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1.
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
2.
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
3.
Life Sci ; 240: 117068, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31751583

RESUMEN

AIMS: Bradycardia contributes to tachy-brady arrhythmias or sinus arrest during heart failure (HF). Sinoatrial node (SAN) adenosine A1 receptors (ADO A1Rs) are upregulated in HF, and adenosine is known to exert negative chronotropic effects on the SAN. Here, we investigated the role of A1R signaling at physiologically relevant ADO concentrations on HF SAN pacemaker cells. MAIN METHODS: Dogs with tachypacing-induced chronic HF and normal controls (CTL) were studied. SAN tissue was collected for A1R and GIRK mRNA quantification. SAN cells were isolated for perforated patch clamp recordings and firing rate (bpm), slope of slow diastolic depolarization (SDD), and maximum diastolic potential (MDP) were measured. Action potentials (APs) and currents were recorded before and after addition of 1 and 10 µM ADO. To assess contributions of A1R and G protein-coupled Inward Rectifier Potassium Current (GIRK) to ADO effects, APs were measured after the addition of DPCPX (selective A1R antagonist) or TPQ (selective GIRK blocker). KEY FINDINGS: A1R and GIRK mRNA expression were significantly increased in HF. In addition, ADO induced greater rate slowing and membrane hyperpolarization in HF vs CTL (p < 0.05). DPCPX prevented ADO-induced rate slowing in CTL and HF cells. The ADO-induced inward rectifying current, IKado, was observed significantly more frequently in HF than in CTL. TPQ prevented ADO-induced rate slowing in HF. SIGNIFICANCE: An increase in A1R and GIRK expression enhances IKAdo, causing hyperpolarization, and subsequent negative chronotropic effects in canine chronic HF at relevant [ADO]. GIRK blockade may be a useful strategy to mitigate bradycardia in HF.


Asunto(s)
Agonistas del Receptor de Adenosina A1/farmacología , Adenosina/farmacología , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/agonistas , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Receptor de Adenosina A1/metabolismo , Nodo Sinoatrial/citología , Nodo Sinoatrial/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Antagonistas del Receptor de Adenosina A1/farmacología , Animales , Venenos de Abeja/farmacología , Relojes Biológicos , Enfermedad Crónica , Perros , Femenino , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/antagonistas & inhibidores , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/efectos de los fármacos , Técnicas In Vitro , Masculino , Técnicas de Placa-Clamp , Bloqueadores de los Canales de Potasio/farmacología , Receptor de Adenosina A1/efectos de los fármacos , Xantinas/farmacología
4.
Toxicol Lett ; 318: 57-64, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31585160

RESUMEN

3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.


Asunto(s)
Antineoplásicos/toxicidad , Ventrículos Cardíacos/efectos de los fármacos , Insecticidas/toxicidad , Piruvatos/toxicidad , Rotenona/toxicidad , Taquicardia Ventricular/inducido químicamente , Fibrilación Ventricular/inducido químicamente , Remodelación Ventricular/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Cardiotoxicidad , Conexina 43/genética , Conexina 43/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/ultraestructura , Masculino , Canales de Potasio de Rectificación Interna/genética , Canales de Potasio de Rectificación Interna/metabolismo , Ratas Wistar , Periodo Refractario Electrofisiológico/efectos de los fármacos , Medición de Riesgo , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patología , Taquicardia Ventricular/fisiopatología , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/patología , Fibrilación Ventricular/fisiopatología
5.
Acta Cir Bras ; 34(9): e201900905, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31800679

RESUMEN

PURPOSE: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. METHODS: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. RESULTS: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. CONCLUSION: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Colecistectomía Laparoscópica/efectos adversos , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Dexmedetomidina/administración & dosificación , Isoxazoles/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , /tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Presión Arterial/efectos de los fármacos , Quimioterapia Combinada , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
6.
Mayo Clin Proc ; 94(12): 2476-2487, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31806101

