O presente estudo objetivou avaliar o efeito da dexmedetomidina, associada ou não à bupivacaína, na raquianestesia de fêmeas felinas submetidas à ovariohisterectomia. Foram utilizadas 34 gatas, jovens e adultas, sem raça definida, saudáveis submetidas a anestesia inalatória com isofluorano e aos seguintes tratamentos, após distribuição aleatória: grupo bupivacaína (GB) - raquianestesia com a bupivacaína isolada (0,5 mg/kg), grupo dexmedetomidina (GD) - raquianestesia com dexmedetomidina (1 mcg/kg) e grupo de dexmedetomidina bupivacaína (GDB) - raquianestesia com dexmedetomidina (1 mcg/kg) e bupivacaína (0,5 mg/kg). Após a indução da anestesia e manutenção com isofluorano, os animais foram posicionados em decúbito lateral direito para punção subaracnoide realizada no espaço lombossacro com agulha espinhal 25G. Os animais foram mantidos em decúbito dorsal até o final do procedimento cirúrgico e os atributos fisiológicos foram avaliados no período pré, trans e por 3 horas no período pós-operatório. Nenhum animal apresentou arritmia ou hipotensão arterial. O GDB apresentou redução significativa da frequência cardíaca e incremento pressórico quando comparado ao GB (p<0,01). Não houve diferença significativa no consumo de fentanil e no requerimento de isofluorano entre os grupos durante o procedimento cirúrgico. Na dose e diluição empregadas, a bupivacaína não determinou bloqueio motor significativo. As associações utilizadas promoveram analgesia adequada no período pós-operatório. O GDB apresentou maior grau de sedação durante parte da recuperação da anestesia (90min) (p<0,05), sem aumento no tempo de extubação. A adição da dexmedetomidina à bupivacaína na raquianestesia não aumentou o bloqueio motor e sensitivo; entretanto aumentou o grau de sedação dos animais promovendo melhor qualidade na recuperação anestésica sem deflagrar complicações cardiorrespiratória ou neurológica. / The present study aimed to evaluate the effect of dexmedetomidine, associated or not to bupivacaine, on spinal anesthesia in female felines submitted to ovariohysterectomy. Thirty four mixed breed healthy cats, young and adult, underwent inhalation anesthesia with isoflurane and the following treatments, after random distribution: bupivacaine group (BG) - spinal anesthesia with bupivacaine alone (0.5 mg/kg), dexmedetomidine group (DG) - spinal anesthesia with dexmedetomidine (1 mcg/kg). and dexmedetomidine/bupivacaine group (DBG) - spinal anesthesia with dexmedetomidine (1 mcg/kg) and bupivacaine (0.5 mg/kg). After anesthetic induction and maintenance with isoflurane, the animals were positioned in the right lateral recumbency for subarachnoid puncture performed in the lumbosacral space with a 25G spinal needle. The animals were kept in dorsal recumbency until the end of the surgical procedure and the physiological parameters were assessed in the pre, trans and 3 hours postoperative period. No animal presented arrhythmia or arterial hypotension. DBG presented a significant reduction in heart rate and pressure increase when compared to BG (p <0.01). There was no significant difference in fentanyl consumption and in the isoflurane requirement between groups during the surgical procedure. At the dose and dilution used, bupivacaine did not determine significant motor blockage. The associations used promoted adequate analgesia in the postoperative period. DBG had a higher degree of sedation during part of the anesthetic recovery (90min) (p <0.05), without an increase in extubation time. The addition of dexmedetomidine to bupivacaine in spinal anesthesia did not increase motor and sensory blockage; however, it increased the sedation level of the animals, promoting better quality of anesthetic recovery without triggering cardiorespiratory or neurological complications.

