Relative potency of ketamine and S(+)-ketamine in dogs

The aim of this study was to determine the relative potency of racemic ketamine and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)-ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter with S(+)-ketamine. It was concluded that the potency ratio between ketamine and S(+)-ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.

Efeitos do desfluorano, sevofluorano e isofluorano sobre variáveis respiratórias e hemogasométricas em cães

Com este estudo objetivou-se avaliar, comparativamente, os efeitos de três anestésicos inalatórios sobre variáveis respiratórias e hemogasométricas em cães. Para tal, utilizaram-se 30 cães sadios, adultos, machos e fêmeas evitando-se aquelas em estro ou em gestação. Os animais foram separados e protocolados em três grupos de 10 cães cada (G1, G2 e G3). Induziu-se a anestesia geral com administração intravenosa de propofol, na dose de 10±1,3 mg/kg. em seguida procedeu-se à intubação orotraqueal e anestesia geral inalatória pelo desfluorano (G1), sevofluorano (G2) e isofluorano (G3), diluídos em oxigênio a 100,00%, por meio de circuito anestésico tipo semi-fechado, dotado de vaporizadores calibrados para cada agente anestésico. As variáveis estudadas foram Freqüência Respiratória, CO2 ao Final da Expiração, Saturação de Oxihemoglobina, Volume Corrente, Volume Minuto, Pressão Parcial Arterial de O2, Pressão Parcial Arterial de CO2, Excesso de Bases e pH. A avaliação estatística destas variáveis foi realizada pela Análise de Perfil, sendo considerado o nível de significância de 5,00%. Os resultados obtidos permitiram concluir que o desfluorano deprime o sistema respiratório aumentando a pressão parcial arterial de CO2 e o CO2 ao final da expiração; e diminuindo a pressão parcial arterial de O2 e o volume minuto, quando comparado com os outros anestésicos em teste.

Variabilidade da freqüência cardíaca em cães anestesiados com infusão contínua de propofol e sufentanil

Foram avaliados os efeitos do propofol associado ao sufentanil sobre o balanço das atividades simpática e parassimpática do coração, investigando-se um possível efeito dose dependente do opióide. Analisou-se a variabilidade da freqüência cardíaca (VFC) de 12 cães adultos pré-medicados com maleato de acepromazina e anestesiados com propofol e três doses diferentes de sufentanil, que variou de 0,025 a 0,1µg/kg/min. Registrou-se o eletrocardiograma 15 minutos após a medicação pré-anestésica e 15, 30, 60, 90 e 120 minutos após a indução anestésica. A VFC foi calculada no domínio da freqüência, mediante análise de 10 intervalos RR consecutivos. Houve redução acentuada da freqüência cardíaca, mas a VFC permaneceu relativamente inalterada.

In vitro and in vivo evaluation of a primaquine prodrug without red blood cell membrane destabilization property

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tigecycline: A Review of Properties, Applications, and Analytical Methods

Tigecycline is a new glycylcycline with an expanded broad-spectrum antibiotic, including inhibition of Gram-positive, Gram-negative, atypical, anaerobic, and antibiotic-resistant organisms. Trials have demonstrated that tigecycline is noninferior to the comparators for the treatment of complicated skin and skin structure infections as well as complicated intra-abdominal infections. Tigecycline is only available as an intravenous preparation and analytical methods to its quantitation in pharmaceutical products has not been published to date. This review examined tigecycline characteristics, the spectrum and mechanism of action, pharmacokinetics, applications, and, mainly, the instrumental conditions of published chromatographic methods used to measure tigecycline, its metabolites, and some analogs in clinical and biologic research.

Social defeat stress in rats: escalation of cocaine and speedball binge self-administration, but not heroin

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination (speedball).Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin-cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking.A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The semi-synthetic kaurane ent-16 alpha-methoxykauran-19-oic acid induces vascular relaxation and hypotension in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bed nucleus of the stria terminalis and the cardiovascular responses to chemoreflex activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of laryngeal mask as an alternative to endotracheal intubation in cats anesthetized under spontaneous or controlled ventilation

Objective To compare the cardiorespiratory effects and incidence of gastroesophageal reflux with the use of a laryngeal mask airway (LMA) or endotracheal tube (ET) in anesthetized cats during spontaneous (SV) or controlled ventilation (CV).Study design Prospective randomized experimental trial.Animals Thirty-two adult crossbred cats, weighing 2.7 +/- 0.4 kg.Methods the cats were sedated with intramuscular (IM) methotrimeprazine (0.5 mg kg(-1)) and buprenorphine (0.005 mg kg(-1)), followed 30 minutes later by induction of anesthesia with intravenous (IV) thiopental (12.5-20 mg kg(-1)). An ET was used in 16 cats and an LMA in the remaining 16 animals. Anesthesia was maintained with 0.5 minimum alveolar concentration (0.6%) of halothane in oxygen using a Mapleson D breathing system. Cats in both groups were further divided into two equal groups (n = 8), undergoing either SV or CV. Neuromuscular blockade with pancuronium (0.06 mg kg(-1)) was used to facilitate CV. Heart and respiratory rates, direct arterial blood pressure, capnometry (PE'CO2) and arterial blood gases were measured. Gastric reflux and possible aspiration was investigated by intragastric administration of 5 mL of radiographic contrast immediately after induction of anesthesia. Cervical and thoracic radiographs were taken at the end of anesthesia. Data were analyzed using ANOVA followed by Student-Newman-Keuls, Kruskal-Wallis or Friedman test where appropriate.Results Values for PaCO2 and PE'CO2 were higher in spontaneously breathing cats with the LMA when compared with other groups. Values of PaO2 and hemoglobin oxygen saturation did not differ between groups. Gastroesophageal reflux occurred in four of eight and two of eight cats undergoing CV with ET or LMA, respectively. There was no tracheal or pulmonary aspiration in any cases.Conclusions and clinical relevance the use of an LMA may be used as an alternative to endotracheal intubation in anesthetized cats. Although aspiration was not observed, gastric reflux may occur in mechanically ventilated animals.

