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1.
Chem Biol Interact ; 331: 109272, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33010220

RESUMEN

A cellular model of cardiomyocytes (H9c2 cell line) and mitochondria isolated from mouse liver were used to understand the drug action of BPDZ490 and BPDZ711, two benzopyran analogues of the reference potassium channel opener cromakalim, on mitochondrial respiratory parameters and swelling, by comparing their effects with those of the parent compound cromakalim. For these three compounds, the oxygen consumption rate (OCR) was determined by high-resolution respirometry (HRR) and their impact on adenosine triphosphate (ATP) production and calcium-induced mitochondrial swelling was investigated. Cromakalim did not modify neither the OCR of H9c2 cells and the ATP production nor the Ca-induced swelling. By contrast, the cromakalim analogue BPDZ490 (1) induced a strong increase of OCR, while the other benzopyran analogue BPDZ711 (2) caused a marked slowdown. For both compounds, 1 displayed a biphasic behavior while 2 still showed an inhibitory effect. Both compounds 1 and 2 were also found to decrease the ATP synthesis, with pronounced effect for 2, while cromakalim remained without effect. Overall, these results indicate that cromakalim, as parent molecule, does not induce per se any direct effect on mitochondrial respiratory function neither on whole cells nor on isolated mitochondria whereas both benzopyran analogues 1 and 2 display totally opposite behavior profiles, suggesting that compound 1, by increasing the maximal respiration capacity, might behave as a mild uncoupling agent and compound 2 is taken as an inhibitor of the mitochondrial electron-transfer chain.


Asunto(s)
Cromakalim/análogos & derivados , Mitocondrias/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcio/farmacología , Línea Celular , Cromakalim/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Canales de Potasio/agonistas , Canales de Potasio/metabolismo , Frecuencia Respiratoria/efectos de los fármacos
3.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1068-R1077, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32320636

RESUMEN

Severe trauma can produce a postinjury "metabolic self-destruction" characterized by catabolic metabolism and hyperglycemia. The severity of the hyperglycemia is highly correlated with posttrauma morbidity and mortality. Although no mechanism has been posited to connect severe trauma with a loss of autonomic control over metabolism, traumatic injury causes other failures of autonomic function, notably, gastric stasis and ulceration ("Cushing's ulcer"), which has been connected with the generation of thrombin. Our previous studies established that proteinase-activated receptors (PAR1; "thrombin receptors") located on astrocytes in the autonomically critical nucleus of the solitary tract (NST) can modulate gastric control circuit neurons to cause gastric stasis. Hindbrain astrocytes have also been implicated as important detectors of low glucose or glucose utilization. When activated, these astrocytes communicate with hindbrain catecholamine neurons that, in turn, trigger counterregulatory responses (CRR). There may be a convergence between the effects of thrombin to derange hindbrain gastrointestinal control and the hindbrain circuitry that initiates CRR to increase glycemia in reaction to critical hypoglycemia. Our results suggest that thrombin acts within the NST to increase glycemia through an astrocyte-dependent mechanism. Blockade of purinergic gliotransmission pathways interrupted the effect of thrombin to increase glycemia. Our studies also revealed that thrombin, acting in the NST, produced a rapid, dramatic, and potentially lethal suppression of respiratory rhythm that was also a function of purinergic gliotransmission. These results suggest that the critical connection between traumatic injury and a general collapse of autonomic regulation involves thrombin action on astrocytes.


Asunto(s)
Astrocitos/efectos de los fármacos , Glucemia , Neuronas/efectos de los fármacos , Rombencéfalo/efectos de los fármacos , Trombina/farmacología , Animales , Masculino , Nervio Frénico/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Frecuencia Respiratoria/efectos de los fármacos , Núcleo Solitario/efectos de los fármacos
4.
J Anim Sci ; 98(5)2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32333770