Exercise Induced Bronchoconstriction (EIB) is common amongst elite athletes. Short-acting β2-agonists represent the first-line treatment of EIB, however; limited data currently exists examining the ergogenic and pharmacokinetic impact of chronic short-acting β2-agonist administration. Furthermore, the ergogenic impact of acute and chronic administration of short-acting β2-agonists in asthmatic individuals is unknown. Whilst the short-acting β2-agonist salbutamol is permitted in and out of competition due to a known pharmacokinetic response, no urinary threshold has been established for the use of the alternative short-acting β2-agonist terbutaline. The purpose of study 1 was to investigate the ergogenic potential of the WADA upper daily limit of 1600 μg·day-1 salbutamol every day for 6 weeks versus placebo, alongside combined resistance and endurance training. Findings highlighted improvements in; 1 repetition maximum (1RM) bench press (Baseline: 65.6 ± 5.4 kg vs. 64.3 ± 4.9 kg – 6 weeks: 70.3 ± 4.9 vs. 72.5 ± 5.4 kg) and leg press (Baseline: 250 ± 26.9 vs. 217.9 ± 19 kg – 6 weeks: 282.5 ± 22.5 vs. 282.8 ± 18.3 kg); vertical jump test (Baseline: 53.5 ± 4.1 vs. 50.4 ± 2.1 cm – 6 weeks: 55 ± 3.5 vs. 52.4 ± 1.7 cm); 3 km running time-trial performance (Baseline: 988.7 ± 68.7 vs. 1040.5 ± 66.3 s – 6 weeks: 947.5 ± 54.9 vs. 1004.3 ± 70.5 s); isokinetic dynamometry (Baseline: 196.1 ± 47.3 vs. 184.6 ± 35.0 n.m. – 6 weeks: 179.5 ± 48.9 vs. 195.2 ± 28.9 n.m.); and body composition (Baseline: 32.1 ± 13.9 vs. 34.9 ± 10.4 mm – 6 weeks: 32.4 ± 14.5 vs. 34.5 ± 10 mm) for both the salbutamol group and the placebo group, respectively, over the 6 week period, with no difference observed between groups, indicating long-term therapeutic use of salbutamol at the WADA upper daily limit has no ergogenic effect. Of note, one participant exceeded the urinary threshold, presenting with an adverse 3 | P a g e analytical finding (AAF) showing that the upper daily limit can lead to AAF’s in susceptible individuals. Athletes who respond poorly to salbutamol treatment are able to apply for the use of the short-acting β2-agonist terbutaline via a therapeutic use exemption (TUE) certificate. Urinary upper limits are unknown for terbutaline and as such it is prohibited at all times without the presentation of a TUE. The purpose of study 2 was to investigate the urinary excretion of terbutaline following single and repeated use of inhaled or oral terbutaline. The aim of the study was to establish a differential distinction between routes of administration which could assist the WADA with regard to anti-doping policy and procedure. Results demonstrated a significant difference in urine concentration of terbutaline between inhaled and oral administration for female Caucasian (670.1 ± 128.3 vs. 361.8 ± 43.8 ng·ml-1; P=0.019; 680.8 ± 91 vs. 369.9 ± 41.9 ng·ml-1; P=0.006), male Afro-Caribbean (343.18 ± 45 vs. 231.3 ± 32.95 ng·ml-1; P=0.044; 389.73 ± 67.4 vs. 212.4 ± 50.3 ng·ml-1; P=0.008) and male Asian (266.4 ± 23.7 vs. 143.3 ± 22 ng·ml-1; P=0.004; 379.5 ± 50.4 vs. 197.5 ± 38.6 ng·ml-1; P=0.000) groups for single (5 mg oral vs. 2 mg inhaled) and repeated (4 x 5 mg oral vs. 8 x 1 mg inhaled) administration trials, respectively. No difference was observed in male Caucasians. High intra- and inter-individual variability between samples meant that a clear distinction between routes of administration could not be established. The study was able to identify an upper urinary threshold following inhaled administration of 1284.3 ng·ml-1 and an upper urinary threshold following oral use of 2376.3 ng·ml-1 which may inform the process of distinguishing between inhaled and oral use. Athletes are permitted to use inhaled terbutaline therapeutically through the TUE process. The purpose of study 3 was to investigate the ergogenic effect of terbutaline at high (2 mg and 4 mg) therapeutic inhaled doses on 3 km running time-trial performance in males and females. The 4 | P a g e study found that inhaled terbutaline, when used at the highest therapeutic dose, has no impact upon 3 km time-trial performance in males (956.3 s vs. 982 s) and females (1249 s vs. 1214.7 s) for placebo vs. 4 mg inhaled terbutaline, respectively. The majority of studies investigating the ergogenic potential of salbutamol have been in healthy individuals. It is not yet understood whether the exercise response differs in asthmatic individuals. The purpose of study 4 was to investigate the use of inhaled salbutamol (400 μg) during a 3 km running time-trial in eucapnic voluntary hyperpnoea positive (EVH+ve) and negative (EVH-ve) individuals, in a low humidity environment. Results demonstrated increased FEV1 in both groups following salbutamol inhalation, which did not translate to improved performance. No performance differences were found between salbutamol and placebo (Sal: 1012.7 ± 50 vs. 962.1 ± 37.5 s – Pla: 1002.4 ± 46.5 vs. 962 ± 28.8 s) in the EVH+ve group vs. the EVH-ve group, respectively. This thesis is the first to investigate the effects of long-term use of salbutamol at the WADA upper daily limit on exercise performance. It is also the first study to establish upper urinary thresholds for terbutaline use, and the effects of therapeutic inhaled terbutaline on exercise performance. The effect of salbutamol on exercise performance at low humidity in asthmatic individuals has also never previously been investigated. Overall, the findings from this thesis support previous research that inhaled β2-agonist use does not provide any ergogenic potential. With β2-agonists being an essential therapy for the treatment of EIB their current position on the WADA List of Prohibited Substances and Methods is appropriate. Further research is warranted to fully elucidate the upper urinary threshold for terbutaline to inform WADA and support the re-introduction of terbutaline as a therapeutic tool in the treatment of EIB in athletes.

Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-10Bitstream added on 2014-06-13T19:09:54Z : No. of bitstreams: 1 silva_gb_me_jabo.pdf: 1117997 bytes, checksum: 88ee7014b706d275943b075b58aba825 (MD5) / A medula espinhal tem importante papel no mecanismo de transmissão dos impulsos nervosos nociceptivos. O bloqueio desses impulsos interrompe ou minimiza a dor derivada da liberação de mediadores inflamatórios deletérios ao organismo. Assim ela tem sido sede de administração de fármacos, tanto para a realização de bloqueios anestésicos, quanto para a prevenção da dor pós-operatória. Em éguas é comum a indicação do uso da via peridural caudal para a administração de fármacos como nos casos de prolapsos uterinos e vaginais, lacerações vulvo-perineais decorrentes de distocias ou de monta natural, nos casos de pneumovagina e torções uterinas. Avaliou-se 3 grupos com 7 éguas cada, após receberem injeção peridural de 0,25 mg/kg de lidocaína associada com solução de cloreto de sódio 0,9% (GLS) ou lidocaína, na mesma dose, associada à 0,17 mg/kg de xilazina (GLX) ou 0,02 mg/kg detomidina (GLD). A avaliação considerou o perfil clínico por meio da aferição das frequências cardíaca (FC) e respiratória (f), da pressão arterial média (PA) e da avaliação da sensibilidade cutânea (SCP) com o uso de filamentos de von Frey em éguas submetidas a incisões cutâneas na região glútea. Em decorrência da diminuição da sensibilidade cutânea promovida pelos tratamentos, os valores de FC, f e de PA mantiveram-se estáveis, com pequeno declínio nos grupos GLX e GLD. As associações de lidocaína com xilazina ou com detomidina (GLX e GLD) diminuíram significativamente a sensibilidade cutânea pós-incisional (SCP) logo a partir de T15, quando comparadas ao grupo que recebeu apenas lidocaína associada á solução de cloreto de sódio 0,9% (GLS). Os três grupos apresentaram diminuíção significativa da SCP em todos os tempos após as aplicações quando comparados ao T0... / The spinal cord plays an important role the mechanism of tranmission of nociceptive nerve impulses. Blocking these impulses stop or minimize the pain derived from the release of inflammatory mediators deleterious to the body. So it has been the seat of administration of drugs, both the anesthetic blocks, and for the prevention of postoperative pain. In mares is common to indicate the use of epidural caudal to the administration of drugs as in cases of uterine prolapse and vaginal, vulvo-perineal lacerations resulting from dystocias natural mating or in cases of uterine pneumovagina and twists. We evaluated 3 groups of 7 mares each, after receiving epidural injection of 0.25 mg/kg of lidocaine mixed with sodium chloride 0.9% (GLS) or lidocaine, the same dose associated with 0.17 mg/kg xylazine (GLX) or 0.02 mg/kg detomidine (GLD). The evaluation considered the clinical profile through measurement of heart rate (HR) and respiratory rate (RR), mean arterial pressure (BP) and the evaluation of skin sensitivity (PCS) using von Frey filaments in mares undergoing skin incisions in the gluteal region. Due to the decrease in skin sensitivity promoted by the treatments, the values of FC, fe, BP remained stable, with small decline in GLD and GLX groups. Combinations of lidocaine and xylazine or detomidine (GLD and GLX) significantly decreased the sensitivity of the skin post-incision (SCP) as early as T15, compared with the group receiving only lidocaine associated with the solution of sodium chloride 0.9% (GLS). The three groups showed a significant decrease in SCP at all times after the applications when compared to T0. The GLS group showed significant differences between the values of the sides and incised not incised in the times T45 to T105, the GLX group from T60 to T1440 (except T75), and the GLD group from T90 to T1440... (Complete abstract click electronic access below)

Submitted by SAMUEL DOS SANTOS SOUSA null (samuerr@hotmail.com) on 2016-11-25T13:56:01Z No. of bitstreams: 1 DOC. FINAL - DISSERTAÇÃO.pdf: 1281598 bytes, checksum: da30a95bebfc6a71081a5f812835a040 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-11-29T13:18:47Z (GMT) No. of bitstreams: 1 sousa_ss_me_jabo.pdf: 1281598 bytes, checksum: da30a95bebfc6a71081a5f812835a040 (MD5) / Made available in DSpace on 2016-11-29T13:18:47Z (GMT). No. of bitstreams: 1 sousa_ss_me_jabo.pdf: 1281598 bytes, checksum: da30a95bebfc6a71081a5f812835a040 (MD5) Previous issue date: 2016-08-18 / Existem poucos protocolos para a contenção e sedação de jumentos . Os agonistas alfa-2 são os fármacos mais amplamente administrados e é sabido que essa classe de fármacos pode produzir alguns efeitos deletérios no sistema cardiorrespiratório do animal. Os fármacos da classe dos opioides vêem ganhando espaço na prática anestésica com asininos, pois esses fármacos são utilizados como uma alternativa para a sedação desses animais. Além de produzirem certo grau de sedação, possuem característica analgésica, sem promover efeitos adversos. Na literatura pesquisada não foi encontrado, nenhum estudo sobre o uso associado de xilazina em infusão contínua com meperidina e seus efeitos hemodinâmicos nos muares. Diante deste exposto, objetivou-se estudar os efeitos da associação da infusão contínua da xilazina com bollus intramuscular de meperidina como protocolo de sedação em jumentos. Para tal, foram utilizados seis jumentos, SRD, sendo um macho e cinco fêmeas, com peso médio de 141±23 kg. Os animais foram submetidos a três protocolos experimentais dividos em três grupos, Grupo A: infusão contínua intravenosa de 1,1 mg/kg/hora de xilazina a solução salina por via intramuscular; Grupo B: infusão contínua intravenosa de 0,8 