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1.
Proc Natl Acad Sci U S A ; 121(3): e2312913120, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38190526

RESUMEN

General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, oophorectomy has no effect. To identify the neuronal circuits underlying sex differences, we performed whole brain c-Fos activity mapping under anesthesia in male and female mice. Consistent with a key role of the hypothalamus, we found fewer active neurons in the ventral hypothalamic sleep-promoting regions in females than in males. In humans, we demonstrate that females regain consciousness and recover cognition faster than males after identical anesthetic exposures. Remarkably, while behavioral and neurocognitive measures in mice and humans point to increased anesthetic resistance in females, cortical activity fails to show sex differences under anesthesia in either species. Cumulatively, we demonstrate that sex differences in anesthetic sensitivity are evolutionarily conserved and not reflected in conventional electroencephalographic-based measures of anesthetic depth. This covert resistance to anesthesia may explain the higher incidence of unintended awareness under general anesthesia in females.


Asunto(s)
Anestésicos , Caracteres Sexuales , Humanos , Femenino , Masculino , Animales , Ratones , Anestésicos/farmacología , Anestesia General , Testosterona/farmacología , Inconsciencia
2.
Nature ; 582(7812): 443-447, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32499642

RESUMEN

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K2P) channel family-are found in neurons1, cardiomyocytes2-4 and vascular smooth muscle cells5, where they are involved in the regulation of heart rate6, pulmonary artery tone5,7, sleep/wake cycles8 and responses to volatile anaesthetics8-11. K2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli12-15. Unlike other K2P channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation16. In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below; however, the K2P channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an 'X-gate'-created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues (243VLRFMT248) that are essential for responses to volatile anaesthetics10, neurotransmitters13 and G-protein-coupled receptors13. Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.


Asunto(s)
Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/química , Canales de Potasio de Dominio Poro en Tándem/antagonistas & inhibidores , Canales de Potasio de Dominio Poro en Tándem/química , Anestésicos/farmacología , Animales , Cristalografía por Rayos X , Conductividad Eléctrica , Femenino , Humanos , Activación del Canal Iónico/efectos de los fármacos , Modelos Moleculares , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Técnicas de Placa-Clamp , Canales de Potasio de Dominio Poro en Tándem/genética , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Xenopus laevis
3.
Proc Natl Acad Sci U S A ; 120(30): e2300058120, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37467269

RESUMEN

Unconsciousness maintained by GABAergic anesthetics, such as propofol and sevoflurane, is characterized by slow-delta oscillations (0.3 to 4 Hz) and alpha oscillations (8 to 14 Hz) that are readily visible in the electroencephalogram. At higher doses, these slow-delta-alpha (SDA) oscillations transition into burst suppression. This is a marker of a state of profound brain inactivation during which isoelectric (flatline) periods alternate with periods of the SDA patterns present at lower doses. While the SDA and burst suppression patterns have been analyzed separately, the transition from one to the other has not. Using state-space methods, we characterize the dynamic evolution of brain activity from SDA to burst suppression and back during unconsciousness maintained with propofol or sevoflurane in volunteer subjects and surgical patients. We uncover two dynamical processes that continuously modulate the SDA oscillations: alpha-wave amplitude and slow-wave frequency modulation. We present an alpha modulation index and a slow modulation index which characterize how these processes track the transition from SDA oscillations to burst suppression and back to SDA oscillations as a function of increasing and decreasing anesthetic doses, respectively. Our biophysical model reveals that these dynamics track the combined evolution of the neurophysiological and metabolic effects of a GABAergic anesthetic on brain circuits. Our characterization of the modulatory dynamics mediated by GABAergic anesthetics offers insights into the mechanisms of these agents and strategies for monitoring and precisely controlling the level of unconsciousness in patients under general anesthesia.