RESUMEN

OBJECTIVE: To evaluate the effect of ß-blockers according to heart rate in patients with acute myocardial infarction (AMI) without heart failure (HF) or left ventricular systolic dysfunction (LVSD). PATIENTS AND METHODS: We enrolled patients with AMI without HF or LVSD between June 1, 2003, and February 28, 2015, from Seoul National University Hospital Acute Myocardial Infarction Registry. Patients were categorized according to discharge heart rate recorded on electrocardiographs and ß-blocker use. Low heart rate was defined as less than 75 beats/min. The primary end point was 5-year all-cause mortality according to discharge heart rate and ß-blocker use. RESULTS: Of 2271 patients, 1696 (74.7%) received ß-blockers and 1427 (62.8%) had low heart rates. At 5 years after discharge, 205 patients died. Overall, patients with low heart rates (P<.001) and those with ß-blocker treatment had lower mortality (P<.001). After adjustment for covariates, ß-blocker use was associated with 48% reduced risk for 5-year mortality in patients with high heart rates (hazard ratio, 0.52; 95% CI, 0.35-0.76), but not in those with low heart rates (P=.97). In an inverse-probability treatment-weighted cohort, ß-blocker use was also associated with improved mortality in those with a high heart rate. Findings were similar for 5-year cardiovascular mortality. CONCLUSION: Among survivors with AMI without HF or LVSD, ß-blocker use was associated with reduced 5-year all-cause mortality in patients who have high heart rates, but not in those with low heart rates.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Anciano , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológico , Tasa de Supervivencia , Disfunción Ventricular Izquierda
7.
Medicine (Baltimore) ; 98(50): e18331, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852127

RESUMEN

This study assessed sex differences in cardiac and motor functions, quality of life (QoL), and mental status in Chinese chronic heart failure (CHF) patients after metoprolol treatment.This single-center prospective study, conducted from February 2013 to April 2016, included CHF patients (men and women) with resting heart rate (HR) >80 beats/min using metoprolol continuous release tablets. Metoprolol-induced changes in cardiac and motor functions, QoL, and mental status at 1, 3, 6, 9, and 12 months from baseline, within and between the sexes, were analyzed. Descriptive data were represented as counts, percentages, and mean ± standard deviation. Differences at various follow-up periods were compared using repeated measures one-way analysis of variance, followed by post hoc Dunnett's multiple comparison test. Statistical significance was considered at P < .05.Compared with men, women reported significantly higher systolic blood pressure (SBP) (122.28 ±â€Š6.76 vs 125.47 ±â€Š6.67 mm Hg, P < .05) and Veterans Specific Activity Questionnaire score (8.16 ±â€Š0.98 vs 8.47 ±â€Š0.89, P = .05) at 12 months. Men reported higher Hospital Anxiety and Depression Scale scores for depression than women at 1 month (10.27 vs 8.83, P < .05) and for anxiety at 12 months (8.4 vs 7.72, P < .05). Metoprolol significantly decreased HR and Minnesota Living with Heart Failure Questionnaire score in men (64.5 ±â€Š3.13 and 53.7 ±â€Š8.00) and women (65.38 ±â€Š3.32 and 53.85 ±â€Š8.42, respectively). Ejection fraction (%, men: 50.00 ±â€Š4.45, women: 50.72 ±â€Š4.09), cardiac index (L/min/m, men: 2.70 ±â€Š0.25, women: 2.78 ±â€Š0.23), 6-minute walk test distance (m, men: 414.41 ±â€Š20.84, women: 420.34 ±â€Š20.35), and short form-8 questionnaire scores (men: 52.05 ±â€Š1.94, women: 52.19 ±â€Š2.58) increased significantly in both the sexes (P < .001 for all) at 12 months. Copenhagen Burnout Inventory score significantly increased in men (mean score 62.43, P < .05).Metoprolol treatment improves cardiac and motor functions, QoL, and anxiety scores but causes greater depression and burnout in men and women. Sex was seen to affect mental status of CHF patients the most.


Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/psicología , Metoprolol/uso terapéutico , Calidad de Vida , Factores Sexuales , Adulto , Anciano , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Grupo de Ascendencia Continental Asiática/psicología , China , Enfermedad Crónica , Depresión/tratamiento farmacológico , Depresión/etiología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
8.
Bratisl Lek Listy ; 120(12): 919-923, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31855051

RESUMEN

OBJECTIVE: The aim of the present study is to investigate the cardioprotective effect of lycopene, known for its antioxidant and anti-inflammatory effect, in a rat sepsis model induced by lypopolysaccharide (LPS). METHODS: The oxidative stress parameters, antioxidant parameters and cytokine levels with or without lycopene treatment in LPS­induced septic rats as well as in controls were measured in serum and tissue. Histologic examinations of the cardiac tissues were also performed. The Kruskal-Wallis and the Bonferroni-adjusted Mann-Whitney U Test was used for analysis. A p value < 0.05 was considered significant. RESULTS: The data of this study showed that lycopene pretreatment reduced the oxidative stres parametersand , proinflammatory cytokines as well as increased the antoxidant enzyme activities in both serum and cardiac tissues in LPS­induced septic rats.. Moreover, hyperaemia and haemorrhage in the epicardium, myocardium and endocardium were lower in the lycopene pretreated group as compared to the LPS alone group. CONCLUSION: These results suggest that lycopene could be beneficial for the prevention of cardiac injury caused by sepsis through reducing the cytokine levels and oxidative stress parameters (Tab. 4, Fig. 1, Ref. 35).


Asunto(s)
Antiinflamatorios/farmacología , Carotenoides/farmacología , Licopeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Choque Séptico/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Cardiotónicos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ratas
9.
Medicine (Baltimore) ; 98(51): e18311, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31860981

RESUMEN

BACKGROUND: Studies have shown the efficacy of norepinephrine in the treatment of maternal hypotension during cesarean section by comparing it to treatment with phenylephrine. However, few studies have compared the efficacy of norepinephrine to ephedrine. METHODS: Ninety-seven women undergoing elective cesarean section were administered norepinephrine at 4 µg/minute (group N; n = 48) or ephedrine at 4 mg/minute (group E; n = 49) immediately postspinal anesthesia, with an on-off titration to maintain systolic blood pressure (SBP) at 80% to 120% of baseline. A rescue bolus of 8 µg norepinephrine was given whenever SBP reached the predefined lower limit. Our primary outcome was the incidence of tachycardia. Secondary outcomes included the incidence of bradycardia, hypertension, hypotension, severe hypotension, hypotensive episodes, number of rescue top-ups, hemodynamic performance error including median performance error (MDPE), and median absolute performance error (MDAPE). Neonatal Apgar scores and umbilical arterial (UA) blood gas data were also collected. RESULTS: Women in group N experienced fewer cases of tachycardia (4.2% vs 30.6%, P = .002, odds ratio: 0.11 [95% confidence interval, CI: 0.02-0.47]), a lower standardized heart rate (HR) (70.3 ±â€Š11 vs 75 ±â€Š11, P = .04, difference: 4.7 ±â€Š2.2 [95% CI: 0.24-9.1]), and a lower MDPE for HR (1.3 ±â€Š9.6 vs 8.4 ±â€Š13.5 bpm, P = .003, difference: 3.1 ±â€Š1.8 [95% CI: -0.6-6.7]). In addition, the lowest or the highest HR was lower in group N compared to group E (both P < .05). Meanwhile, the standardized SBP in group N was lower than that in group E (P = .04). For neonates, the UA blood gas showed a higher base excess (BE) and a lower lactate level in group N compared to E (both P < .001). Other hemodynamic variables, maternal, and neonatal outcomes were similar. CONCLUSION: Infusion of 4 µg/minute norepinephrine presented fewer cases of tachycardia, less fluctuation and a lower HR compared to baseline values, as well as a less stressed fetal status compared to ephedrine infusion at 4 mg/minute. In addition, norepinephrine infusion presented a lower standardized SBP compared to ephedrine.