RESUMEN

Pigs exposed to elevated ambient temperatures exhibit reduced daily gain, alterations in muscle and fat deposition, and decreased health. Negative aspects of gastrointestinal (GI) function, integrity, and permeability also occur. High-intensity sweeteners can ameliorate the negative effects of heat stress (HS) by increasing GI glucagon-like peptide-2 production while capsicum oleoresin has been shown to reduce inflammatory response. The effects of an artificial high-intensity sweetener and capsicum oleoresin (CAPS-SUC; TakTik X-Hit, Pancosma, Switzerland) on growth performance of pigs were examined. Forty-eight pigs (12 wk of age, 43.2 ± 4.3 kg) were assigned to six treatments: thermoneutral conditions (21 ± 1.1 °C; 40% to 70% relative humidity) fed ad libitum with (TN+) or without supplement (TN-), heat stress (35 ± 1 °C; 20% to 40% relative humidity) fed ad libitum with (HS+) or without supplement (HS-), and thermoneutral conditions pair-fed to HS intake with (PFTN+) or without supplement (PFTN-). Supplementation (0.1 g/kg feed) began 2 d prior to the 3-d environmental treatment period. Body weights (BWs) and blood samples were collected on days -1 and 3. Rectal temperature (RT) and respiration rate (RR) were measured thrice daily and the feed intake (FI) was recorded daily. Intestinal sections were collected for histology. Pigs in HS conditions exhibited increased RT (~1.2 °C) and RR (~2.7-fold) compared with TN and PFTN groups (P < 0.01). HS+ animals had increased RR when compared with HS- animals (P < 0.02). Heat stress decreased FI compared with TN. HS and PFTN decreased (P < 0.05) average daily gain compared with TN. Supplement did not alter the BW gain. HS and PFTN decreased (P < 0.05) Gain:Feed compared with TN during environmental treatment. Supplementation with CAPS-SUC increased Gain:Feed by 0.12 (P < 0.05). Circulating glucose concentrations tended to decrease in CAPS-SUC vs. non-supplemented HS and PFTN animals (P ≤ 0.1). Circulating insulin concentrations as well as monocyte count increased in HS compared with PFTN (P < 0.04) but did not differ from TN and likely linked to altered FI. CAPS-SUC increased basophil count (P < 0.02), irrespective of environment. Ileal villus height tended to decrease during HS and PFTN compared with TN (P < 0.08), indicating an effect of intake. Overall, CAPS-SUC supplementation increased pig feed efficiency and may improve immune response.


Asunto(s)
Capsicum/química , Suplementos Dietéticos , Trastornos de Estrés por Calor/veterinaria , Extractos Vegetales/farmacología , Edulcorantes/farmacología , Enfermedades de los Porcinos/prevención & control , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Digestión , Trastornos de Estrés por Calor/prevención & control , Respuesta al Choque Térmico , Calor , Insulina/sangre , Intestinos , Frecuencia Respiratoria/efectos de los fármacos , Edulcorantes/administración & dosificación , Porcinos
5.
Anesth Analg ; 130(5): 1147-1156, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32287122

RESUMEN

BACKGROUND: Opioid-induced respiratory depression (OIRD) is traditionally recognized by assessment of respiratory rate, arterial oxygen saturation, end-tidal CO2, and mental status. Although an irregular or ataxic breathing pattern is widely recognized as a manifestation of opioid effects, there is no standardized method for assessing ataxic breathing severity. The purpose of this study was to explore using a machine-learning algorithm for quantifying the severity of opioid-induced ataxic breathing. We hypothesized that domain experts would have high interrater agreement with each other and that a machine-learning algorithm would have high interrater agreement with the domain experts for ataxic breathing severity assessment. METHODS: We administered target-controlled infusions of propofol and remifentanil to 26 healthy volunteers to simulate light sleep and OIRD. Respiration data were collected from respiratory inductance plethysmography (RIP) bands and an intranasal pressure transducer. Three domain experts quantified the severity of ataxic breathing in accordance with a visual scoring template. The Krippendorff alpha, which reports the extent of interrater agreement among N raters, was used to assess agreement among the 3 domain experts. A multiclass support vector machine (SVM) was trained on a subset of the domain expert-labeled data and then used to quantify ataxic breathing severity on the remaining data. The Vanbelle kappa was used to assess the interrater agreement of the machine-learning algorithm with the grouped domain experts. The Vanbelle kappa expands on the Krippendorff alpha by isolating a single rater-in this case, the machine-learning algorithm-and comparing it to a group of raters. Acceptance criteria for both statistical measures were set at >0.8. The SVM was trained and tested using 2 sensor inputs for the breath marks: RIP and intranasal pressure. RESULTS: Krippendorff alpha was 0.93 (95% confidence interval [CI], 0.91-0.95) for the 3 domain experts. Vanbelle kappa was 0.98 (95% CI, 0.96-0.99) for the RIP SVM and 0.96 (0.92-0.98) for the intranasal pressure SVM compared to the domain experts. CONCLUSIONS: We concluded it may be feasible for a machine-learning algorithm to quantify ataxic breathing severity in a manner consistent with a panel of domain experts. This methodology may be helpful in conjunction with traditional measures to identify patients experiencing OIRD.