Asunto(s)
Anestésicos , Propofol , Humanos , Propofol/farmacología , Sevoflurano/farmacología , Inconsciencia/inducido químicamente , Anestésicos/farmacología , Encéfalo/fisiología , Electroencefalografía/métodos
4.
Neuroimage ; 289: 120556, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38423263

RESUMEN

Functional neuroimaging methods like fMRI and PET are vital in neuroscience research, but require that subjects remain still throughout the scan. In animal research, anesthetic agents are typically applied to facilitate the acquisition of high-quality data with minimal motion artifact. However, anesthesia can have profound effects on brain metabolism, selectively altering dynamic neural networks and confounding the acquired data. To overcome the challenge, we have developed a novel head fixation device designed to support awake rat brain imaging. A validation experiment demonstrated that the device effectively minimizes animal motion throughout the scan, with mean absolute displacement and mean relative displacement of 0.0256 (SD: 0.001) and 0.009 (SD: 0.002), across eight evaluated subjects throughout fMRI image acquisition (total scanning time per subject: 31 min, 12 s). Furthermore, the awake scans did not induce discernable stress to the animals, with stable physiological parameters throughout the scan (Mean HR: 344, Mean RR: 56, Mean SpO2: 94 %) and unaltered serum corticosterone levels (p = 0.159). In conclusion, the device presented in this paper offers an effective and safe method of acquiring functional brain images in rats, allowing researchers to minimize the confounding effects of anesthetic use.


Asunto(s)
Anestésicos , Vigilia , Humanos , Ratas , Animales , Vigilia/fisiología , Encéfalo/fisiología , Cabeza , Neuroimagen/métodos , Imagen por Resonancia Magnética/métodos , Anestésicos/farmacología
5.
PLoS Biol ; 19(4): e3001146, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33793545

RESUMEN

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.


Asunto(s)
Anestésicos/efectos adversos , Hipocampo/efectos de los fármacos , Consolidación de la Memoria/efectos de los fármacos , Columna Vertebral/efectos de los fármacos , Anestesia/efectos adversos , Anestésicos/farmacología , Animales , Fenómenos Electrofisiológicos/efectos de los fármacos , Femenino , Fentanilo/efectos adversos , Fentanilo/farmacología , Hipocampo/citología , Hipocampo/fisiología , Isoflurano/efectos adversos , Isoflurano/farmacología , Ketamina/efectos adversos , Ketamina/farmacología , Masculino , Medetomidina/efectos adversos , Medetomidina/farmacología , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Midazolam/efectos adversos , Midazolam/farmacología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Columna Vertebral/fisiología , Xilazina/efectos adversos , Xilazina/farmacología
6.
J Med Primatol ; 53(1): e12682, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37908039

RESUMEN

BACKGROUND: Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters. METHODS: Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection. RESULTS: While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min. CONCLUSIONS: This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed.


Asunto(s)
Anestésicos , Ketamina , Animales , Macaca fascicularis , Imidazoles/farmacología , Ketamina/farmacología , Anestésicos/farmacología , Frecuencia Cardíaca
7.
Br J Anaesth ; 132(5): 911-917, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38336517

RESUMEN

BACKGROUND: Anaesthetic drug administration is complex, and typical clinical environments can entail significant cognitive load. Colour-coded anaesthetic drug trays have shown promising results for error identification and reducing cognitive load. METHODS: We used experimental psychology methods to test the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a simulated visual search task. Effects of cognitive load were also explored through an accompanying working memory-based task. We hypothesised that colour-coded compartmentalised trays would improve drug-detection error, reduce search time, and reduce cognitive load. This comprised a cognitive load memory task presented alongside a visual search task to detect drug errors. RESULTS: All 53 participants completed 36 trials, which were counterbalanced across the two tray types and 18 different vignettes. There were 16 error-present and 20 error-absent trials, with 18 trials presented for each preloaded tray type. Syringe errors were detected more often in the colour-coded trays than in the conventional trays (91% vs 83%, respectively; P=0.006). In signal detection analysis, colour-coded trays resulted in more sensitivity to the error signal (2.28 vs 1.50, respectively; P<0.001). Confidence in response accuracy correlated more strongly with task performance for the colour-coded tray condition, indicating improved metacognitive sensitivity to task performance (r=0.696 vs r=0.447). CONCLUSIONS: Colour coding and compartmentalisation enhanced visual search efficacy of drug trays. This is further evidence that introducing standardised colour-coded trays into operating theatres and procedural suites would add an additional layer of safety for anaesthetic procedures.