Asunto(s)
Anestesia Raquidea/métodos , Cesárea/efectos adversos , Efedrina/uso terapéutico , Hipotensión/prevención & control , Norepinefrina/uso terapéutico , Adulto , Anestesia Raquidea/efectos adversos , Presión Sanguínea/efectos de los fármacos , Cesárea/métodos , Método Doble Ciego , Efedrina/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipotensión/etiología , Infusiones Intravenosas , Norepinefrina/administración & dosificación , Embarazo
10.
J Med Life ; 12(3): 260-265, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31666828

RESUMEN

Lower back pain is one of the leading causes of disability in the world. The aim of this study was to evaluate the effect of supplementation of dexmedetomidine and neostigmine with lidocaine 1.5% and triamcinolone for epidural block in increasing the duration of analgesia among patients suffering from chronic low back pain. In this double-blind, randomized clinical trial, 33 patients with chronic low back pain were included in three groups of 11 patients for epidural blockage. Triamcinolone (40 mg/ml) was added to lidocaine 1.5% solution (2 cc/segment) for all three groups. In group N, neostigmine was used at a dose of 1 mg (mg), followed by group D (dexmedetomidine 35 µg [0.5 µg/kg]), and grou [ND (neostigmine 0.5 mg, and 35 µg dexmedetomidine, all of which were added to the triamcinolone and lidocaine solution in each group. Medications were injected into the epidural space using an interlaminar approach. Subsequently, scores of pain and duration of analgesia were recorded in questionnaires and analysed using SPSS version 23. One month after the injections, pain scores recorded in the N group were 7.6±1.4, followed by 5.88±1.2 in group D and 5.42 ±1.1 in group ND. Therefore, the pain scores were significantly higher in the neostigmine group than the other two groups (p = 0.02), but no significant difference was found between the two groups that received dexmedetomidine and a combination of dexmedetomidine + neostigmine. Three months after the injections, there was a significant difference in pain scores between the two groups (P = 0.01). Both neostigmine and dexmedetomidine were capable of reducing the pain of patients with chronic low back pain after epidural block. However, neostigmine's impact is lower compared to dexmedetomidine. The combination of the two drugs also reduced the pain scores of the patients after the intervention.


Asunto(s)
Analgesia Epidural , Dolor Crónico/tratamiento farmacológico , Dexmedetomidina/uso terapéutico , Lidocaína/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Neostigmina/uso terapéutico , Triamcinolona/uso terapéutico , Adulto , Presión Sanguínea/efectos de los fármacos , Dolor Crónico/fisiopatología , Dexmedetomidina/farmacología , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Lidocaína/farmacología , Dolor de la Región Lumbar/fisiopatología , Masculino , Neostigmina/farmacología , Oxígeno/metabolismo , Manejo del Dolor , Triamcinolona/farmacología
11.
BMC Neurol ; 19(1): 287, 2019 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-31729968