Glibenclamide effects on renal function and histology after acute hemorrhage in rats under sevoflurane anesthesia

Introduction. Hypovolemia from hemorrhage evokes protective compensatory reactions, such as the renin-angiotensin system, which interferes in the clearance function and can lead to ischemia. This study was designed to evaluate the effects of glibenclamide, a K-ATP(+) channel blocker, on renal function and histology in rats in a state of hemorrhagic shock under sevoflurane anesthesia. Material and Methods. Twenty Wistar rats were randomized into two groups of 10 animals each (G1 and G2), only one of which (G2) received intravenous glibenclamide (1 mu g.g(-1)), 60 min before bleeding was begun. Both groups were anesthetized with sevoflurane and kept on spontaneous respiration with oxygen-air, while being bled of 30% of volemia in three stages with 10 min intervals. There was an evaluation of renal function-sodium para-aminohippurate and iothalamate clearances, filtration fraction, renal blood flow, renal vascular resistance-and renal histology. Renal function attributes were evaluated at three moments: M1 and M2, coinciding with the first and third stages of bleeding; and M3, 30 min after M2, when the animals were subjected to bilateral nephrectomy before being sacrificed. Results. Significant differences were found in para-aminohippurate clearance, G1 < G2, and higher renal vascular resistance values were observed in G1. Histological examination showed the greater vulnerability of kidneys exposed to sevoflurane alone (G1) with higher scores of vascular and tubular dilatation. There were vascular congestion and tubular vacuolization only in G1. Necrosis and signs of tubular regeneration did not differ in both groups. Conclusion. Treatment with glibenclamide attenuated acutely the renal histological changes after hemorrhage in rats under sevoflurane anesthesia.

Intrapleural analgesia after endoscopic thoracic sympathectomy

OBJETIVO: Comparar a analgesia tradicionalmente utilizada para simpatectomia videotoracoscópica à injeção intrapleural de ropivacaína em duas doses diferentes. MÉTODOS: Vinte e quatro pacientes foram distribuídos em três grupos semelhantes, e todos eles receberam dipirona endovenosa. O grupo A recebeu tramadol endovenoso e injeção intrapleural de solução salina. O grupo B recebeu injeção intrapleural de ropivacaína a 0,33%, e Grupo C ropivacaína a 0,5%. Os aspectos analisados foram: capacidade inspiratória, freqüência respiratória e dor. A dor foi avaliada no período pós-operatório por meio da escala visual analógica e durante o período de uma semana. RESULTADOS: Nos grupos A e B, a redução da capacidade inspiratória foi observada no período pós-operatório. Nas primeiras 12 horas de pós-operatório, apenas 12,5% dos pacientes nos grupos B e C apresentaram dor intensa em comparação a 25% no Grupo A. Na semana seguinte, apenas um paciente do grupo A apresentou dor leve, enquanto o restante relatou dor intensa. No Grupo B, metade dos pacientes apresentou dor intensa, e no Grupo C, apenas um apresentou intensa dor. CONCLUSÃO: A analgesia intrapleural com ropivacaína resultou em menos dor no pós-operatório tardio com os melhores resultados analgésicos nas doses mais altas, proporcionando um melhor padrão ventilatório.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Renal histology and immunohistochemistry after acute hemorrhage in rats under sevoflurane and ketoprofen effect

OBJETIVO: Investigar a influência do inibidor não-seletivo da ciclooxigenase, cetoprofeno (ceto) intravenoso, em alterações histológicas e dos níveis das citocinas renais - fator α de necrose tumoral (TNF- α) e interleucina 1 (IL-1) - após hemorragia de 30% da volemia (10%, três vezes, em intervalos de 10 min). MÉTODOS: Sob anestesia com sevoflurano (sevo), os grupos sevo e sevo+ceto (10 ratos cada) foram preparados cirurgicamente para leitura de pressão arterial média (PAM) e administração de solução de Ringer (5 mL/kg/h) e de cetoprofeno (1,5 mg/kg), no início da anestesia, no grupo sevo+ceto. Mediu-se temperatura retal continuamente. Os valores de temperatura e PAM foram observados antes da primeira hemorragia (T1), após a terceira hemorragia (T2) e 30 min após T2 (T3). Realizada nefrectomia bilateral nos dois grupos para análise histológica e imuno-histoquímica. RESULTADOS: Nos dois grupos, temperatura e PAM diminuíram com relação aos valores basais. Hipotermia foi mais acentuada no grupo sevo (p=0,0002). Necrose tubular foi mais frequente no grupo sevo (p=0,02). As citocinas estiveram igualmente presentes nos rins dos dois grupos. CONCLUSÃO: Cetoprofeno foi mais protetor no rim de rato durante anestesia com sevoflurano e hipovolemia, porém parece que TNF- α e IL-1 não estão envolvidas nessa proteção.