Asunto(s)
Algoritmos , Analgésicos Opioides/efectos adversos , Aprendizaje Automático , Insuficiencia Respiratoria/inducido químicamente , Frecuencia Respiratoria/efectos de los fármacos , Índice de Severidad de la Enfermedad , Adulto , Analgésicos Opioides/administración & dosificación , Femenino , Humanos , Masculino , Insuficiencia Respiratoria/fisiopatología , Frecuencia Respiratoria/fisiología
6.
Acta Vet Scand ; 62(1): 14, 2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32164761

RESUMEN

BACKGROUND: General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory effects of propofol-ketamine-dexmedetomidine and alfaxalone-ketamine-dexmedetomidine in pigs. Sixteen pigs premedicated with ketamine 15 mg/kg and midazolam 1 mg/kg intramuscularly were anaesthetised with propofol or alfaxalone to allow endotracheal intubation, followed by propofol 8 mg/kg/h or alfaxalone 5 mg/kg/h in combination with ketamine 5 mg/kg/h and dexmedetomidine 4 µg/kg/h given as a continuous infusion for 60 min. The pigs breathed spontaneously with an FIO2 of 0.21. Oxygen saturation (SpO2), end-tidal CO2 concentration (PE'CO2), respiratory rate (fR) and inspired tidal volume (VT) were measured, and statistically compared between treatments. If the SpO2 dropped below 80% or if PE'CO2 increased above 10.0 kPa, the pigs were recorded as failing to complete the study, and time to failure was statistically compared between treatments. RESULTS: Alfaxalone treated pigs had significantly higher respiratory rates and lower PE'CO2 than propofol treated pigs, with a fR being 7.3 /min higher (P = 0.01) and PE'CO2 0.8 kPa lower (P = 0.05). SpO2 decreased by 0.6% and fR by 1.0 /min per kg increase in body weight in both treatment groups. Three of eight propofol treated and two of eight alfaxalone treated pigs failed to complete the study, and times to failure were not significantly different between treatments (P = 0.75). CONCLUSIONS: No major differences in respiratory variables were found when comparing treatments. Respiratory supportive measures must be available when using both protocols.


Asunto(s)
Anestesia General/métodos , Anestésicos Generales , Respiración/efectos de los fármacos , Anestésicos Generales/administración & dosificación , Anestésicos Generales/farmacología , Animales , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacología , Quimioterapia Combinada , Femenino , Ketamina/administración & dosificación , Ketamina/farmacología , Masculino , Pregnanodionas/administración & dosificación , Pregnanodionas/farmacología , Propofol/administración & dosificación , Propofol/farmacología , Frecuencia Respiratoria/efectos de los fármacos , Porcinos
7.
J Zoo Wildl Med ; 51(1): 96-101, 2020 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-32212551

RESUMEN

Alfaxalone is a neurosteroid anesthetic agent that has been extensively used in both human and veterinary medicine for more than 50 yr. Previous studies involving avian species demonstrated various dose ranges and multiple routes of administration. The aim of this study was to evaluate the short-term sedative, cardiorespiratory, and thermoregulatory effects of an intramuscular injection of alfaxalone on budgerigars (Melopsittacus undulatus). A crossover study was performed with a sample size of 10 male budgerigars, previously determined to be healthy based on physical examination. Alfaxalone was administered intramuscularly at two doses: 15 and 20 mg/kg. The lower dose resulted in mild to moderate sedation for 29 ± 5 min, whereas the higher dose resulted in moderate to profound sedation for 29 ± 7 min. A statistically significant decrease in heart rate was observed 2 min after administration of alfaxalone at 15 mg/kg; however, this finding was noted to be transient. A statistically significant decrease in respiratory rate was observed at 6 and 10 min after injection in both groups. Cloacal temperature measurement with a digital thermometer and eye temperature calculated from thermographic images demonstrated a decrease in body temperature over time but was not found to be statistically significant. Intramuscular use of alfaxalone proved to provide short-term sedation in budgerigars, with statistically significant but clinically mild cardiorespiratory effects. Due to a significant decrease in body temperature, active warming is recommended when using alfaxalone in budgerigars.


Asunto(s)
Anestésicos/administración & dosificación , Temperatura Corporal/efectos de los fármacos , Sedación Consciente/veterinaria , Melopsittacus/fisiología , Pregnanodionas/administración & dosificación , Frecuencia Respiratoria/efectos de los fármacos , Animales , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Inyecciones Intramusculares/veterinaria , Masculino , Distribución Aleatoria
8.
Epilepsia ; 61(3): 572-588, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32030748

RESUMEN

OBJECTIVE: Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO2 ) in low-risk and high-risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice. METHODS: Heart rate and SaO2 were determined noninvasively with ECGenie and pulse oximetry. Respiration was determined with noninvasive airway mechanics technology. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry. RESULTS: Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity. SIGNIFICANCE: High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.