RESUMEN

BACKGROUND: Fingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA. Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h. Prior to 2014, FDO was undertaken only in clinics. As the FDO period is short, and fingolimod has accumulated evidence of a positive benefit:risk ratio, an in-home treatment-initiation program, Gilenya@Home, was developed to offer a convenient alternative. METHODS: Cardiac parameters and adverse events (AEs) were recorded by healthcare professionals performing fingolimod FDOs in the US Gilenya@Home program or in US Gilenya Assessment Network clinics. Anonymized data were collated retrospectively from the first 34 months in the home setting and from 78 months in clinics; data are reported descriptively. Satisfaction with Gilenya@Home was rated by patients using a 7-item questionnaire that considered aspects such as ease of scheduling, courtesy, and competency. RESULTS: Data were captured as part of standard care from 5573 patients initiating fingolimod in-home (October 2014 to July 2017) and from 15,025 patients initiating in-clinic (July 2010 to December 2016). In the Gilenya@Home questionnaire, 91.7% of 1848 respondents rated their overall satisfaction as "very good," and 7.6% rated their satisfaction as "good." AEs were reported for 30.7 and 32.6% of in-home and in-clinic patients, respectively. In total, 557 in-home (10.0%) and 398 in-clinic (2.6%) patients were monitored for > 6 h; 15 (0.3%) in-home and 129 (0.9%) in-clinic patients were transferred to an emergency room for overnight monitoring. The mean (standard deviation) heart rate (HR; bpm) pre-FDO was 74.8 (12.2) in-home and 74.2 (11.3) in-clinic; reduction in HR at 6 h postdose was 10.6 (12.0) and 6.3 (9.6), respectively. New-onset first-degree atrioventricular block was experienced by 132 (2.4%) in-home and 74 (0.5%) in-clinic patients, and Wenckebach (Mobitz type I) second-degree atrioventricular block by four (0.07%) and nine (0.1%) patients, with no cases of third-degree atrioventricular block. CONCLUSIONS: A substantial number of patients have initiated fingolimod at home, reporting very high levels of satisfaction. Gilenya@Home was as rigorous as the clinic setting in detecting cardiovascular events. Overall, FDO safety outcomes were similar with Gilenya@Home and in-clinic.


Asunto(s)
Bloqueo Atrioventricular/inducido químicamente , Clorhidrato de Fingolimod/efectos adversos , Servicios de Atención a Domicilio Provisto por Hospital , Inmunosupresores/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Bloqueo Atrioventricular/diagnóstico , Electroencefalografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Retrospectivos
12.
J Craniofac Surg ; 30(8): 2499-2501, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31567764

RESUMEN

PURPOSE: This study aimed to evaluate the suppressive effects of a small dose of butorphanol on sufentanil-induced cough during general anesthesia induction. METHODS: 120 patients who were scheduled for elective maxillofacial surgery of American Society of Anesthesiologists I∼II, aged 18∼65 years were randomly divided into 3 groups (n = 40). Patients received butorphanol 0.1 mg (group I), 1 mg (group II) or an equal volume of 0.9% normal saline (group III) 5 seconds right before sufentanil bolus (0.5ug/kg). Sufentanil was diluted into 5ug/mL and administrated within 5 seconds. The incidence and reflex degree of cough in all groups were evaluated within 2 minutes after the injection of sufentanil during anesthesia induction. Mean arterial pressure (MAP) and heart rate (HR) were recorded at T0 (before the injection of butorphanol or normal saline), T1 (before the injection of sufentanil) and T2 (2 minutes after sufentanil injection). RESULTS: The HR and MAP values were no significant difference among the 3 groups at the same observation point. In group II, the HR decreased significantly at T2 compared with T0 and T1 (P <0.05, T2 VS T0, T1). None of the patients in group I and group II had cough, and 33 patients in group III developed cough, of which 12.5% were mild, 40% were moderate, and 30% were severe. CONCLUSIONS: The results of present study suggest that a small dose of butorphanol 0.1 mg can prevent sufentanil-induced cough and ensure a relatively stable hemodynamic state during general anesthesia induction.


Asunto(s)
Butorfanol/uso terapéutico , Tos/prevención & control , Sufentanilo/efectos adversos , Adolescente , Adulto , Anciano , Anestesia General , Tos/inducido químicamente , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Reflejo , Adulto Joven
13.
High Blood Press Cardiovasc Prev ; 26(5): 405-411, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31625118