Asunto(s)
Anestésicos , Jeringas , Humanos , Color , Anestésicos/farmacología , Errores de Medicación/prevención & control , Cognición
8.
Cereb Cortex ; 33(9): 5148-5162, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36222604

RESUMEN

Common marmosets are promising laboratory animals for the study of higher brain functions. Although there are many opportunities to use sedatives and anesthetics in resting brain function measurements in marmosets, their effects on the resting-state network remain unclear. In this study, the effects of sedatives or anesthetics such as midazolam, dexmedetomidine, co-administration of isoflurane and dexmedetomidine, propofol, alfaxalone, isoflurane, and sevoflurane on the resting brain function in common marmosets were evaluated using independent component analysis, dual regression analysis, and graph-theoretic analysis; and the sedatives or anesthetics suitable for the evaluation of resting brain function were investigated. The results show that network preservation tendency under light sedative with midazolam and dexmedetomidine is similar regardless of the type of target receptor. Moreover, alfaxalone, isoflurane, and sevoflurane have similar effects on resting state brain function, but only propofol exhibits different tendencies, as resting brain function is more preserved than it is following the administration of the other anesthetics. Co-administration of isoflurane and dexmedetomidine shows middle effect between sedatives and anesthetics.


Asunto(s)
Anestésicos , Dexmedetomidina , Isoflurano , Propofol , Animales , Hipnóticos y Sedantes/farmacología , Callithrix , Isoflurano/farmacología , Sevoflurano/farmacología , Midazolam/farmacología , Dexmedetomidina/farmacología , Anestésicos/farmacología , Encéfalo
9.
Paediatr Anaesth ; 34(4): 318-323, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38055618

RESUMEN

BACKGROUND/AIMS: Traditional manual methods of extracting anesthetic and physiological data from the electronic health record rely upon visual transcription by a human analyst that can be labor-intensive and prone to error. Technical complexity, relative inexperience in computer coding, and decreased access to data warehouses can deter investigators from obtaining valuable electronic health record data for research studies, especially in under-resourced settings. We therefore aimed to develop, pilot, and demonstrate the effectiveness and utility of a pragmatic data extraction methodology. METHODS: Expired sevoflurane concentration data from the electronic health record transcribed by eye was compared to an intermediate preprocessing method in which the entire anesthetic flowsheet narrative report was selected, copy-pasted, and processed using only Microsoft Word and Excel software to generate a comma-delimited (.csv) file. A step-by-step presentation of this method is presented. Concordance rates, Pearson correlation coefficients, and scatterplots with lines of best fit were used to compare the two methods of data extraction. RESULTS: A total of 1132 datapoints across eight subjects were analyzed, accounting for 18.9 h of anesthesia time. There was a high concordance rate of data extracted using the two methods (median concordance rate 100% range [96%, 100%]). The median time required to complete manual data extraction was significantly longer compared to the time required using the intermediate method (240 IQR [199, 482.5] seconds vs 92.5 IQR [69, 99] seconds, p = .01) and was linearly associated with the number of datapoints (rmanual = .97, p < .0001), whereas time required to complete data extraction using the intermediate approach was independent of the number of datapoints (rintermediate = -.02, p = .99). CONCLUSIONS: We describe a pragmatic data extraction methodology that does not require additional software or coding skills intended to enhance the ease, speed, and accuracy of data collection that could assist in clinician investigator-initiated research and quality/process improvement projects.


