Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 43-54). Also available via the Internet.

Os agonistas alfa 2 adrenérgicos são sedativos empregados na rotina clínica de ruminantes, e têm, entre outras, a vantagem de possuir antagonistas específicos, que aumentam a segurança no uso destes medicamentos. Tendo em vista a escassez de estudos acerca dos parâmetros hemodinâmicos e respiratórios em ovinos em posição quadrupedal e submetidos à sedação com xilazina ou dexmedetomidina com posterior reversão pelo atipamezole, realizou-se o presente estudo. Para tanto, foram utilizados 12 ovinos, machos, com idade entre um e dois anos, peso médio de 37,7kg, distribuídos em dois grupos de seis animais que foram submetidos a dois tratamentos distintos com média de três semanas de intervalo, em estudo do tipo prospectivo, encoberto e aleatório, sendo designados como Grupo XILA (cloridrato de xilazina 0,2 mg/kg IM) e Grupo DEX (cloridrato de dexmedetomidina 15 µg/kg IM). Para a instalação do cateter de artéria pulmonar os animais foram anestesiados com auxílio de máscara facial com isofluorano em oxigênio, e na sequência foram intubados e mantidos sob anestesia com o mesmo agente até o fim da instrumentação. Após a recuperação anestésica foram avaliados os parâmetros hemodinâmicos, hemogasométricos e respiratórios durante os primeiros 60 minutos com os animais em posição quadrupedal, para obtenção dos parâmetros basais. Finalizada esta avaliação, os animais foram submetidos aos protocolos de sedação segundo o seu grupo. Os parâmetros foram verificados e registrados aos cinco (S5), 15 (S15) e 30 minutos (S30) após sedação, e, após a aplicação de 30 µg/kg IM de atipamezole aos cinco (R5) e 15 minutos (R15). Foram avaliados frequência e ritmo cardíaco, pressão arterial sistêmica, parâmetros hemodinâmicos, frequência respiratória, hemogasometria arterial e venosa mista, temperatura central, glicemia e grau de sedação. Os índices ventilatórios e hemodinâmicos foram calculados. O período de latência em XILA e DEX foram 3,9 e 5,2 minutos. A xilazina promoveu sedação mais intensa, com diferença significativa entre os grupos aos 5 e 15min após sedação (momentos S5 e S15). Após a sedação, observou-se redução significativa da frequência cardíaca nos dois grupos, que refletiu no débito cardíaco, índice cardíaco e pressão arterial média. Houve elevação não significativa da resistência vascular sistêmica em ambos os grupos, mas que após o atipamezole ficou significativamente mais baixa no grupo XILA. A xilazina causou taquipneia, que foi inibida após o atipamezole. Não houve alterações clinicamente importantes nos valores de PaCO2, PaO2, SaO2 e nem nos índices de ventilação, indicando que não ocorreu hipoxemia, hipercapnia ou hipoventilação durante a sedação. A glicemia elevou-se de maneira significativa nos dois grupos mantendo-se elevada mesmo após o antagonista. Após administração do atipamezole os animais levaram 10,0 e 11,7 minutos para ficarem em posição quadrupedal e 19,3 e 30 minutos para reversão dos efeitos da xilazina e da dexmedetomidina, respectivamente. Tanto a xilazina como a dexmedetomidina promoveram sedação segura, com poucos efeitos hemodinâmicos e cardiorrespiratórios, sugerindo que a administração pela via intramuscular seja adequada para sedação de ovinos com xilazina ou dexmedetomidina / Adrenergic alpha 2 agonists are sedatives used in ruminants clinical routine and have, among others, the advantage of specific antagonists which increase the safety of these drugs. Given the scarcity of studies on the hemodynamic and respiratory parameters in sheep in standing position and undergoing sedation with xylazine or dexmedetomidine with subsequent reversal by atipamezol, this study was performed. For this purpose were used 12 male sheep, aged between one and two years, average weight 37,7kg. Sheep were divided into two groups of six animals that were submitted to two different treatments with a mean interval of three weeks, in a study of prospective hidden and random type, being designated as XILA Group (xylazine hydrochloride 0.2 mg/kg) and DEX Group (dexmedetomidine