mg/kg/hora de xilazina e solução salina por via intramuscular e Grupo C: infusão contínua intravenosa de 0,8 mg/kg/hora de xilazina e 4 mg/kg de meperidina por via intramuscular. Foi observado redução na frequência respiratória, pressão arterial sistólica nos animais do grupo A e C, diminuição da pressão arterial diastólica e média em todos os grupos. Foi observada redução na altura da cabeça em todos os grupos. A associação da meperidina com xilazina em infusão contínua não provocou alterações cardiorrespiratórias significativas e produziu grau de sedação satisfatório / To the present, there has been few descriptions of anesthetic protocol for restraint and sedation in donkey (Equus asinus). Alpha-2-agonists are widely administered class of drugs. Known to produce some deleterious effects over the cardiopulmonary system. The use of opioids in donkeys has sained popularity anesthetic practicioners, since these drugs are used as an alternative sedative with analgesic characteristics with minimal side effects. To our knowledge, there has not been study evaluating the effects of the association of continuous rate infusion of xilazine with meperidine given intramuscularly over the cardiovascular parameters of donkeys. Therefore, the objective of our study evaluate was to the capacity of sedation and the cardiorespiratory implications of the anesthetic association in donkeys. In order to performe the study, six mixed breed, one male and five females, were used. The average weight has 141 ± 23 kg. The animals were subjected to three experimental protocols. Group A: Continuous intravenous infusion of 1.1 mg / kg / hour of xylazine and saline solution intramuscularly; Group B: Continuous intravenous infusion of 0.8 mg / kg / hour of xylazine and saline solution intramuscularly and Group C: continuous intravenous infusion of 0.8 mg / kg / hour of xylazine and 4 mg / kg of meperidine intramuscularly. Respiratory rate and systolic blood pressure decreased in animals of group A and C. While diastolic blood pressure and mean arterial pressure decreased in all three groups. Head Height lowered following treatment in all groups. The combination of meperidine with continuous rate infusion of xylazine did not cause significant cardiorespiratory implications and produced satisfactory degree of sedation.

Made available in DSpace on 2016-01-26T18:55:33Z (GMT). No. of bitstreams: 1 dissertacao.pdf: 1231508 bytes, checksum: 25c34b6cb3fd325bb34877b212f30d24 (MD5) Previous issue date: 2011-09-29 / This study aimed to evaluate the sedative, antinociceptive and cardiopulmonary effects of detomidine alone and in combination with morphine or methadone to the oral cavity approach. Six adult mares were evaluated using a crossover design with at least 7 days between treatments. All the horses were medicated with detomidine (20µg/kg, IV), detomidine (10µg/kg, IV) in combination with morphine (0,1mg/kg, IV) or methadone (0,1mg/kg, IV). Behaviors alteration, sedation degree, oral cavity sensibility, muscle tone of tongue, heart rate, mean arterial blood pressure, arterial blood gases were investigated during 120 minutes. The parametric data were analyzed with ANOVA and Tukey s test, and non parametric data were analyzed with Kruskall-Wallis and Fridman s test with post-Dunn test (P<0,05). In all the treatment groups, the maximum sedative effect was observed between 5 and 60 minutes after drugs administration. The must sedative effect was observed in detomidine horses treated. Respiratory stability was observed in all the groups, with more pronounced cardiovascular changes in DET group. It was concluded that all treatments were satisfactory for oral cavity approach. However, the combination of opioids did not potentiate the sedative effect and, neither increased or prolonged the antinoceptive effect mediate by detomidine. / Objetivou-se avaliar os efeitos sedativos, antinociceptivos e cardiorrespiratórios da administração da detomidina isolada e associada à morfina e metadona para abordagem da cavidade oral de equinos em posição quadrupedal. Foram avaliadas seis éguas, mestiças, adultas, com peso médio de 428±42kg, que foram distribuídas em delineamento de quadrado latino. Cada um dos animais foi tratado com intervalo mínimo de sete dias entre cada avaliação, sendo submetidos aos protocolos de sedação com detomidina (20&#61549;g/kg, IV) (DET), detomidina (10&#61549;g/kg, IV) associada a 0,1mg/kg (IV) de morfina (MORF) e detomidina (10&#61549;g/kg IV) associada a 0,1mg/kg (IV) de metadona (MET). Foram avaliados, através do sistema de escore durante 120 minutos: alteração comportamental, grau de sedação, sensibilidade da cavidade oral, tônus da língua, frequência cardíaca, pressão arterial média, frequência respiratória e variáveis hemogasométricas. A estatística foi realizada com análise de variância, teste de Tukey e análise de medidas repetidas, para as variáveis paramétricas. Para as variáveis não paramétricas foram empregados os testes de Kruskall-Wallis e de Friedmanm com contrastes pelo método de Dunn (P<0,05). O efeito sedativo foi predominante entre 5 e 60 minutos após a administração dos fármacos, em todos os grupos, sendo mais pronunciado no grupo DET. A sensibilidade da cavidade oral e o tônus da língua não diferiram entre os tratamentos. Estabilidade respiratória foi observada em todos os tratamentos, com alterações cardiovasculares mais pronunciadas no grupo DET. Conclui-se que os três tratamentos permitiram a abordagem da cavidade oral, no entanto a associação dos opioides não potencializou o efeito sedativo, bem como não incrementou ou prolongou o efeito antinociceptivo mediado pela detomidina.