Asunto(s)
Apnea/genética , Bradicardia/genética , Epilepsia/genética , Hipoxia/genética , Canal de Potasio Kv.1.1/genética , Muerte Súbita e Inesperada en la Epilepsia , Animales , Apnea/fisiopatología , Bradicardia/fisiopatología , Epilepsia/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Área Hipotalámica Lateral/metabolismo , Área Hipotalámica Lateral/patología , Hipoxia/fisiopatología , Cloruro de Metacolina/toxicidad , Ratones , Ratones Noqueados , Neuronas/metabolismo , Neuronas/patología , Antagonistas de los Receptores de Orexina/farmacología , Orexinas/metabolismo , Oximetría , Oxígeno , Sistema Nervioso Parasimpático/fisiopatología , Parasimpaticomiméticos/toxicidad , Frecuencia Respiratoria/efectos de los fármacos , Convulsiones/inducido químicamente
9.
J Zoo Wildl Med ; 50(4): 988-992, 2020 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-31926533

RESUMEN

Five free-ranging male (subadults, n = 3; adults, n = 2) plains zebras (Equus quagga) were immobilized using a combination of etorphine (0.017 mg/kg), medetomidine (0.017 mg/kg), and azaperone (0.24 mg/kg) by means of a blank cartridge-fired projector. Time to recumbency was recorded and a descriptive score used to assess the quality of immobilization, manipulation, maintenance, and recovery. Physiological parameters were recorded at 5-min intervals for 20 min. At the end of the procedure, naltrexone (0.23 mg/kg) was administered intramuscularly and time to standing documented. The combination evaluated in this study allowed for successful immobilization and safe recovery of all animals, including during the subsequent 15 days. Despite the good outcome in this pilot study, as a result of the periodic apneic events and hypercapnia documented in the zebras, the authors suggest that physiological parameters be thoroughly monitored when using this protocol. Further studies are needed to improve upon chemical immobilization protocols in free-ranging plains zebras.


Asunto(s)
Azaperona/farmacología , Equidae , Etorfina/farmacología , Inmovilización/veterinaria , Medetomidina/farmacología , Animales , Animales Salvajes , Azaperona/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Combinación de Medicamentos , Etorfina/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Masculino , Medetomidina/administración & dosificación , Proyectos Piloto , Frecuencia Respiratoria/efectos de los fármacos
10.
Medicine (Baltimore) ; 99(4): e18657, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977855

RESUMEN

BACKGROUND: To systematically evaluate the clinical efficacy of salbutamol treatment in infants with bronchiolitis. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the use of salbutamol in infants with bronchiolitis was performed. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of RCTs. Data were extracted and meta-analyzed using STATA version 12.0 (StataCorp, College Station, TX). RESULTS: Thirteen RCTs, including a total of 977 participants, were assessed in the present meta-analysis. Results indicated that salbutamol therapy for bronchiolitis in infants led to an increase in respiratory rate (weighted mean difference [WMD] 2.26 [95% confidence interval {CI} 0.36-4.16]) and higher heart rate (WMD 12.15 [95% CI 9.24-15.07]). However, as a selective ß2-agonist, salbutamol did not improve the clinical severity score of infants with bronchiolitis (WMD -0.11 [95% CI -0.26 to 0.03]), length of hospital stay (WMD 0.12 [95% CI -0.32 to 0.56]), or oxygen saturation (WMD 0.20 [95% CI -0.35 to 0.75]). CONCLUSION: Based on the results of this systematic review, the use of salbutamol had no effect on bronchiolitis in children <24 months of age. Moreover, the treatment can also lead to side effects, such as high heart rate. As such, salbutamol should not be recommended for treatment of bronchiolitis in infants.