RESUMEN

INTRODUCTION: Prognostic significance of heart rate (HR) in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. AIM: To evaluate the association of HR and beta-blocker use with all-cause mortality and the optimal HR range in patients with HFpEF and sinus rhythm (SR). METHODS: During a follow-up of 2.7 years (IQR 1.2-4.1 years), the 330 patients with median age 73 (IQR 64-79) years, 52.1% men, were included. HFpEF was defined as patients with EF ≥ 50%. The outcome measure was all-cause mortality. RESULTS: In total, 96 (29.1%) of patients with HFpEF and SR died. A linear tendency between HR and mortality was observed in SR. Compared to the reference strata HR ≤ 60 bpm, HR increment was associated with progressively increased risk in mortality (Chi-square = 13.90, Log rank P = 0.001) by Kaplan-Meier analyses. Univariate Cox regression showed that in SR, compared with that in HR 61-80 bpm, the unadjusted hazard ratios for mortality were 0.41 (95% CI 0.23-0.74, P  = 0.003) in HR ≤ 60 bpm, 1.38 (95% CI 0.85-2.24, P  = 0.189) in HR > 80 bpm. Multivariate Cox regression showed that compared with that in HR 61-80 bpm, the adjusted hazard ratios for mortality were 0.37 (95% CI 0.19-0.75, P  =  0.005) in HR ≤ 60 bpm, 0.96 (95% CI 0.52-1.74, P  = 0.899) in HR > 80 bpm. Univariate Cox regression showed that the unadjusted hazard ratios for mortality were 0.52 (95% CI 0.33-0.84, P = 0.003) in patients with beta-blocker as compared patients without beta-blocker. Multivariate Cox regression showed that the adjusted hazard ratios for mortality were 0.48 (95% CI 0.26-0.87, P = 0.016) in patients with beta-blocker as compared patients without beta-blocker. CONCLUSIONS: HR is independently associated with increased all-cause mortality in SR and a lower HR (≤ 60 bpm) is favorable for better outcome in HFpEF patients with SR. Beta-blocker use is associated with reduced mortality and a lower HR is associated with reduced mortality in HFpEF patients with SR.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Endocrinology ; 160(12): 2787-2799, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31593246

RESUMEN

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/agonistas , Hiperandrogenismo/complicaciones , Liraglutida/uso terapéutico , Síndrome Metabólico/prevención & control , Síndrome del Ovario Poliquístico/complicaciones , Animales , Presión Sanguínea/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Resistencia a la Insulina , Leptina/sangre , Lípidos/sangre , Liraglutida/farmacología , Síndrome Metabólico/etiología , Posmenopausia , Distribución Aleatoria , Ratas Sprague-Dawley , Sistema Renina-Angiotensina/efectos de los fármacos
15.
Am J Vet Res ; 80(10): 912-922, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31556714

RESUMEN

OBJECTIVE: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS: 8 purpose-bred, 2-year-old Beagles. PROCEDURES: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 µg/kg) or MED mixed with 400 µg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 µg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Sistema Cardiovascular/efectos de los fármacos , Perros , Hipnóticos y Sedantes/farmacología , Imidazoles/farmacología , Medetomidina/farmacología , Quinolizinas/farmacología , Anestesia/veterinaria , Animales , Gasto Cardíaco/efectos de los fármacos , Estudios Cruzados , Dexmedetomidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Inyecciones Intramusculares/veterinaria , Masculino , Medetomidina/administración & dosificación , Medetomidina/antagonistas & inhibidores , Quinolizinas/antagonistas & inhibidores , Distribución Aleatoria , Método Simple Ciego
16.
Am J Vet Res ; 80(10): 969-975, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31556717

RESUMEN

OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs. ANIMALS: 6 healthy dogs. PROCEDURES: Injectable dexmedetomidine was administered IV (5 µg/kg) or via the OTM route (20 µg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry. RESULTS: For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.