Made available in DSpace on 2016-07-18T17:53:09Z (GMT). No. of bitstreams: 1 dissertacao.pdf: 1231508 bytes, checksum: 25c34b6cb3fd325bb34877b212f30d24 (MD5) Previous issue date: 2011-09-29 / This study aimed to evaluate the sedative, antinociceptive and cardiopulmonary effects of detomidine alone and in combination with morphine or methadone to the oral cavity approach. Six adult mares were evaluated using a crossover design with at least 7 days between treatments. All the horses were medicated with detomidine (20µg/kg, IV), detomidine (10µg/kg, IV) in combination with morphine (0,1mg/kg, IV) or methadone (0,1mg/kg, IV). Behaviors alteration, sedation degree, oral cavity sensibility, muscle tone of tongue, heart rate, mean arterial blood pressure, arterial blood gases were investigated during 120 minutes. The parametric data were analyzed with ANOVA and Tukey s test, and non parametric data were analyzed with Kruskall-Wallis and Fridman s test with post-Dunn test (P<0,05). In all the treatment groups, the maximum sedative effect was observed between 5 and 60 minutes after drugs administration. The must sedative effect was observed in detomidine horses treated. Respiratory stability was observed in all the groups, with more pronounced cardiovascular changes in DET group. It was concluded that all treatments were satisfactory for oral cavity approach. However, the combination of opioids did not potentiate the sedative effect and, neither increased or prolonged the antinoceptive effect mediate by detomidine. / Objetivou-se avaliar os efeitos sedativos, antinociceptivos e cardiorrespiratórios da administração da detomidina isolada e associada à morfina e metadona para abordagem da cavidade oral de equinos em posição quadrupedal. Foram avaliadas seis éguas, mestiças, adultas, com peso médio de 428±42kg, que foram distribuídas em delineamento de quadrado latino. Cada um dos animais foi tratado com intervalo mínimo de sete dias entre cada avaliação, sendo submetidos aos protocolos de sedação com detomidina (20&#61549;g/kg, IV) (DET), detomidina (10&#61549;g/kg, IV) associada a 0,1mg/kg (IV) de morfina (MORF) e detomidina (10&#61549;g/kg IV) associada a 0,1mg/kg (IV) de metadona (MET). Foram avaliados, através do sistema de escore durante 120 minutos: alteração comportamental, grau de sedação, sensibilidade da cavidade oral, tônus da língua, frequência cardíaca, pressão arterial média, frequência respiratória e variáveis hemogasométricas. A estatística foi realizada com análise de variância, teste de Tukey e análise de medidas repetidas, para as variáveis paramétricas. Para as variáveis não paramétricas foram empregados os testes de Kruskall-Wallis e de Friedmanm com contrastes pelo método de Dunn (P<0,05). O efeito sedativo foi predominante entre 5 e 60 minutos após a administração dos fármacos, em todos os grupos, sendo mais pronunciado no grupo DET. A sensibilidade da cavidade oral e o tônus da língua não diferiram entre os tratamentos. Estabilidade respiratória foi observada em todos os tratamentos, com alterações cardiovasculares mais pronunciadas no grupo DET. Conclui-se que os três tratamentos permitiram a abordagem da cavidade oral, no entanto a associação dos opioides não potencializou o efeito sedativo, bem como não incrementou ou prolongou o efeito antinociceptivo mediado pela detomidina.