Asunto(s)
Anestésicos , Registros Electrónicos de Salud , Humanos , Anestésicos/farmacología
10.
Artículo en Inglés | MEDLINE | ID: mdl-38729257

RESUMEN

The time course for recovery after anesthesia is poorly described for tricaine methanesulfonate (MS-222). We suggest that the baroreflex and the heart rate variability (HRV) could be used to index the recovery of the autonomic modulation after anesthesia. We analyzed the recovery profile of behavioral and physiological parameters over time to analyze the progression of recovery after anesthesia of American bullfrogs with MS-222. Mean heart rate stabilized after 17 h, whereas the baroreflex efficiency index took 23 h and the baroreflex operating gain, 29 h. Mean arterial pressure recovered after 26 h. Power spectral density peaked at 23 h and again after 40 h. Baroreflex was a relevant component of the first phase of HRV, while autonomic modulation for resting may take longer than 40 h. We suggest that physiological recovery is a complex phenomenon with multiple progressive phases, and the baroreflex may be a useful tool to observe the first substantial recovery of post-instrumentation capacity for autonomic modulation.


Asunto(s)
Aminobenzoatos , Sistema Nervioso Autónomo , Barorreflejo , Frecuencia Cardíaca , Rana catesbeiana , Animales , Barorreflejo/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiología , Rana catesbeiana/fisiología , Aminobenzoatos/farmacología , Anestesia , Masculino , Presión Sanguínea/fisiología , Anestésicos/farmacología
11.
Acta Neurochir (Wien) ; 166(1): 77, 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38340149

RESUMEN

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.


Asunto(s)
Anestésicos , Afasia , Epilepsia , Humanos , Estudios Retrospectivos , Amobarbital/farmacología , Epilepsia/diagnóstico , Anestésicos/farmacología , Dominancia Cerebral , Imagen por Resonancia Magnética , Lateralidad Funcional , Mapeo Encefálico/métodos
12.
Int Endod J ; 57(5): 520-532, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38279778

RESUMEN

AIM: The anaesthetic success rate of an inferior alveolar nerve block (IANB) in mandibular molars with irreversible symptomatic pulpitis can be low, and postoperative pain control in teeth with this diagnosis can be challenging. This study aimed to evaluate the influence of preemptive use of dexamethasone and oral potassium diclofenac on the success of IANB. The influence of these drugs on the intensity of postoperative pain was assessed as a secondary outcome. METHODOLOGY: Eighty-four patients with mandibular molars diagnosed with irreversible symptomatic pulpitis recorded preoperative pain intensity using a cold thermal test and a modified Numerical Rating Scale (mNRS). Sixty minutes before the anaesthetic procedure, patients were randomly assigned to one of three groups based on the medication they received: dexamethasone (4 mg), diclofenac potassium (50 mg), or placebo. All patients received IANB with 4% articaine (1:200 000 epinephrine), and 15 min later, they were evaluated for pain intensity using the cold thermal test. Anaesthetic success was analysed. The pain intensity was then recorded, and endodontic treatment and provisional restoration of the tooth were executed in a single session. Patients were monitored for 6, 12, 24, 48 and 72 h using the mNRS to assess the intensity of postoperative pain. RESULTS: There was a statistically significant increase in anaesthetic success when 4 mg dexamethasone (39.3%) or 50 mg diclofenac potassium (21.4%) was used compared to the placebo group (3.6%) (p < .001), with no significant difference between the two drugs. Regarding postoperative pain, dexamethasone was superior to placebo at 6 h (p < .001), with diclofenac having an intermediate behaviour, not differing between dexamethasone and placebo (p > .05). There was no significant difference amongst the groups at 12 h (p > .05). At 24, 48 and 72 h, the effectiveness of dexamethasone and diclofenac were comparable, and both were superior to placebo (p < .001). CONCLUSION: The use of dexamethasone or diclofenac potassium was favourable in terms of increasing the success rate of inferior alveolar nerve block in cases of mandibular molars with irreversible symptomatic pulpitis and decreased the occurrence of postoperative pain when compared to the use of a placebo.