hydrochloride 15 µg/kg) given by intramuscular route. For the installation of pulmonary artery catheter, the animals were anesthetized with facial mask with isofluorane in oxygen, and were intubated and maintained under anesthesia with the same agent until the end of instrumentation. After recovery of anesthesia, we evaluated the hemodynamic, blood gas and respiratory parameters during the first 60 minutes with animals in standing position, to obtain the baseline parameters. Completed this evaluation, the animals were submitted to sedation protocols according to their group. The parameters were checked and registered to 5 (S5), 15 (S15) and 30 minutes (S30) after sedation, and after application of 30 µg/kg atipamezole by intramuscular route to 5 (R5) and 15 minutes (R15). Frequency and heart rate, systemic blood pressure, hemodynamic parameters, respiratory rate, arterial and mixed venous blood gas analysis, core temperature, blood glucose and degree of sedation were evaluated. Ventilatory and hemodynamic indices were calculated. The onset period in XILA and DEX were 3.9 and 5.2 minutes. Xylazine promoted more intense sedation, with a significant difference between the groups at 5 and 15 minutes after alpha 2 administration (S5 and S15). After sedation, significant decrease in heart rate was observed in both groups, which reflected in cardiac output, cardiac index and mean arterial pressure. There was no significant increase in systemic vascular resistance in both groups, but after atipamezol was significantly lower in the XILA group. Xylazine caused tachypnea, which was inhibited after atipamezol. There were no clinically significant changes in PaCO2, PaO2, SaO2 nor in the ventilation indices, indicating that there was no hypoxemia, hypercapnia or hypoventilation during sedation period. Blood glucose rose significantly in both groups, remained higher even after antagonist. After administration of atipamezol sheep needed 10.0 and 11.7 minutes to remain in standing position and 19.3 and 30 minutes to reverse the effects of dexmedetomidine and xylazine, respectively. Xylazine and dexmedetomidine promoted safe sedation with few hemodynamic and cardiorespiratory effects, suggesting that the intramuscularly route is suitable for sedation of sheep with xylazine or dexmedetomidine

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-18Bitstream added on 2014-06-13T19:20:15Z : No. of bitstreams: 1 silvajunior_jr_dr_jabo.pdf: 913369 bytes, checksum: 3bdbada76534ca341602e017a918fbd1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os efeitos antinociceptivos, comportamentais (atividade locomotora espontânea - ALE, altura de cabeça - AC) e sobre as variáveis fisiológicas de seis equinos tratados com tramadol, como agente analgésico preventivo, nas doses intravenosas de 2 (TT2), 3 (TT3) e 5 mg/kg (TT5), assim como da associação tramadol (3 mg/kg) e xilazina (0,5 mg/kg) (TTX) ou ainda da xilazina (0,5 mg/kg) isolada (TX) foram avaliados. Para ALE, diferenças (P<0,05) foram observadas entre os grupos TT2, TT3 e TT5, porém estas não foram significativas (P>0,05) entre esses e os grupos TTX e TX. Para a AC os grupos TTX e TX foram semelhantes sendo esses diferentes dos grupos tratados com tramadol isolado (P<0,05). Diferenças não foram observadas (P>0,05) quanto à ação antinociceptiva. No grupo TTX as variações nas frequências cardíaca e respiratória, pressão arterial sistólica e motilidade intestinal foram significativas (P<0,05). Pode-se concluir pelo exposto que, embora o tramadol isoladamente não promova alteração significativa no estado comportamental de equinos, não constitui um fármaco analgésico somático ao menos para o estímulo usado, e que a associação tramadol/xilazina, não constitui uma opção como associação, visando à sedação e à analgesia, principalmente quando for desejado incrementar, nas técnicas de anestesia, a antinocicepção somática preventiva. / Antinociceptive and behavioral effects (spontaneous locomotor activity [SLA] and head height [HH]) and effects on physiological parameters in six horses treated with tramadol as a preventive analgesic agent were assessed. Tramadol