Previous studies with pharmacopuncture in dogs showed its advantage for sedation, minimizing undesirable effects. The use of pharmocopuncture with xylazine in Yin Tang acupoint of dogs is investigated. Eight dogs were randomly submitted to four different treatment protocols according to a Latin Square double blind design: 1) 0.01 mL/kg of saline injected into Yin Tang acupoint (aquapuncture), 2) 1 mg/kg of xylazine injected subcutaneously at the dorsal region, 3) 0.2 mg/kg of xylazine injected subcutaneously at the dorsal region and 4) 0.2 mg/kg of xylazine injected into Yin-Tang acupoint (pharmacopuncture). Rectal temperature, heart and respiratory rates, arterial blood pressure, oxygen hemoglobin saturation and pulse rate and degree of sedation were measured before and at 5, 10, 30, 40, 50 and 60 minutes after treatments. Sedation was observed in xylazine and pharmacopuncture groups while saline injection and sub -dose of xylazine did not induce sedation. Both xylazine and pharmacopuncture induced reduction in respiratory rate, heart rate and arterial blood pressure. In conclusion, pharmacopuncture and the conventional dose of xylazine produced similar sedation in dogs. The results indicate the potential application of pharmacopuncture in dogs. Further studies could elucidate the optimal doses, drugs and acupoints to achieve the best effect. / Acupuntura é uma técnica terapêutica milenar reconhecida pela OMS (Organização Mundial de Saúde) que consiste na inserção de agulhas em pontos específicos do corpo. A farmacopuntura é uma importante área da acupuntura que consiste no uso de fármacos injetados em acupontos para potencializar seus efeitos. Um exemplo é o uso de sedativos como a Xilazina, uma droga agonista a2- adrenérgico, muito utilizada na rotina clínica em animais, que promove sedação, analgesia e miorrelaxamento dose-dependentes. O trabalho objetivou investigar o efeito sedativo da farmacopuntura com xilazina, bem como da aquapuntura no acuponto Yin tang em cães, além de verificar se este efeito é suficiente para realização de pequenos procedimentos clínicos e cirúrgicos. O experimento consistiu em quatro tratamentos (T1: controle da droga (Xilazina 1mg/kg) (Xil), T2: controle da subdose (0,01mL/kg Xilazina no subcutâneo) (1/5 Xil s.c), T3: controle do estímulo mecânico do ponto (0,01mL/kg solução salina no Yin tang) (AquaAP), T4: teste (Xilazina 0,2mg/kg no Yin tang) (FarmacoAP), em oito cadelas, distribuídas em um quadrado latino com intervalos de sete dias, de forma que todos os animais passaram pelos tratamentos. O grupo FarmacoAP apresentou efeito sedativo semelhante ao grupo controle Xil, porém a duração deste foi menor, demonstrando que a farmacopuntura funcionou e potencializou o efeito da droga. / Mestre em Ciências Veterinárias

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2015-02-03T09:34:31Z No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-02-05T13:09:32Z (GMT) No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-05T13:09:32Z (GMT). No. of bitstreams: 2 Dissertacao - Sandro de Melo Braga - 2014.pdf: 4351893 bytes, checksum: abf7d37b6f843e30fee499929c15eb91 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-07-15 / Agonist drugs α-2 adrenergic receptors are used in veterinary medicine to promote sedation, analgesia and muscle relaxation. In horses with xylazine and detomidine are used in preanesthetic medication such as sedatives for procedures or surgeries in the standing position with the aid of locoregional anesthesia in analgesic infusions associated with general anesthesia for invasive procedures, or associated with dissociative drugs to anesthesia Overall the equine field. In the first study aimed to evaluate the sedative, gastrointestinal, cardiovascular and blood gas of xylazine and detomidine administered at different doses in horses effects. Eight horses, four males and four females, aged between five and 15 years, weighing 276.58±9.23 kg were used. The experimental design was randomized crossover using animals of six different occasions to receive: xylazine 0.5 mg/kg (X05), 1.0 mg/kg (X1), 1.5 mg/kg (X15); 20μg/kg detomidine (D20), 40 mg/kg (D40) and 60μg/kg (D60). The parameters evaluated were heart rate (HR); the electrocardiogram (ECG); respiratory frequency (f); systolic blood pressure (SBP), diastolic (DBP) and mean (MAP) by invasive method; Sedation (RAC); rectal temperature (T); intestinal motility (MI); blood gases and electrolytes. Some showed similar results to those previously reported with xylazine and detomidine as good sedation, significant reduction of HR and f, however, there was an increase in BP lasting with increasing dose of detomidine, as well as a reduction in intestinal motility for periods there are 180 minutes with the same drug. In the review of blood gas analysis showed a decrease in PaO 2 and increase in PaCO 2 in arterial blood, indicative of respiratory depression, increased bicarbonate ion (HCO 3 -) and base excess, however they remained within normal limits for the species. It follows that promotes more efficient detomidine sedation, however promotes a greater depression in cardiac system and intestinal motility compared with xylazine in horses. In the second study aimed to evaluate the sedative, cardiovascular and echodopplercardiographic effects of xylazine and detomidine in horses. Six horses, two males and four females, aged between five and 15 years, weighing 276.58 ± 9.23 kg were used . The