Asunto(s)
Anestesia Dental , Anestésicos , Bloqueo Nervioso , Pulpitis , Humanos , Anestesia Dental/métodos , Anestésicos/farmacología , Anestésicos Locales , Antiinflamatorios/farmacología , Dexametasona/farmacología , Diclofenaco/farmacología , Método Doble Ciego , Lidocaína , Nervio Mandibular , Diente Molar/cirugía , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Pulpitis/cirugía
13.
J Therm Biol ; 119: 103758, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38070272

RESUMEN

L-menthol is a cyclic monoterpene derived from aromatic plants, which gives a cooling sensation upon application. With this in mind, L-menthol is beginning to be considered as a potential ergogenic aid for exercise and sporting competitions, particularly in hot environments, however female-specific research is lacking. The aim of this narrative review is to summarize available literature relating to topical application of L-menthol and provide commentary on avenues of consideration relating to future research developments of topical L-menthol in female athletes. From available studies in male participants, L-menthol topical application results in no endurance exercise performance improvements, however decreases in thermal sensation are observed. Mixed results are observed within strength performance parameters. Several genetic variations and single nucleotide polymorphisms have been identified in relation to sweat production, fluid loss and body mass changes - factors which may influence topical application of L-menthol. More specifically to female athletes, genetic variations relating to sweat responses and skin thickness, phases of the menstrual cycle, and body composition indices may affect the ergogenic effects of L-menthol topical application, via alterations in thermogenic responses, along with differing tissue distribution compared to their male counterparts. This narrative review concludes that further development of female athlete research and protocols for topical application of L-menthol is warranted due to physiological and genetic variations. Such developments would benefit research and practitioners alike with further personalized sport science strategies around phases of the menstrual cycle and body composition indices, with a view to optimize ergogenic effects of L-menthol.


Asunto(s)
Anestésicos , Sustancias para Mejorar el Rendimiento , Femenino , Humanos , Mentol/farmacología , Sustancias para Mejorar el Rendimiento/farmacología , Sudoración , Sensación Térmica , Anestésicos/farmacología , Extractos Vegetales/farmacología , Atletas
14.
Vet Anaesth Analg ; 51(2): 126-134, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38114389

RESUMEN

OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.


Asunto(s)
Anestésicos , Dexmedetomidina , Hemodinámica , Labetalol , Animales , Perros , Femenino , Anestésicos/farmacología , Dexmedetomidina/farmacología , Hemodinámica/efectos de los fármacos , Isoflurano/farmacología , Labetalol/farmacología , Propofol , Estudios Prospectivos , Anestesia General/veterinaria
15.
Molecules ; 29(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930908

RESUMEN

BACKGROUND: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. METHOD: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. RESULTS: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. CONCLUSIONS: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.


Asunto(s)
Liposomas , Tensoactivos , Liposomas/química , Tensoactivos/química , Tensoactivos/farmacología , Aminoácidos/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Simulación del Acoplamiento Molecular , Anestésicos/química , Anestésicos/farmacología , Composición de Medicamentos , Pruebas de Sensibilidad Microbiana
16.
J Anesth ; 38(1): 114-124, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37843561

RESUMEN

Transcranial electrical stimulation motor-evoked potentials (Tc-MEP) monitoring is a common practice in neurosurgery to prevent postoperative neurological damage. However, the use of neuromuscular blocking agents (NMBAs) during Tc-MEP monitoring is a subject of controversy. In addition, the effectiveness of sugammadex, a selective reversal agent, in the context of Tc-MEP monitoring requires further investigation. This review aimed to clarify the considerations involved in achieving optimal Tc-MEP monitoring while ensuring patient safety. Preoperative patient selection, comorbidity assessment, motor power evaluation, and the nature of the planned surgery are critical factors. Accurate paralysis assessment, continuous NMBA infusion, and post-tetanic stimulation techniques are essential for achieving optimal partial NMB. The decision to administer an NMB during Tc-MEP monitoring necessitates a careful evaluation of the balance between accuracy and potential complications. This review emphasizes the challenges associated with NMB administration during Tc-MEP monitoring and highlights the need for personalized patient assessment.