was administered at intravenous doses of 2 (TT2), 3 (TT3) and 5 mg/kg (TT5), as well as a combination of tramadol (3 mg/kg) and xylazine (0.5 mg/kg) (TTX) or xylazine alone (0.5 mg/kg) (TX). Differences in SLA (P<0.05) were seen in TT2, TT3, and TT5 groups but they were not statistically significant (P>0.05) between these groups and TTX and TX groups. TTX and TX groups showed similar HHs but there were differences of HH between TTX and TX and those groups treated with tramadol alone (P<0.05). However, no differences (P>0.05) were found regarding antinociceptive action. Significant changes (P<0.05) of heart and respiratory rates, systolic blood pressure, and intestinal motility were seen in TTX group. Although tramadol alone does not have a significant effect on horse behavior, it failed to produce analgesia and it has no somatic analgesic action to the stimulus studied. In conclusion, the combination of tramadol plus xylazine should be carefully prescribed to patients with prior cardiovascular and gastrointestinal conditions but it is not an adequate drug combination for sedation and analgesia, especially when anesthesia is intended to increase preventive somatic antinociception.

Made available in DSpace on 2014-06-11T19:23:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-07-27Bitstream added on 2014-06-13T20:30:35Z : No. of bitstreams: 1 escobar_a_me_jabo.pdf: 469077 bytes, checksum: 4db0fafd9bab3f1993358cf18a557b9d (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Foram avaliados os efeitos cardiovasculares e comportamentais após a administração intravenosa de amitraz ou xilazina em oito gatos. Todos os animais foram submetidos aos três tratamentos, a saber: GXil - 1 mg/kg de xilazina; GAmz - 1 mg/kg de amitraz em diluente lipídico; e GDil - volume de diluente lipídico idêntico ao utilizado nos animais tratados com amitraz, respeitando-se um intervalo mínimo de 15 dias entre eles. Imediatamente antes dos tratamentos, avaliaram-se à pressão arterial sistólica (PAS), temperatura retal (T), freqüência respiratória (f), ritmo, freqüência (FC), índice (IC) e contratilidade cardíaca. Os demais registros foram realizados aos 5, 10, 15, 20, 30, 40, 50 e 60 minutos após os tratamentos. Empregou-se análise de variância (ANOVA) de uma única via e teste de Friedman, ambos seguidos pelo teste de Tukey (p=0,05), respectivamente para os dados paramétricos e não-paramétricos. Tanto o amitraz como a xilazina causaram bloqueios atrioventriculares de 1º grau e redução da FC, frações de ejeção (FE) e de encurtamento (FS), IC, PAS e T. Complexos ventriculares prematuros foram observados após a aplicação de amitraz ou do diluente, e a f aumentou. O amitraz induziu sedação menos intensa do que a xilazina. Conclui-se que ambos induzem bradicardia e BAV de 1º grau, observando-se maior depressão da contratilidade cardíaca para a xilazina. A dose empregada do amitraz produz efeito sedativo em gatos. / To evaluate the cardiovascular and behavioral alterations, eight cats were submitted to amitraz or xylazine intravenous injection: GXil - 1 mg/kg of xylazine; GAmz - 1 mg/kg of amitraz; and GDil - diluent in equal volume used on GAmz. The same cats were used after a 15 day interval. Systolic arterial blood pressure (SAP), temperature (T), respiratory (RR) and heart rates (HR), cardiac index (CI), rhythm and contractility (ejection fraction - EF and shortening fraction - SF) were measured before treatments and 5, 10, 15, 20, 30, 40, 50 and 60 minutes after each treatment. One way analysis of variance (ANOVA) and Friedman test, followed by Tukey test (p=0.05), were used to compare parametric and non-parametric data, respectively. Amitraz and xylazine induced first-degree A-V block, decreased HR, EF, SF, CI, SAP and T. Ventricular premature complexes were noted after amitraz or diluent injection, and RR increased. Amitraz induced a lower sedative effect compared to xylazine. It was concluded that both a2-agonists produce bradycardia and first-degree A-V block, but xylazine causes greater cardiac contractility depression. Additionally, amitraz produces a sedative effect in cats.