animals used in randomized crossover design twice for receiving xylazine 1.0 mg/kg (GX) detomidine or 40 µg/kg (GD), administered intravenously. In addition to the parameters evaluated in the first phase of the study, also cardiac output (CO), cardiac index (CI), aortic diameter (AD), ejection fraction (FE) and fractional shortening (FS) by echocardiography were recorded. The results showed intense cardiorespiratory depression in animals that received detomidine, however with greater sedative effects compared to xylazine group. BP values showed an initial increase only in the detomidine group, lasting approximately 30 minutes and subsequent reduction of the values, without characterizing hypertension and hypotension. In echodopplercardiographic evaluation, the GD had major depression in ventricular function parameters, for the group GX and this review was efficient compared with values obtained in other studies by methods already established. It is concluded that detomidine sedation promotes more efficient compared to xylazine in horses, however the depressive effects on cardiovascular variables are evaluated by echocardiogram greatest method. / Em equinos a xilazina e a detomidina são utilizadas na medicação pré-anestésica, como sedativos para procedimentos ou cirurgias em posição quadrupedal com o auxílio de anestesia locorregional, em infusões analgésicas associadas à anestesia geral para procedimentos invasivos, ou associadas a fármacos dissociativos na manutenção da anestesia geral a campo. No primeiro estudo objetivou-se avaliar os efeitos sedativos, gastrointestinais, cardiovasculares e hemogasométricos da xilazina e da detomidina administradas em diferentes doses em equinos. Foram utilizados oito equinos, quatro machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. O delineamento foi cruzado aleatório, utilizando os animais em seis ocasiões diferentes para receberem: xilazina 0,5 mg/kg (X05), 1,0 mg/kg (X1), 1,5 mg/kg (X15), detomidina 20 µg/kg (D20), 40 µg/kg (D40) e 60 µg/kg (D60). Os parâmetros avaliados foram frequência cardíaca (FC); traçado eletrocardiográfico (ECG); frequência respiratória (f); pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) pelo método invasivo; grau de sedação (SD); temperatura retal (T); motilidade intestinal (MI); gases sanguíneos e eletrólitos. Foram obtidos resultados similares aos descritos na literatura com xilazina e detomidina, como boa sedação, redução significativa da FC e f, no entanto, observou-se aumento duradouro da PA com o incremento da dose de detomidina, assim como redução na motilidade intestinal por períodos superiores a 180 minutos, com o mesmo fármaco. Houve redução da PaO 2 e aumento da PaCO 2 e do bicarbonato(HCO3) -com déficit de base. No entanto os valores permaneceram dentro dos limites de normalidade para a espécie. Concluiu-se que a detomidina promove sedação mais eficiente, no entanto induz maior depressão cardiorrespiratória e da motilidade intestinal, quando comparada à xilazina em equinos. No segundo ensaio objetivou-se avaliar os efeitos sedativos, cardiovasculares e ecodopplercardiográficos da xilazina e da detomidina em equinos. Foram utilizados seis equinos, dois machos e quatro fêmeas, com idade entre cinco e 15 anos, pesando 276,58 ± 9,23 kg. Os animais foram usados em delineamento cruzado aleatório, para receberem xilazina, 1,0 mg/kg (GX) ou detomidina 40 µg/kg (GD), pela via endovenosa. Além dos parâmetros avaliados na primeira fase do estudo, também foram registrados débito cardíaco (DC), índice cardíaco (IC), diâmetro da aorta (DA), fração de ejeção (FE) e fração de encurtamento (FS), por ecodopplercardiografia. Houve depressão cardiorrespiratória e efeito sedativo mais intensos nos animais que receberam detomidina. Os valores de PA apresentaram aumento inicial apenas no grupo detomidina, com duração de aproximadamente 30 minutos e posterior redução dos valores, sem caracterizar hipertensão ou hipotensão. Na avaliação ecodopplercardiográfica o GD apresentou maior depressão nos parâmetros de função ventricular, em relação ao GX. Com base nos valores obtidos em outros estudos utilizando métodos já consagrados, observou-se que a ecodopplercardiografia foi eficiente na avaliação hemodinâmica de equinos. Conclui-se que a detomidina promove sedação mais eficiente comparada à xilazina em equinos, no entanto os efeitos depressivos sobre as variáveis cardiovasculares são maiores, conforme avaliação ecodopplercardiográfica

L’asthme bronchique est caractérisé par un remodelage et une inflammation des voies aériennes. La masse du muscle lisse ainsi que la déposition de matrice extracellulaire sont augmentées dans la paroi des bronches asthmatiques, ce qui contribue à l’obstruction respiratoire. Peu d’études ont évalué les effets des traitements utilisés dans l’asthme sur le remodelage bronchique, et surtout peu de données sont disponibles concernant les effets sur le muscle lisse. La combinaison de corticostéroïdes et de β2-agonistes à longue durée d’action administrée par inhalation permet de mieux contrôler les crises d’asthme par rapport à la monothérapie avec des médicaments corticostéroïdes. Cependant, l’action spécifique de la combinaison sur le remodelage et sur l’inflammation des bronches périphériques n’est pas décrite. Surtout, il reste à clarifier si l’administration de la combinaison est avantageuse par rapport à la monothérapie corticostéroïde. La plupart des études réalisées chez l’homme utilisent