Asunto(s)
Anestésicos , Bloqueo Neuromuscular , Humanos , Monitoreo Intraoperatorio/métodos , Potenciales Evocados Motores/fisiología , Anestésicos/farmacología , Anestesia General/métodos
17.
Fish Physiol Biochem ; 50(3): 1305-1314, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38630160

RESUMEN

In this study, the anaesthetic effects of fennel and anise essential oils were investigated on common carp. Fish (10 ± 0.45 g) were exposed to nine concentrations of essential oils (5, 10, 20, 50, 100, 200, 300, 400 and 500 mg L-1). Additionally, the histopathological effects on the fish tissues including gill, skin and hepatopancreas and physiological effects on some blood parameters (Na+, K+, Ca+2, Cl-, total plasma protein and glucose) of essential oils were investigated in carp. At the end of the experiment, fennel oil showed an anaesthetic effect at a concentration of 500 mg L-1 in carp (anaesthesia induction and recovery times were 308 and 472 s, respectively). Anise essential oil showed deep anaesthesia at a concentration of 100 mg L-1, but anaesthesia induction time was found to be very long (20 min). In addition, anise oil at concentrations above 100 mg L-1 caused 10% mortality in fish. Blood parameters except glucose level in both essential oils were unchanged during deep anaesthesia in carp. However, plasma glucose levels were found lower in fish anaesthetized with anise oil than control and fennel groups (P < 0.05). At the histopathological examination, no pathological findings were observed in any organ of fish in the fennel group. However, severe hyperemia and inflammatory cell infiltrations in gills, erosive lesions in the skin and slight inflammatory reactions in the skin were observed in the anise group. The present study demonstrated that fennel essential oil at 500 mg L-1 concentration can be used as an effective and safe anaesthetic in common carp, but anise essential oil is not suitable.


Asunto(s)
Anestésicos , Carpas , Foeniculum , Aceites Volátiles , Animales , Aceites Volátiles/farmacología , Foeniculum/química , Anestésicos/farmacología , Pimpinella/química , Branquias/efectos de los fármacos , Branquias/patología , Glucemia/análisis , Piel/efectos de los fármacos , Aceites de Plantas/farmacología , Hepatopáncreas/efectos de los fármacos , Hepatopáncreas/patología
18.
J Zoo Wildl Med ; 55(1): 102-110, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38453493

RESUMEN

The Houston toad (Anaxyrus houstonensis), a primarily terrestrial amphibian of south-central Texas, has been listed as federally endangered since 1970. Sedation is an important tool for obtaining diagnostics and providing treatment in this species. This prospective, randomized, and blinded study compared the sedative effects of SC alfaxalone (Protocol A) at approximately 12 mg/kg (median [range] = 12.70 [12.09-13.95] mg/kg] to SC alfaxalone-dexmedetomidine (Protocol AD) at approximately 12 mg/kg (median [range] = 12.68 [12.16-13.56] mg/kg) and 0.1 mg/kg (median [range] = 0.1 [0.07-0.13] mg/kg), respectively, in adult Houston toads (n = 26). Toads from Protocol AD received atipamezole SC at approximately 1 mg/kg (median [range] = 0.96 [0.75-1.25] mg/kg) 45 min postinduction, whereas toads from Protocol A received the equivalent volume of SC sterile saline at the same time point. Heart rate, gular rate, and times to first effect, loss of righting reflex, ability to position for radiographs, loss of nociception, return of righting reflex, and full recovery were recorded. A significantly greater number of toads lost righting reflex, positioned for radiographs, and lost nociception with Protocol AD compared with Protocol A. Additionally, time to return of righting reflex and time to full recovery were significantly longer with Protocol AD than with Protocol A. The protocols did not differ significantly in time to first effect, time to radiographic positioning, or time to loss of nociception. Histologic examination of four toads euthanized during the study revealed acute injection site reactions from all administered drugs, including saline. No clinical adverse reactions were observed. This study demonstrates that the combination of SC alfaxalone and dexmedetomidine results in deeper sedation than SC alfaxalone alone, but also correlates with longer recovery times despite antagonist administration.


