RESUMEN
Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock.
RESUMEN
The amount of aerosol generation associated with the use of positive pressure ventilation via a supraglottic airway device has not been quantified. We conducted a two-group, two-centre, prospective cohort study in which we recruited 21 low-risk adult patients scheduled for elective surgery under general anaesthesia with second-generation supraglottic airway devices. An optical particle sizer and an isokinetic sampling probe were used to record particle concentrations per second at different size distributions (0.3-10 µm) during use as well as baseline levels during two common activities (conversation and coughing). There was a median (IQR [range]) peak increase of 2.8 (1.5-4.5 [1-28.1]) and 4.1 (2.0-7.1 [1-18.2]) times background concentrations during SAD insertion and removal. Most of the particles generated during supraglottic airway insertion (85.0%) and removal (85.3%) were < 3 µm diameter. Median (IQR [range]) aerosol concentration generated by insertion (1.1 (0.6-5.1 [0.2-22.3]) particles.cm-3 ) and removal (2.1 (0.5-3.0 [0.1-18.9]) particles.cm-3 ) of SADs were significantly lower than those produced during continuous talking (44.5 (28.3-70.5 [2.0-134.5]) particles.cm-3 ) and coughing (141.0 (98.3-202.8 [4.0-296.5]) particles.cm-3 ) (p < 0.001). The aerosol levels produced were similar with the two devices. The proportion of easily inhaled and small particles (<1 µm) produced during insertion (57.5%) and removal (57.5%) was much lower than during talking (99.1%) and coughing (99.6%). These results suggest that the use of supraglottic airway devices in low-risk patients, even with positive pressure ventilation, generates fewer aerosols than speaking and coughing in awake patients.
Asunto(s)
Intubación Intratraqueal , Aerosoles y Gotitas Respiratorias , Adulto , Humanos , Intubación Intratraqueal/métodos , Estudios Prospectivos , Respiración con Presión Positiva , Ventilación con Presión Positiva Intermitente , Tos/etiologíaRESUMEN
Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.
Asunto(s)
Propofol , Humanos , Remifentanilo , Anestesia Intravenosa , Piperidinas , Analgésicos Opioides , Anestesia General , Hipnóticos y Sedantes , Anestésicos IntravenososRESUMEN
Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.
Asunto(s)
Anestesia de Conducción/métodos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Analgésicos Opioides/administración & dosificación , Anestesia de Conducción/normas , Anestesia Local/métodos , Anestesia Local/normas , Anestésicos Locales/farmacocinética , Antiinflamatorios no Esteroideos/administración & dosificación , Quimioterapia Combinada , Humanos , Magnesio/administración & dosificación , Bloqueo Nervioso/métodos , Bloqueo Nervioso/normasAsunto(s)
Anestesia/métodos , Anestesia/normas , Anestésicos/administración & dosificación , Anestésicos/farmacocinética , Vías de Administración de Medicamentos , Composición de Medicamentos/métodos , Composición de Medicamentos/normas , Humanos , Infusiones Intravenosas/métodos , Infusiones Intravenosas/normasAsunto(s)
Anestésicos , Hipertermia Maligna , Susceptibilidad a Enfermedades , Feto , Humanos , Hipertermia , Hipertermia Maligna/genéticaRESUMEN
Gonadotropin-releasing hormone (GnRH) neurons are the final common conduit from the central nervous system in the reproductive axis, controlling luteinizing hormone (LH) secretion from the gonadotropes of the anterior pituitary. Although it is generally accepted that undernutrition inhibits GnRH/LH secretion, the central mechanisms that underlie the link between energy balance and reproduction remain to be fully elucidated. Sheep have been a longstanding and invaluable animal model for examination of the nutritional regulation of GnRH/LH secretion, given their ability to serve a biomedical and agricultural purpose. In this review, we summarize work that has used the ovine model to examine the central mechanisms whereby undernutrition regulates GnRH/LH secretion. Specifically, we focus our attention to the arcuate nucleus of the hypothalamus and on neurons that express kisspeptin, neurokinin B, dynorphin, proopiomelanocortin, and neuropeptide y/agouti-related peptide (NPY/AgRP). We examine their roles in mediating the effects of leptin and insulin and their effects on LH during undernutrition, as well as their regulation under conditions of undernutrition. This review will also highlight the interactions between the aforementioned neuronal networks themselves, which may be important for our understanding of the roles each play in relaying information regarding energy status during times of undernutrition to ultimately regulate GnRH/LH secretion.
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Hormona Liberadora de Gonadotropina/fisiología , Hormona Luteinizante/fisiología , Desnutrición/veterinaria , Reproducción/fisiología , Ovinos/fisiología , AnimalesRESUMEN
Neurokinin B (NKB) is essential for human reproduction and has been shown to stimulate luteinising hormone (LH) secretion in several species, including sheep. Ewes express the neurokinin-3 receptor (NK3R) in the retrochiasmatic area (RCh) and there is one report that placement of senktide, an NK3R agonist, therein stimulates LH secretion that resembles an LH surge in ewes. In the present study, we first confirmed that local administration of senktide to the RCh produced a surge-like increase in LH secretion, and then tested the effects of this agonist in two other areas implicated in the control of LH secretion and where NK3R is found in high abundance: the preoptic area (POA) and arcuate nucleus (ARC). Bilateral microimplants containing senktide induced a dramatic surge-like increase in LH when given in the POA similar to that seen with RCh treatment. By contrast, senktide treatment in the ARC resulted in a much smaller but significant increase in LH concentrations suggestive of an effect on tonic secretion. The possible role of POA and RCh NK3R activation in the LH surge was next tested by treating ewes with SB222200, an NK3R antagonist, in each area during an oestradiol-induced LH surge. SB222200 in the RCh, but not in the POA, reduced the LH surge amplitude by approximately 40% compared to controls, indicating that NK3R activation in the former region is essential for full expression of the pre-ovulatory LH surge. Based on these data, we propose that the actions of NKB in the RCh are an important component of the pre-ovulatory LH surge in ewes.