Os agonistas alfa 2 adrenérgicos são sedativos empregados na rotina clínica de ruminantes, e têm, entre outras, a vantagem de possuir antagonistas específicos, que aumentam a segurança no uso destes medicamentos. Tendo em vista a escassez de estudos acerca dos parâmetros hemodinâmicos e respiratórios em ovinos em posição quadrupedal e submetidos à sedação com xilazina ou dexmedetomidina com posterior reversão pelo atipamezole, realizou-se o presente estudo. Para tanto, foram utilizados 12 ovinos, machos, com idade entre um e dois anos, peso médio de 37,7kg, distribuídos em dois grupos de seis animais que foram submetidos a dois tratamentos distintos com média de três semanas de intervalo, em estudo do tipo prospectivo, encoberto e aleatório, sendo designados como Grupo XILA (cloridrato de xilazina 0,2 mg/kg IM) e Grupo DEX (cloridrato de dexmedetomidina 15 &micro;g/kg IM). Para a instalação do cateter de artéria pulmonar os animais foram anestesiados com auxílio de máscara facial com isofluorano em oxigênio, e na sequência foram intubados e mantidos sob anestesia com o mesmo agente até o fim da instrumentação. Após a recuperação anestésica foram avaliados os parâmetros hemodinâmicos, hemogasométricos e respiratórios durante os primeiros 60 minutos com os animais em posição quadrupedal, para obtenção dos parâmetros basais. Finalizada esta avaliação, os animais foram submetidos aos protocolos de sedação segundo o seu grupo. Os parâmetros foram verificados e registrados aos cinco (S5), 15 (S15) e 30 minutos (S30) após sedação, e, após a aplicação de 30 &micro;g/kg IM de atipamezole aos cinco (R5) e 15 minutos (R15). Foram avaliados frequência e ritmo cardíaco, pressão arterial sistêmica, parâmetros hemodinâmicos, frequência respiratória, hemogasometria arterial e venosa mista, temperatura central, glicemia e grau de sedação. Os índices ventilatórios e hemodinâmicos foram calculados. O período de latência em XILA e DEX foram 3,9 e 5,2 minutos. A xilazina promoveu sedação mais intensa, com diferença significativa entre os grupos aos 5 e 15min após sedação (momentos S5 e S15). Após a sedação, observou-se redução significativa da frequência cardíaca nos dois grupos, que refletiu no débito cardíaco, índice cardíaco e pressão arterial média. Houve elevação não significativa da resistência vascular sistêmica em ambos os grupos, mas que após o atipamezole ficou significativamente mais baixa no grupo XILA. A xilazina causou taquipneia, que foi inibida após o atipamezole. Não houve alterações clinicamente importantes nos valores de PaCO2, PaO2, SaO2 e nem nos índices de ventilação, indicando que não ocorreu hipoxemia, hipercapnia ou hipoventilação durante a sedação. A glicemia elevou-se de maneira significativa nos dois grupos mantendo-se elevada mesmo após o antagonista. Após administração do atipamezole os animais levaram 10,0 e 11,7 minutos para ficarem em posição quadrupedal e 19,3 e 30 minutos para reversão dos efeitos da xilazina e da dexmedetomidina, respectivamente. Tanto a xilazina como a dexmedetomidina promoveram sedação segura, com poucos efeitos hemodinâmicos e cardiorrespiratórios, sugerindo que a administração pela via intramuscular seja adequada para sedação de ovinos com xilazina ou dexmedetomidina / Adrenergic alpha 2 agonists are sedatives used in ruminants clinical routine and have, among others, the advantage of specific antagonists which increase the safety of these drugs. Given the scarcity of studies on the hemodynamic and respiratory parameters in sheep in standing position and undergoing sedation with xylazine or dexmedetomidine with subsequent