Asunto(s)
Albuterol/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Lactante , Tiempo de Internación , Oxígeno/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Frecuencia Respiratoria/efectos de los fármacos , Índice de Severidad de la Enfermedad
11.
Respir Physiol Neurobiol ; 271: 103310, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31568840

RESUMEN

The neuropeptide relaxin-3 is expressed by the pontine nucleus incertus. Relaxin-3 and synthetic agonist peptides modulate arousal and cognitive processes via activation of the relaxin-family peptide 3 receptor (RXFP3). Despite the presence of RXFP3 in the nucleus of the solitary tract (NTS), the ability of RXFP3 to modulate NTS-mediated cardiorespiratory functions has not been explored. Therefore, we examined the effects of bilateral microinjections of the selective agonist, RXFP3-A2 (40 µM, 100 nL/side), into the NTS in perfused working-heart-brainstem-preparations from rats (n = 6), while recording phrenic, vagal, and thoracic sympathetic chain activity (PNA, VNA, t-SCA) and heart rate (HR). RXFP3-A2 significantly increased respiratory rate and shortened post-inspiratory VNA. RXFP3-A2 in the NTS also significantly enhanced arterial chemoreceptor reflex (a-CR)-mediated tachypnea. However, RXFP3-A2 had no significant effect on HR and t-SCA at baseline or during the a-CR. These data represent the first evidence that RXFP3 activation in the NTS can selectively modulate respiration at baseline and during reflex behaviour.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Frecuencia Respiratoria/fisiología , Núcleo Solitario/metabolismo , Animales , Células Quimiorreceptoras/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Microinyecciones/métodos , Técnicas de Cultivo de Órganos , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores de Péptidos/agonistas , Frecuencia Respiratoria/efectos de los fármacos , Núcleo Solitario/efectos de los fármacos
12.
J Feline Med Surg ; 22(2): 108-113, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30744474

RESUMEN

OBJECTIVES: The aim of this study was to describe the sedative and some physiological effects of tiletamine-zolazepam following buccal administration (BA) in cats. METHODS: Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine-zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. RESULTS: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. CONCLUSIONS AND RELEVANCE: BA of tiletamine-zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.


Asunto(s)
Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes , Frecuencia Respiratoria/efectos de los fármacos , Tiletamina , Zolazepam , Administración Bucal , Animales , Gatos , Sedación Consciente/métodos , Sedación Consciente/veterinaria , Estudios Cruzados , Combinación de Medicamentos , Femenino , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Masculino , Tiletamina/administración & dosificación , Tiletamina/farmacología , Zolazepam/administración & dosificación , Zolazepam/farmacología
13.
N Z Vet J ; 68(3): 198-202, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31778611

RESUMEN

Aim: To evaluate the sedative and clinical effects of I/V xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.Methods: Seven clinically healthy, male adult miniature donkeys with a mean age of 6 years and weight of 105 kg, were assigned to five I/V treatments in a randomised, cross-over design. They received either 1.1 mg/kg xylazine, 20 µg/kg detomidine, 10 µg/kg medetomidine, 5 µg/kg dexmedetomidine or saline, with a washout period of ≥7 days. The degree of sedation was scored using a 4-point scale by three observers, and heart rate (HR), respiration rate (RR), rectal temperature and capillary refill time (CRT) were recorded immediately before and 5, 10, 15, 30, 60, 90 and 120 minutes after drug administration.Results: All saline-treated donkeys showed no sedation at any time, whereas the donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine had mild or moderate sedation between 5 and 60 minutes after treatment, and no sedation after 90 minutes. All animals recovered from sedation without complication within 2 hours. The mean HR and RR of saline-treated donkeys did not change between 0 and 120 minutes after administration, but the mean HR and RR of donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine declined between 5 and 60 minutes after drug administration. The mean rectal temperature of all treated donkeys did not change between 0 and 120 minutes after administration. The CRT for all donkeys was ≤2 seconds at all times following each treatment.Conclusions and clinical relevance: Administration of xylazine at 1.1 mg/kg, detomidine at 20 µg/kg, medetomidine at 10 µg/kg and dexmedetomidine at 5 µg/kg resulted in similar sedation in miniature donkeys. Therefore any of the studied drugs could be used for sedation in healthy miniature donkeys.


Asunto(s)
Equidae/fisiología , Hipnóticos y Sedantes/farmacología , Imidazoles/farmacología , Xilazina/farmacología , Animales , Dexmedetomidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Irán , Masculino , Medetomidina/farmacología , Frecuencia Respiratoria/efectos de los fármacos
14.
Trop Anim Health Prod ; 52(4): 1661-1668, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31853788