Asunto(s)
Anestesia , Anestésicos , Dexmedetomidina , Pregnanodionas , Animales , Dexmedetomidina/farmacología , Anestésicos/farmacología , Estudios Prospectivos , Anestesia/métodos , Anestesia/veterinaria , Hipnóticos y Sedantes/farmacología , Pregnanodionas/farmacología
19.
J Zoo Wildl Med ; 55(1): 200-206, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38453503

RESUMEN

The maned sloth (Bradypus torquatus) is an endemic and endangered species of two Brazilian states, with much unknown biological information needed to direct conservation actions. Other sloth species have been studied regarding anesthesia; however, there is a lack of anesthesia research for the maned sloth. Anesthetic data were collected from 12 free-range maned sloths that were immobilized for a field examination. Individuals were anesthetized using a combination of ketamine (4.0 mg/kg) and medetomidine (0.03 mg/kg), and antagonized with atipamezole (0.1 mg/kg). Time to induction and recovery were recorded and compared with sex and age classes. After the induction and until antagonist administration, physiological parameters (rectal temperature, heart rate, respiratory rate, and oxygen saturation) were recorded every 10 min during anesthesia and were statistically evaluated over time. Induction was fast (3.21 ± 0.76), but recovery was longer (113.3 ± 18) when compared to other studies. Induction and recovery times were not different across sex or age classes. Rectal temperature, heart rate, and oxygen saturation remained stable throughout the procedure. Respiratory rate significantly decreased over time, from 18.25 ± 7.03 to 13.17 ± 3.66 movements per minute. Our results indicate that the described combination of ketamine and medetomidine is a safe and effective choice for anesthesia of maned sloths.


Asunto(s)
Anestésicos , Ketamina , Perezosos , Humanos , Animales , Medetomidina/farmacología , Ketamina/farmacología , Perezosos/fisiología , Animales Salvajes/fisiología , Anestésicos/farmacología , Inmovilización/veterinaria , Inmovilización/métodos , Hipnóticos y Sedantes/farmacología , Frecuencia Cardíaca , Anestésicos Disociativos/farmacología
20.
J Zoo Wildl Med ; 55(2): 466-470, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38875204

RESUMEN

Black-handed spider monkeys (Ateles geoffroyi ssp.) are endangered in Mexico. Safe anesthetic protocols are important for in situ and ex situ conservation problems. Such protocols are scarce in the literature; nor have safety and physiologic responses been reported. High doses and volume are a counter side for field immobilizations. We tested an anesthetic protocol with a combination of tiletamine-zolazepam (5 mg/kg) plus xylazine (1 mg/kg) in 14 black-handed spider monkeys under human care from two facilities in Mexico. Physiological parameters such as HR, RR, T, SPO2, systolic arterial pressure (), diastolic arterial pressure (DAP), and median arterial pressure (MAP) were obtained. HR and RR decreased over time, but T increased significantly during the anesthetic time for the whole group; RR and T decreased for juveniles only. Variation between individuals was observed for HR, RR, and DAP. Volume reduction of drugs was achieved compared to previously reported anesthesia protocols. Induction time was fast (6.2 ± 10.4 min) and no tail prehension was seen. Recovery was prolonged (mean and SD). Physiologic parameters remained stable throughout. The protocol proved to be safe for the chemical immobilization of black-handed spider monkeys.


Asunto(s)
Ateles geoffroyi , Tiletamina , Xilazina , Zolazepam , Animales , Tiletamina/administración & dosificación , Tiletamina/farmacología , Zolazepam/administración & dosificación , Zolazepam/farmacología , Xilazina/farmacología , Xilazina/administración & dosificación , Masculino , Femenino , Combinación de Medicamentos , Anestesia/veterinaria , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/administración & dosificación , Anestésicos/farmacología , Anestésicos/administración & dosificación , Anestésicos Combinados/administración & dosificación , Anestésicos Combinados/farmacología
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