reversal by atipamezol, this study was performed. For this purpose were used 12 male sheep, aged between one and two years, average weight 37,7kg. Sheep were divided into two groups of six animals that were submitted to two different treatments with a mean interval of three weeks, in a study of prospective hidden and random type, being designated as XILA Group (xylazine hydrochloride 0.2 mg/kg) and DEX Group (dexmedetomidine hydrochloride 15 &micro;g/kg) given by intramuscular route. For the installation of pulmonary artery catheter, the animals were anesthetized with facial mask with isofluorane in oxygen, and were intubated and maintained under anesthesia with the same agent until the end of instrumentation. After recovery of anesthesia, we evaluated the hemodynamic, blood gas and respiratory parameters during the first 60 minutes with animals in standing position, to obtain the baseline parameters. Completed this evaluation, the animals were submitted to sedation protocols according to their group. The parameters were checked and registered to 5 (S5), 15 (S15) and 30 minutes (S30) after sedation, and after application of 30 &micro;g/kg atipamezole by intramuscular route to 5 (R5) and 15 minutes (R15). Frequency and heart rate, systemic blood pressure, hemodynamic parameters, respiratory rate, arterial and mixed venous blood gas analysis, core temperature, blood glucose and degree of sedation were evaluated. Ventilatory and hemodynamic indices were calculated. The onset period in XILA and DEX were 3.9 and 5.2 minutes. Xylazine promoted more intense sedation, with a significant difference between the groups at 5 and 15 minutes after alpha 2 administration (S5 and S15). After sedation, significant decrease in heart rate was observed in both groups, which reflected in cardiac output, cardiac index and mean arterial pressure. There was no significant increase in systemic vascular resistance in both groups, but after atipamezol was significantly lower in the XILA group. Xylazine caused tachypnea, which was inhibited after atipamezol. There were no clinically significant changes in PaCO2, PaO2, SaO2 nor in the ventilation indices, indicating that there was no hypoxemia, hypercapnia or hypoventilation during sedation period. Blood glucose rose significantly in both groups, remained higher even after antagonist. After administration of atipamezol sheep needed 10.0 and 11.7 minutes to remain in standing position and 19.3 and 30 minutes to reverse the effects of dexmedetomidine and xylazine, respectively. Xylazine and dexmedetomidine promoted safe sedation with few hemodynamic and cardiorespiratory effects, suggesting that the intramuscularly route is suitable for sedation of sheep with xylazine or dexmedetomidine

The aim of this study was to determine the contractile responses of normal virgin rat uterine smooth muscle to the ⍺₂ adrenergic agonist, xylazine HCl, in the presence or absence of the selective ⍺₂ adrenoceptor blocker, idazoxan HCl. Sections of full thickness uterus measuring 5 x 1 x 1 mm taken from mature, virgin Sprague-Dawley rats were used in isolated tissue baths containing 37°C Krebs-bicarbonate solution, and continually aerated with 95% O₂ and 5% CO₂. Following stabilization of spontaneous contractions, the tissues were exposed to either no idazoxan (control), 10⁻⁵ M idazoxan (low), 10⁻⁴ M idazoxan (medium), or 10⁻³ M idazoxan (high). Five minutes later, xylazine was added to all baths in a cumulative manner at quarter log increments from 1 x 10⁻⁵ through 1 x 10⁻³ M. The % response in peak developed tension and effective concentration resulting in a 50% response (EC₅₀) for the four treatment groups were examined. Results indicated that xylazine alone, at a concentrations greater than 1 x 10⁻⁴ M, caused a significant negative inotropic response. Pre-treatment with idazoxan at a concentration greater than 10⁻⁴ M enhanced the negative inotropic effect of xylazine in a dose-dependent manner. The mechanism of this synergism is unknown but is proposed to be a local anesthetic action due to sodium channel blockade. / Master of Science