Asunto(s)
Dexmedetomidina/farmacocinética , Perros/metabolismo , Hipnóticos y Sedantes/farmacocinética , Administración Intravenosa , Administración a través de la Mucosa , Administración Oral , Animales , Disponibilidad Biológica , Cromatografía Liquida , Estudios Cruzados , Dexmedetomidina/administración & dosificación , Femenino , Semivida , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/administración & dosificación , Infusiones Intravenosas , Masculino , Frecuencia Respiratoria/efectos de los fármacos
17.
J Anim Sci ; 97(11): 4496-4502, 2019 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-31504598

RESUMEN

Hazel leaves (Corylus avellana) fed to sheep resulted in decreased methane emissions without negatively affecting feed intake and were found to have antioxidant properties in vitro. The objective of this study was to evaluate effects of hazel leaves, rich in tannins, on blood antioxidant activity, cellular immune response, and heart beat parameters in sheep. Four experimental pellets were produced by mixing alfalfa and hazel leaves in different proportions, including alfalfa alone as a control, 30% and 60% of hazel leaves, the latter also with 3.8% polyethylene glycol (PEG). Six adult, nonpregnant, nonlactating female sheep (71 ± 5.7 kg of body weight) were allocated to 4 treatments in a 6 × 4 crossover design with four 18-d periods. The diet consisted of experimental pellets and ryegrass-dominated hay (ratio 80% to 20% in dry matter), resulting in hazel leaf proportions of approximately 0%, 25%, and 50% in the total diet. Blood samples were collected at the end of each period to determine plasma total phenol concentration and markers of oxidative status as well as peripheral blood mononuclear cells (PBMC) activation and proliferation response in vitro. Heart rate (HR) and HR variability parameters were measured for 2 consecutive days in each period, during different activities (i.e., eating pellets or hay, or lying). Treatments were compared with multiple comparisons and contrast analysis was used to test for linear and quadratic relations. Compared with control, feeding a high dosage of hazel leaves enhanced (P = 0.006) the plasma total antioxidant capacity, which linearly (P = 0.016) increased with increasing level of hazel leaves in the diet. The total phenol concentration and activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione reductase in the plasma were not different (P ≥ 0.23) among the treatments; however, the latter slightly increased linearly (P = 0.047) with increasing hazel leaves proportion. No differences were observed in the activation and proliferation of PBMC among treatments. The HR decreased linearly (P ≤ 0.009) during pellet eating and lying and the root mean square of successive differences of interbeat intervals (RMSSD) increased linearly (P = 0.037) when lying with increasing level of hazel leaves in the diet. In conclusion, our findings indicate that hazel leaves are a promising supplement to improve oxidative status with no effect on cellular immune response and cardiac stress level of sheep.


Asunto(s)
Antioxidantes/metabolismo , Corylus/química , Suplementos Dietéticos/análisis , Inmunidad Celular/efectos de los fármacos , Ovinos/fisiología , Alimentación Animal/análisis , Animales , Proliferación Celular , Dieta/veterinaria , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Lolium , Medicago sativa , Metano/metabolismo , Hojas de la Planta/química , Ovinos/sangre , Ovinos/inmunología , Taninos/metabolismo
18.
Undersea Hyperb Med ; 46(4): 483-494, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31509904

RESUMEN

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200±50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; andHBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.


Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Oxigenación Hiperbárica , Precondicionamiento Isquémico Miocárdico/métodos , Isquemia Miocárdica/terapia , Daño por Reperfusión Miocárdica/prevención & control , Bloqueadores de los Canales de Potasio/uso terapéutico , Amlodipino/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Terapia Combinada/métodos , Circulación Coronaria , Corazón , Frecuencia Cardíaca/efectos de los fármacos , Precondicionamiento Isquémico Miocárdico/efectos adversos , Peroxidación de Lípido , Masculino , Miocardio/patología , Nicorandil/uso terapéutico , Estrés Oxidativo , Ratas , Ratas Wistar , Recuperación de la Función , Verapamilo/uso terapéutico
19.
Vet J ; 251: 105346, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31492384