RESUMEN

This study aimed to evaluate chromium supplementation on productive, reproductive, and metabolic parameters at lactating Girolando cows subjected to heat stress conditions in a climatic chamber. Thirty-six lactating Girolando cows were subjected to two sequential trials. In trial 1 (thermoneutral environment), the effect of chromium supplementation was evaluated (0 vs. 0.50 mg/kg of dry matter). In trial 2, the cows were fed the same diets, but they were divided into three environmental conditions: heat stress conditions in climatic chamber, fed ad libitum (HS); thermoneutral environment, fed ad libitum (TN); and thermoneutral environment, pair-fed (PF). In thermoneutral conditions, chromium supplementation did not affect productive or metabolic parameters, although supplemented cows had lower viability of oocytes (65.11 ± 0.08% vs. 76.86 ± 0.08%). During heat stress, chromium supplementation lowered plasma glucose levels (61.17 ± 1.90 vs. 67.11 ± 1.90 mg/dL), and increased the insulin:glucose ratio (0.39 ± 0.04 vs. 0.27 ± 0.04). Cows fed the control diet in the HS group had higher vaginal temperature values (39.40 ± 0.10 °C) than the cows in the TN group and PF group (38.89 ± 0.10 °C and 38.85 ± 0.11 °C, respectively). However, supplemented cows heat-stressed maintained the same vaginal temperature as cows in thermoneutral conditions. In conclusion, chromium supplementation improved glucose metabolism and prevented body temperature increases under heat stress conditions.


Asunto(s)
Temperatura Corporal/efectos de los fármacos , Cromo/uso terapéutico , Suplementos Dietéticos , Trastornos de Estrés por Calor/prevención & control , Respuesta al Choque Térmico , Animales , Bovinos , Cromo/farmacología , Dieta/veterinaria , Femenino , Glucosa , Calor , Insulina , Lactancia , Frecuencia Respiratoria/efectos de los fármacos , Estrés Fisiológico , Temperatura
15.
Vet Rec ; 186(16): 534, 2020 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-31879322

RESUMEN

BACKGROUND: The aims of this study were evaluate cardiopulmonary, sedative and antinociceptive effects of dexmedetomidine-lidocaine combination via lumbosacral epidural injection in sheep. METHODS: Six Santa Inês breed sheep, 16±6 months old and weighing 42.2 ± 5.7 kg were used. Sheep were subjected to epidural anaesthesia with three treatments: L, lidocaine (1.2 mg/kg), D, dexmedetomidine (2.5 µg/kg) or DL, dexmedetomidine plus lidocaine (2.5 µg/kg + 1.2 mg/kg). Drugs were injected via pre-placed lumbosacral epidural catheters. Cardiopulmonary, arterial blood gases, electrolytes, degree of sedation and antinociceptive aspects were measured before drug administration (T0) and then at 15, 30, 60 and 120 min after drug injection (T15-T120) in all treatments and at T0 to T240 in DL. RESULTS: There were significantly increases in PaCO2 at times T60 and T120 in D, and at T30-T120 in DL, compared to baseline. The antinociceptive effects were observed up to 240 min in DL and 60 min in L, and were more intense in DL. Treatment D provided analgesia only in the perineal region, and only at T15. CONCLUSION: The combination of DEX with lidocaine produced similar cardiopulmonary changes compared with either drug alone, but with greater and more prolonged antinociceptive effects.


Asunto(s)
Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacología , Lidocaína/administración & dosificación , Lidocaína/farmacología , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Combinación de Medicamentos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Inyecciones Epidurales/veterinaria , Masculino , Dolor/tratamiento farmacológico , Dolor/veterinaria , Frecuencia Respiratoria/efectos de los fármacos , Ovinos
16.
Res Vet Sci ; 128: 177-182, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31812610

RESUMEN

The aim of this prospective, randomized, blinded crossover study was compare the cardiopulmonary and sedative effects of ketamine in combination with acepromazine, diazepam, dexmedetomidine, midazolam or xylazine, injected intramuscularly in rabbits, using eight one-year-old male New Zealand rabbits (4.1 ± 0.40 kg). All treatments included ketamine (K; 30 mg/kg) in combination with one of the following: acepromazine 0.5 mg/kg (treatment KA); diazepam 1 mg/kg (KD); dexmedetomidine 0.025 mg/kg (KDex); midazolam 1 mg/kg (KM); or xylazine 3 mg/kg (KX) mixed in the same syringe and injected intramuscularly. Cardiopulmonary variables, blood gases and sedative scores were measured before injection (T0 or baseline) and every 10 min thereafter, over a 60-min period. There were reductions in heart rate, compared with the baseline, at all evaluation times in treatment KX. Treatments KDex, KM and KX presented reductions in respiratory rate at all evaluation times, in comparison with the baseline. There were reductions in mean arterial pressure in KA and KX at times T10-T60 and in PaO2 in KDex, KM and KX at T10-T50. The sedation scores were similar in KA, KDex, KM and KX at T10-T20. Ketamine in combination with acepromazine, dexmedetomidine, midazolam or xylazine promoted similar sedative effects for twenty minutes, but the α2-agonists can promote hypoxemia.