Présentement, le diagnostic d’otite moyenne-interne chez le veau est basé sur la présence de signes cliniques appropriés ainsi que les tests diagnostiques tels que la radiographie et la tomodensitométrie. L’objectif de cette étude prospective était d’évaluer les valeurs prédictives de l’examen neurologique, l’examen otoscopique et le test des potentiels auditifs évoqués (PAE) dans le diagnostic d’otite moyenne-interne chez le veau, en utilisant la tomodensitométrie comme test standard. Le deuxième objectif était de définir les valeurs de référence pour le PAE chez le veau normal et d’en décrire les anomalies chez des veaux atteints d’otite moyenne-interne. Dix-sept veaux de race Holstein entre 5-7 semaines d’âge ont été inclus. Tous les veaux ont eu un examen neurologique, un examen otoscopique et une évaluation des PAEs. Les veaux ont été tranquillisés avec de la xylazine intraveineuse (0,05-0,15mg/kg) pour la tomodensitométrie des bulles tympaniques afin d’évaluer pour la présence d’otite moyenne-interne. Selon les résultats de la tomodensitométrie, 11 des 17 veaux étaient atteints avec otite moyenne, 4 de façon unilatérale et 7 bilatéralement. Cinq ondes ont été identifiées de façon constante sur les tracés des PAEs des 6 veaux normaux. Les valeurs positives prédictives pour le PAE, l’examen neurologique et l’examen otoscopique étaient 94,7%, 91,7% et 66,7% respectivement. D’un point de vue clinique, le test le plus fiable dans le diagnostic d’otite moyenne-interne chez le veau est le PAE. Les anomalies ont été observées au PAE avant le développement des signes neurologiques chez certains veaux. / Currently, the antemortem diagnosis of otitis media-interna is based upon the presence of appropriate clinical signs and adjunctive diagnostic imaging including radiography and computed tomography. The purpose of this prospective study was to evaluate predictive values of neurological examination, otoscopic examination and BAER in calves for the diagnosis of otitis media-interna using computed tomography as the gold standard. The second objective was to define BAER reference values in normal calves and to describe BAER abnormalities in calves affected with otitis media-interna. Seventeen Holstein calves between 5 and 7 weeks of age were included. All calves had a neurological examination, otoscopic examination and BAER. Calves were sedated with intravenous xylazine (0.05-0.15 mg/kg [0.02-0.07 mg/lb]) for computed tomography of the tympanic bullae to evaluate for the presence of otitis media-interna. Based upon computed tomographic results, 11 of 17 calves were affected with otitis media, 4 unilaterally and 7 bilaterally. Five waveforms were consistently identified on BAER traces from 6 normal calves. The positive predictive value of BAER, neurological examination and otoscopic examination were 94.7%, 91.7% and 66.7% respectively. Clinically, the most reliable non-invasive diagnostic test to diagnose otitis media-interna in the calf is the BAER. Abnormalities were observed on BAER before the development of neurological deficits in approximately 40% of calves allowing earlier diagnosis.