RESUMEN

The aim of this study was to compare the sedative and cardiovascular effects of dexmedetomidine (DEX) administrated via intranasal (IN) and intramuscular (IM) routes. This masked, randomised, crossover study used six male beagle dogs, receiving 0.02 mg/kg dexmedetomidine either IN (DEX-IN) or IM (DEX-IM), and an equal volume of saline by the alternative route. Dexmedetomidine plasma concentration was measured before (TB) and at time points (T) 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after drug administration (T0). Physiological variables, sedation scores and sedation times were recorded until recovery. Echocardiography was performed at TB and between T20-T40. Repeated data over time were analysed using a Scheirer-Ray-Hare test. Other data were compared using a Wilcoxon or Student's t test. Times from T0 to sternal position and from lateral to sternal position were longer for DEX-IN than DEX-IM (P = 0.018 and P = 0.009, respectively). Time from sternal to standing position was shorter for DEX-IN than DEX-IM (P = 0.03). Dexmedetomidine plasma concentrations were significantly lower for DEX-IN than DEX-IM from T10 to T120. Heart rate was significantly lower for DEX-IM than DEX-IN from T5 to T20. Echocardiography showed a decrease in systolic function and calculated cardiac output in DEX-IM as compared to baseline. The DEX concentration-sedation curve for DEX-IN as compared to DEX-IM was leftward shifted, whereas the IN and IM DEX concentration-variation-in-heart-rate curves overlapped. Although reaching lower plasma concentrations, IN dexmedetomidine produced similar sedation to IM dexmedetomidine without affecting cardiovascular function.


Asunto(s)
Administración Intranasal/veterinaria , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacocinética , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacocinética , Inyecciones Intramusculares/veterinaria , Animales , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Estudios Cruzados , Dexmedetomidina/sangre , Perros , Ecocardiografía/veterinaria , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Distribución Aleatoria
20.
Vet J ; 251: 105345, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31492389

RESUMEN

A constant rate infusion (CRI) of medetomidine is used to balance equine inhalation anesthesia, but its cardiovascular side effects are a concern. This experimental crossover study aimed to evaluate the effects of vatinoxan (a peripheral α2-adrenoceptor antagonist) on cardiorespiratory and gastrointestinal function in anesthetized healthy horses. Six horses received medetomidine hydrochloride 7µg/kg IV alone (MED) or with vatinoxan hydrochloride 140µg/kg IV (MED+V). Anesthesia was induced with midazolam and ketamine and maintained with isoflurane and medetomidine CRI for 60min. Heart rate, carotid and pulmonary arterial pressures, central venous pressure, cardiac output and arterial and mixed venous blood gases were measured. Selected cardiopulmonary parameters were calculated. Plasma drug concentrations were determined. Fecal output was measured over 24h. For statistical comparisons, repeated measures analysis of covariance and paired t-tests were applied. Heart rate decreased slightly from baseline in the MED group. Arterial blood pressures decreased with both treatments, but significantly more dobutamine was needed to maintain normotension with MED+V (P=0.018). Cardiac index (CI) and oxygen delivery index (DO2I) decreased significantly more with MED, with the largest difference observed at 20min: CI was 39±2 and 73±18 (P=0.009) and DO2I 7.4±1.2 and 15.3±4.8 (P=0.014)mL/min/kg with MED and MED+V, respectively. Fecal output or plasma concentrations of dexmedetomidine did not differ between the treatments. In conclusion, premedication with vatinoxan induced hypotension, thus its use in anesthetized horses warrants further studies. Even though heart rate and arterial blood pressures remained clinically acceptable with MED, cardiac performance and oxygen delivery were lower than with MED+V.


Asunto(s)
Motilidad Gastrointestinal/efectos de los fármacos , Isoflurano/farmacología , Medetomidina/farmacología , Quinolizinas/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2 , Anestesia por Inhalación/veterinaria , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Fenómenos Fisiológicos Cardiovasculares/efectos de los fármacos , Estudios Cruzados , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Caballos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Isoflurano/administración & dosificación , Masculino , Medetomidina/administración & dosificación , Quinolizinas/sangre , Quinolizinas/farmacocinética
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