral clearances were also measured. RESULTS: 3 femoral heads showed stripe wear and the remaining 6 bearings showed minimal wear. The femoral heads with stripe wear had significantly higher surface roughness than the minimally worn bearings (0.645 vs. 0.289, p = 0.04). High diametral clearances, higher than expected friction, and mixed/boundary lubrication regimes prevailed in these retrieved bearings. INTERPRETATION: Despite the less than ideal tribological factors, these first-generation CoC bearings still showed minimal wear in the long term compared to previous retrieval analyses