Lorsque l’anesthésie par inhalation ne peut être utilisée chez le rat, la combinaison de kétamine et de xylazine est l’alternative la plus fréquemment utilisée. Les doses administrées peuvent varier selon le protocole expérimental. En présence de fièvre, d’infections ou de processus tumoral accompagné de fièvre, la pharmacocinétique de ces drogues peut être modifiée. Ce projet porte sur l’évaluation des changements physiologiques, hématologiques, biochimiques et pharmacocinétiques chez le rat Sprague Dawley lors d’anesthésie avec le mélange kétamine-xylazine suite à l’administration de trois doses différentes de lipopolysaccharide (LPS). Après l’administration de LPS, une anesthésie à la kétamine-xylazine fut induite chez des rats Sprague Dawley. Des prélèvements sanguins périodiques ainsi que des mesures des paramètres physiologiques furent effectués afin d’évaluer l’effet du LPS sur la pharmacocinétique des deux drogues ainsi que sur les paramètres biochimiques et hématologiques. Les différentes doses de LPS ont causé certaines modifications notamment en produisant une baisse marquée de la saturation en oxygène et de l’albumine sérique, une augmentation de la durée d’anesthésie ainsi que des lésions hépatiques mineures. Les paramètres pharmacocinétiques de la kétamine furent peu altérés par l’administration de LPS tandis qu’une diminution de la clairance et une augmentation de l’aire sous la courbe (AUC) furent observées pour la xylazine dans les groupes ayant reçu les doses moyenne et élevée de LPS. Ces résultats montrent que les doses de xylazine doivent être adaptées en présence de LPS pour permettre une anesthésie de courte durée et des changements physiologiques et biochimiques moindres lorsqu’elle est administrée avec de la kétamine. / When inhalation anesthesia cannot be used in laboratory rats, ketamine-xylazine combination is the most frequent alternate regimen. The administrated doses can vary according to the experimental protocol. During fever episodes, infections or tumoral process, the pharmacokinetics of these drugs can be modified. This project focuses on the evaluation of the physiological, hematological, biochemical and pharmacokinetics changes in Sprague Dawley rats during ketamine-xylazine anesthesia, after administration of three different doses of lipopolysaccharide (LPS). After administration of LPS to Sprague Dawley rats, ketamine-xylazine anesthesia was induced. Periodic blood samplings and monitoring of physiologic parameters were made in order to evaluate the effect of LPS on ketamine-xylazine pharmacokinetics and hematological and biochemical parameters. The different LPS doses caused specific parameter modifications including a marked decrease of oxygen blood saturation and serum albumin, a longer anesthesia duration and minor hepatic lesions. No significant modifications of pharmacokinetics parameters of ketamine were observed. An increase of area under curve (AUC) and a decrease of xylazine clearance were noted in groups who received medium and large doses of LPS. These results show that that xylazine doses need to be adapted in the presence of LPS, to allow a shorter duration anaesthesia and lesser physiological and biochemical changes when administered with ketamine.

Chez les animaux de laboratoire, même si les anesthésiques par inhalation sont généralement plus sécuritaires que les injectables, leur utilité est souvent restreinte lorsqu’un protocole expérimental exige une autre approche. Des combinaisons d’anesthésiques contenant de la kétamine sont considérées comme l’option de choix pour les anesthésies injectables chez les rats. Le vieillissement entraîne des changements dégénératifs au niveau de la structure et la fonction des organes, modifiant souvent à la pharmacocinétique des drogues. Ce projet porte sur l’évaluation des changements pharmacodynamiques (physiologiques, biochimiques et histologiques) et pharmacocinétiques, lors d’une combinaison anesthésique de kétamine-­‐xylazine chez le rat Sprague-­‐Dawley vieillissant. Une anesthésie à la kétamine-­‐xylazine fut induite chez des rats Sprague-­‐Dawley de différents âges. Afin d’évaluer l’effet du vieillissement sur le métabolisme des deux drogues, des prélèvements sanguins périodiques pour l’analyse de la pharmacocinétique ainsi que des mesures des paramètres physiologiques, biochimiques et une histopathologie furent effectués. Le vieillissement a causé certaines modifications notamment en produisant une diminution de la saturation d’oxygène, une baisse marquée de la fréquence cardiaque et respiratoire, une hypoalbuminémie ainsi qu’une augmentation de la durée d’anesthésie. Les paramètres pharmacocinétiques de la kétamine et de la xylazine furent grandement affectés par le vieillissement causant une augmentation progressive significative de l’aire sous la courbe (AUC) et du temps de demi-­‐vie, ainsi qu’une diminution de la clairance. À la lumière de ces résultats, les doses de kétamine et de xylazine doivent être adaptées chez les rats vieillissants pour permettre une anesthésie de durée raisonnable et un réveil sans complications. / In laboratory animals, even if inhalation anesthetics are generally safer than injecting, their usefulness is often restrained when an experimental design does not allow it. For this reason, ketamine combinations are considered the option of choice for injecting anesthesia in rats. Aging brings degenerative changes in the structure and function of the organs, often affecting the pharmacokinetics of drugs. This project focuses on the evaluation of physiological, pharmacokinetic, biochemical and histological changes during a ketamine-­‐xylazine anesthetic combination in aging Sprague-­‐Dawley rats. Anesthesia with ketamine-­‐xylazine was induced in Sprague-­‐Dawley rats of different ages. To assess the effect of aging on the metabolism of both drugs, periodic blood samples for pharmacokinetic analysis and measurements of physiological, biochemical and histological parameters were performed. Aging have made some changes for example a decrease in oxygen saturation, a sharp drop in heart and respiratory rate, hypoalbuminemia and an increase in the duration of anesthesia. The pharmacokinetic parameters of ketamine and xylazine were greatly affected in older animals, causing a significant increase in the area Under the curve (AUC) and the half-­‐life time, and a decrease in clearance. In the light of these results, dosage of ketamine and xylazine must be adapted in aging rats to allow a short anesthesia and an awakening without complications.