Asunto(s)
Anestesia/veterinaria , Anestésicos/farmacología , Ketamina/farmacología , Acepromazina/administración & dosificación , Acepromazina/efectos adversos , Acepromazina/farmacología , Periodo de Recuperación de la Anestesia , Animales , Presión Arterial/efectos de los fármacos , Estudios Cruzados , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Dexmedetomidina/farmacología , Combinación de Medicamentos , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes , Hipoxia , Inyecciones Intramusculares/veterinaria , Ketamina/administración & dosificación , Ketamina/efectos adversos , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Midazolam/farmacología , Estudios Prospectivos , Conejos , Frecuencia Respiratoria/efectos de los fármacos , Xilazina/administración & dosificación , Xilazina/efectos adversos , Xilazina/farmacología
17.
Am J Vet Res ; 80(12): 1089-1098, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31763939

RESUMEN

OBJECTIVE: To compare anesthetic effects of alfaxalone-ketamine-dexmedetomidine (AKD) and alfaxalone-butorphanol-midazolam (ABM) in naked mole-rats (Heterocephalus glaber). ANIMALS: 20 naked mole-rats. PROCEDURES: Naked mole-rats received AKD (alfaxalone, 2 mg/kg; ketamine, 20 mg/kg; and dexmedetomidine, 0.02 mg/kg; n = 10) or ABM (alfaxalone, 2 mg/kg; butorphanol, 2 mg/kg; and midazolam, 1 mg/kg; 9) IM; 1 animal was removed from the study. Atipamezole (I mg/kg) and flumazenil (0.1 mg/kg) were administered 40 minutes after anesthetic induction (defined as loss of the righting reflex) with AKD and ABM, respectively. Heart rate, respiratory rate, oxygen saturation, and reflexes were recorded every 5 minutes. RESULTS: The ABM group had significantly longer median times for induction and recovery than the AKD group. Administration of ABM resulted in significantly lower respiratory rates than administration of AKD from time of anesthetic induction to 10 minutes after induction. Respiratory rate significantly decreased in the AKD group from I0 minutes after induction through the end of the anesthetic period but did not change over time in the ABM group. Males had higher respiratory rates in both groups. Loss of the righting reflex was still evident 40 minutes after induction in both groups. In the AKD group, all tested reflexes were absent from I0 to 40 minutes after induction; the ABM group had variable reflexes that recovered within individual animals over time. CONCLUSIONS AND CLINICAL RELEVANCE: Both AKD and ABM provided effective immobilization in naked mole-rats, but AKD appeared to provide more consistent and deeper anesthesia, compared with administration of ABM.


Asunto(s)
Anestésicos/administración & dosificación , Anestésicos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intramusculares , Ratas Topo , Frecuencia Respiratoria/efectos de los fármacos , Animales , Butorfanol/administración & dosificación , Butorfanol/farmacología , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacología , Femenino , Ketamina/administración & dosificación , Ketamina/farmacología , Masculino , Midazolam/administración & dosificación , Midazolam/farmacología , Pregnanodionas/administración & dosificación , Pregnanodionas/farmacología
18.
J Pediatr Ophthalmol Strabismus ; 56(6): 378-382, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31743406

RESUMEN

PURPOSE: To investigate the effects of topical application of ophthalmic 5% povidone-iodine eye drops, which has been reported to cause apnea in spontaneously breathing children during general anesthesia. METHODS: The authors conducted a randomized, controlled, single-blinded study comparing the effect of balanced salt solution eye drops and povidone-iodine eye drops on respiration in spontaneously breathing children during general anesthesia with sevoflurane via a laryngeal mask airway. Fifty patients received balanced salt solution eye drops and 50 patients received 5% povidone-iodine eye drops. RESULTS: None of the control patients had a significant change in respiration. Thirty of the 50 (60%) povidone-iodine patients had a slowing of respiration within the first 6 breaths after eye drop instillation (P < .001). The median time of respiratory pause in those 30 patients was 18.5 seconds (range: 4.36 to 96.2 seconds). Among the povidone-iodine patients, children with a history of a prior tonsillectomy and adenoidectomy and/or bilateral myringotomy had a 7.2 times greater chance of experiencing a change in respiration after instillation of the povidone-iodine eye drops. CONCLUSIONS: Topical application of 5% povidone-iodine eye drops causes a slowing and pause in spontaneous ventilation in a majority of children prior to strabismus surgery. This may represent activation of the diving reflex. [J Pediatr Ophthalmol Strabismus. 2019;56(6):378-382.].