des tissus bronchiques obtenus par biopsie endobronchique, qui ne sont pas représentatifs du processus pathologique affectant les voies respiratoires périphériques. Leur inaccessibilité par des méthodes non invasives est la raison pour laquelle si peu de données existent sur la pathophysiologie des voies périphériques chez les patients asthmatiques. L’asthme équin, aussi connu comme « le souffle », est une pathologie obstructive des chevaux adultes considérée comme un modèle animal d’asthme humain. Elle est caractérisée par un remodelage des bronches périphériques et par une inflammation bronchoalvéolaire de type neutrophilique. En étudiant le modèle équin, cette thèse a évalué la contribution des médicaments corticostéroïdes et de β2-agonistes à longue durée d’action, administrée comme monothérapies ou en combinaison, sur la réversibilité du remodelage et de l’inflammation de voies aériennes dans l’asthme bronchique. A cette fin, nous avons d’abord optimisé et validé l’application de la biopsie endobronchique et de l’échographie endobronchique chez le cheval adulte. Nos résultats indiquent que les échantillons obtenus par biopsie endobronchique sont inadéquats pour l’évaluation quantitative de la masse du muscle lisse chez le cheval. Cependant, ils permettent d’étudier les changements quantitatifs des structures épithéliales et de la lamina propria, ainsi que les aspects qualitatifs du muscle lisse. L’échographie endobronchique, quant à elle, permet d'estimer la masse du muscle lisse bronchique, et ce, chez des chevaux sains et chez des chevaux asthmatiques. Cette thèse démontre aussi que qu’un traitement de 12 semaines avec des corticostéroïdes induit une diminution significative de la masse du muscle lisse périphérique, qui n’est pas amélioré davantage par l’administration concomitante d’un β2-agoniste à longue durée d’action. Cette diminution est toutefois incomplète. Un effet positif et synergique de la combinaison a également été observé au niveau de la déposition de matrice extracellulaire. La combinaison a produit une diminution significative de la quantité de matrices déposées dans la lamina propria et dans la couche du muscle lisse dans les bronches centrales, alors que l’effet été limité à la couche du muscle lisse dans les bronches périphériques. La combinaison n’améliore pas le contrôle de l’inflammation bronchique ni bronchiolaire par rapport aux monothérapies ; cependant, elle diminue la neutrophilie bronchoalvéolaire de façon synergique. / Airway remodeling and inflammation are the hallmarks of asthma. Both airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition are increased in the central and peripheral airways of asthmatic patients, which contribute to airway obstruction. Few studies have investigated the ability of current asthma medications to reverse airway remodeling, especially the increased ASM mass. Inhaled corticosteroids (ICS) and long-acting β2-agonist combinations (ICS/LABA) are more effective than ICS monotherapy to control asthma exacerbations. However, their efficacy at modifying bronchial inflammation and remodeling at the peripheral level of the lung is not well-described. In fact, most work has been performed using endobronchial biopsy samples obtained from asthmatic subjects, which completely disregard the alterations occurring in peripheral airways. Ethical considerations limit the possibility of biopsying the peripheral airways in humans due to the invasiveness of the procedure. Equine asthma, or heaves, is a naturally-occurring disease of adult horses and a recognized animal model of human asthma characterized by neutrophilic inflammation as well as ASM and ECM remodeling of peripheral airways. This thesis has assessed the contribution of ICS and LABA, alone or combined, to the reversal of remodeling and inflammation in central and peripheral airways using the equine asthma model. To attain this goal, we have first optimized and validated the application of endobronchial biopsy and endobronchial ultrasound (EBUS) in the equine species. EBUS reliably estimates the bronchial ASM. Subsequently, asthmatic horses with ongoing airway remodeling and inflammation were treated with ICS, LABA, ICS/LABA, or antigen avoidance. Lung function, airway remodeling and inflammation were then assessed weekly for 3 months. Our results demonstrated a 30% decrease of peripheral ASM remodeling attained with ICS and ICS/LABA pharmacological treatment. A decrease of a similar magnitude of peripheral ASM was previously reported after 6 and 12 months of ICS monotherapy and antigen avoidance, respectively. A synergistic effect of ICS/LABA was observed on ECM deposition and airway lumen neutrophils. ICS/LABA decreased the ECM fraction of the ASM layer both peripherally and centrally, while the same effect on the lamina propria was observed only in central airways. Both ICS/LABA and ICS monotherapy decreased submucosal inflammation in central airways, while only ICS/LABA and antigen avoidance decreased bronchoalveolar neutrophilia. In conclusion, our results suggest that the enhanced therapeutic effect of ICS/LABA over ICS monotherapy in asthmatic horses was associated with a reduction of ECM deposition, mainly observed within the large airways, and possibly also with a decreased airway neutrophilia. However, ICS/LABA did not provide additional benefit to ICS monotherapy in terms of peripheral ASM remodeling as both induce a 30% decrease of the ASM mass in 3 months.