Lorsque l’anesthésie par inhalation ne peut être utilisée chez le rat, la combinaison de kétamine et de xylazine est l’alternative la plus fréquemment utilisée. Les doses administrées peuvent varier selon le protocole expérimental. En présence de fièvre, d’infections ou de processus tumoral accompagné de fièvre, la pharmacocinétique de ces drogues peut être modifiée. Ce projet porte sur l’évaluation des changements physiologiques, hématologiques, biochimiques et pharmacocinétiques chez le rat Sprague Dawley lors d’anesthésie avec le mélange kétamine-xylazine suite à l’administration de trois doses différentes de lipopolysaccharide (LPS). Après l’administration de LPS, une anesthésie à la kétamine-xylazine fut induite chez des rats Sprague Dawley. Des prélèvements sanguins périodiques ainsi que des mesures des paramètres physiologiques furent effectués afin d’évaluer l’effet du LPS sur la pharmacocinétique des deux drogues ainsi que sur les paramètres biochimiques et hématologiques. Les différentes doses de LPS ont causé certaines modifications notamment en produisant une baisse marquée de la saturation en oxygène et de l’albumine sérique, une augmentation de la durée d’anesthésie ainsi que des lésions hépatiques mineures. Les paramètres pharmacocinétiques de la kétamine furent peu altérés par l’administration de LPS tandis qu’une diminution de la clairance et une augmentation de l’aire sous la courbe (AUC) furent observées pour la xylazine dans les groupes ayant reçu les doses moyenne et élevée de LPS. Ces résultats montrent que les doses de xylazine doivent être adaptées en présence de LPS pour permettre une anesthésie de courte durée et des changements physiologiques et biochimiques moindres lorsqu’elle est administrée avec de la kétamine. / When inhalation anesthesia cannot be used in laboratory rats, ketamine-xylazine combination is the most frequent alternate regimen. The administrated doses can vary according to the experimental protocol. During fever episodes, infections or tumoral process, the pharmacokinetics of these drugs can be modified. This project focuses on the evaluation of the physiological, hematological, biochemical and pharmacokinetics changes in Sprague Dawley rats during ketamine-xylazine anesthesia, after administration of three different doses of lipopolysaccharide (LPS). After administration of LPS to Sprague Dawley rats, ketamine-xylazine anesthesia was induced. Periodic blood samplings and monitoring of physiologic parameters were made in order to evaluate the effect of LPS on ketamine-xylazine pharmacokinetics and hematological and biochemical parameters. The different LPS doses caused specific parameter modifications including a marked decrease of oxygen blood saturation and serum albumin, a longer anesthesia duration and minor hepatic lesions. No significant modifications of pharmacokinetics parameters of ketamine were observed. An increase of area under curve (AUC) and a decrease of xylazine clearance were noted in groups who received medium and large doses of LPS. These results show that that xylazine doses need to be adapted in the presence of LPS, to allow a shorter duration anaesthesia and lesser physiological and biochemical changes when administered with ketamine.