Asunto(s)
Procedimientos Quirúrgicos Oftalmológicos , Povidona Yodada/administración & dosificación , Cuidados Preoperatorios/métodos , Frecuencia Respiratoria/efectos de los fármacos , Estrabismo/tratamiento farmacológico , Adolescente , Anestesia General/métodos , Antiinfecciosos Locales/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Instilación de Medicamentos , Masculino , Soluciones Oftálmicas , Método Simple Ciego , Estrabismo/fisiopatología , Estrabismo/cirugía , Resultado del Tratamiento
19.
PLoS One ; 14(10): e0224035, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31626685

RESUMEN

We investigated the hemodynamic and mortality effects of continuous ketamine infusion in critically ill pediatric patients. We conducted a retrospective cohort study in a tertiary pediatric intensive care unit (PICU). Patients who used continuous sedative from 2015 to 2017 for 24 hours or more were included. We compared blood pressure, heart and respiratory rates, vasogenic medications, and sedation and pain scores for 12 hours before and after initiation of continuous ketamine. The mortality rates for continuous ketamine and Non-ketamine groups were compared by multivariate logistic regression. A total of 240 patients used continuous sedation, and 82 used continuous ketamine. The median infusion rate of ketamine was 8.1 mcg/kg/min, and the median duration was 6 days. Heart rates (138 vs. 135 beat/minute, P = .033) and respiratory rates (31 vs. 25 respiration/minute, P = .001) decreased, but blood pressure (99.9 vs. 101.1 mm Hg, P = .124) and vasogenic medications did not change after ketamine infusion. Continuous ketamine was not a significant risk factor for mortality (hazard ratio 1.352, confidence interval 0.458-3.996). Continous ketamine could be used in PICU without hemodynamic instability. Further studies in randomized controlled design about the effects of continuous ketamine infusion on hemodynamic changes, sedation, and mortality are required.


Asunto(s)
Enfermedad Crítica , Hemodinámica/efectos de los fármacos , Ketamina/farmacología , Presión Sanguínea/efectos de los fármacos , Preescolar , Femenino , Cardiopatías/mortalidad , Cardiopatías/patología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/uso terapéutico , Lactante , Unidades de Cuidado Intensivo Pediátrico , Ketamina/uso terapéutico , Modelos Logísticos , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/patología , Masculino , Modelos de Riesgos Proporcionales , Frecuencia Respiratoria/efectos de los fármacos , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria
20.
Sci Rep ; 9(1): 14122, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31575947

RESUMEN

Opioid drugs are the mainstay of pain management but present the side-effect of respiratory depression that can be lethal with overdose. In addition to their respiratory effect, opioids also induce a profound sedative state and produce electrocortical features characteristic of a state of reduced brain arousal, similar to anaesthesia or sleep. In such states, respiratory activity depends more on the integrity of the brainstem respiratory network than it does during wakefulness. Accordingly, we propose that sedation by fentanyl induces specific electrocortical changes consistent with reduced brain arousal, and that the magnitude of respiratory depression is associated with distinct electrocortical changes. To these aims, we determined the effects of systemic injections of fentanyl (dosage 100 µg ·kg) versus control on electrocortical  and respiratory activities of freely-behaving rats. We found that fentanyl induced electrocortical changes that differed from those observed in sleep or wakefulness. Fentanyl increased δ (1-3 Hz) frequency power (P < 0.001), but reduced α (7.5-13.5 Hz) and ß2 (20-30 Hz) powers (P = 0.012 and P < 0.001, respectively), when compared to wakefulness. Interestingly, respiratory rate depression by fentanyl was significantly correlated with increased θ power (R = 0.61, P < 0.001), therefore showing a clear association between electrocortical activity and the magnitude of respiratory rate depression. Overall, we provide new evidence linking specific electrocortical changes to the severity of respiratory depression by opioids, which highlights the importance of considering the cortical and subcortical effects of opioids in addition to their impacts on breathing when evaluating opioid-induced respiratory depression.


Asunto(s)
Analgésicos Opioides/farmacología , Fentanilo/farmacología , Insuficiencia Respiratoria/tratamiento farmacológico , Frecuencia Respiratoria/efectos de los fármacos , Anestesia/métodos , Animales , Nivel de Alerta/efectos de los fármacos , Tronco Encefálico/efectos de los fármacos , Masculino , Ratas , Ratas Wistar
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