Ca2+- and Voltage-Activated K+ (BK) Channels in the Nervous System: One Gene, a Myriad of Physiological Functions.

BK channels are large conductance potassium channels characterized by four pore-forming α subunits, often co-assembled with auxiliary ß and γ subunits to regulate Ca2+ sensitivity, voltage dependence and gating properties. BK channels are abundantly expressed throughout the brain and in different compartments within a single neuron, including axons, synaptic terminals, dendritic arbors, and spines. Their activation produces a massive efflux of K+ ions that hyperpolarizes the cellular membrane. Together with their ability to detect changes in intracellular Ca2+ concentration, BK channels control neuronal excitability and synaptic communication through diverse mechanisms. Moreover, increasing evidence indicates that dysfunction of BK channel-mediated effects on neuronal excitability and synaptic function has been implicated in several neurological disorders, including epilepsy, fragile X syndrome, mental retardation, and autism, as well as in motor and cognitive behavior. Here, we discuss current evidence highlighting the physiological importance of this ubiquitous channel in regulating brain function and its role in the pathophysiology of different neurological disorders.

Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels.

In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey.

In the 1970s, calcium-activated potassium currents were recorded for the first time. In 10years, this Ca2+-activated potassium channel was identified in rat skeletal muscle, chromaffin cells and characterized in skeletal muscle membranes reconstituted in lipid bilayers. This calcium- and voltage-activated potassium channel, dubbed BK for "Big K" due to its large ionic conductance between 130 and 300 pS in symmetric K+. The BK channel is a tetramer where the pore-forming α subunit contains seven transmembrane segments. It has a modular architecture containing a pore domain with a highly potassium-selective filter, a voltage-sensor domain and two intracellular Ca2+ binding sites in the C-terminus. BK is found in the plasma membrane of different cell types, the inner mitochondrial membrane (mitoBK) and the nuclear envelope's outer membrane (nBK). Like BK channels in the plasma membrane (pmBK), the open probability of mitoBK and nBK channels are regulated by Ca2+ and voltage and modulated by auxiliary subunits. BK channels share common pharmacology to toxins such as iberiotoxin, charybdotoxin, paxilline, and agonists of the benzimidazole family. However, the precise role of mitoBK and nBK remains largely unknown. To date, mitoBK has been reported to play a role in protecting the heart from ischemic injury. At the same time, pharmacology suggests that nBK has a role in regulating nuclear Ca2+, membrane potential and expression of eNOS. Here, we will discuss at the biophysical level the properties and differences of mitoBK and nBK compared to those of pmBK and their pharmacology and function.

Isoflurane MAC determination in dogs using three intensities of constant-current electrical stimulation.

OBJECTIVES: To compare isoflurane minimum alveolar concentrations (MACs) in dogs determined using three intensities of constant-current electrical stimulation applied at the tail, and thoracic and pelvic limbs, and to compare isoflurane MACs obtained with all combinations of electrical stimulation and anatomic site with those obtained using the tail clamp as the noxious stimulus. STUDY DESIGN: Randomized trial. ANIMALS: Six mixed-breed, adult female dogs aged 1-2 years and weighing 11.1 ± 4.4 kg. METHODS: In each dog, MAC was determined by the bracketing method with the tail clamp (MACTAILCLAMP ), and three electrical currents (10 mA, 30 mA, 50 mA) at three anatomic sites (thoracic limb, pelvic limb, tail). Each MAC achieved with electrical stimulation was compared with MACTAILCLAMP using a mixed-model anova and Dunnett's procedure for multiple comparisons. The effects of current intensity and anatomic site on isoflurane MAC were tested using a mixed-model anova followed by Tukey's test for multiple comparisons (p < 0.05). RESULTS: Mean MACTAILCLAMP was 1.69%. MACs achieved with currents of 30 mA and 50 mA did not differ independently of anatomic site. When currents of 10 mA were applied to the tail and thoracic limb, resulting MACs were lower than those obtained using currents of 30 mA and 50 mA. Currents of 30 mA and 50 mA provided MACs that did not differ from those of MACTAILCLAMP , whereas a current of 10 mA achieved the same result only for the pelvic limb. CONCLUSIONS AND CLINICAL RELEVANCE: Isoflurane MAC is affected by current intensity and anatomic site. Current intensities of 30 mA and 50 mA provided consistent results when applied to the tail, and thoracic and pelvic limbs that did not differ from those obtained using the tail clamp. Consequently, they can be used in place of the tail clamp in MAC studies in dogs.

Exfoliative cytology as a tool for monitoring pre-malignant and malignant lesions based on combined stains and morphometry techniques.

BACKGROUND: Prevention and early diagnosis have the greatest potential for public health and are the most effective method in the long-term to control oral cancer. The aim was to apply PAP staining together with AgNOR staining and morphometric analysis in oral exfoliative cytology, to determine the sensitivity and specificity of these methods in the detection of malignant changes for the purposes of both initial population monitoring and follow-up. METHODS: AgNOR, Papanicolau, and morphometric tests were conducted in samples of patients with oral cancer, oral potentially malignant disorders and controls (opposite side of lesions). Specificity and sensitivity values for each stain method and the curve under ROC area were estimated. RESULTS: The diagnostic variables which allowed greatest accuracy in identifying malignancy relative to the healthy control were cluster (76.92%), satellite (75.64%), and total (90%). The diagnosis was seen to be associated with PAP and total AgNOR, total AgNOR and PAP, total AgNOR and satellites and clusters, and total AgNOR nuclear area/cytoplasmic area ratio. CONCLUSIONS: The total number of AgNOR is a reliable marker for detecting neoplastic cells; this method increases sensitivity and specificity by decreasing the likelihood of false negatives or positives, as the accuracy obtained was 90%. It is also a low-cost, non-invasive, simple methodology that can be recommended to help the early detection of oral cancer and monitoring of patients with a first diagnosis of cancer.

Estudio citomorfométrico de pacientes con cáncer y desórdenes potencialmente malignos de la cavidad bucal / Citomorphometric study of patients with cancer and potentially malignant disorders of the oral cavity

La detección temprana de lesiones bucales promete aumentar sobrevivencia y reducir la morbilidad de los pacientes que sufren esta condición. Un método alternativo para el examen de lesiones en la cavidad bucal, es la citología. Objetivo: valorar las relaciones del tamaño núcleo/citoplasma de células de mucosa bucal sana, de lesiones bucales potencialmente malignas y de cáncer bucal, obtenidas con citología exfoliativa utilizando citomorfometría. Material y método: Se realizó citología a 22 pacientes, de ambos sexos, con edades entre 23 y 81 años utilizando cytobrush. Las muestras se dividieron en tres grupos: 1) citologías de pacientes con lesiones de cáncer bucal (n=7); 2) citologías de pacientes con desórdenes bucales potencialmente malignos (leucoplasia y líquen) (n=15); 3) citologías del lado sano de pacientes con lesiones de cáncer y desórdenes bucales potencialmente malignos (grupo control) (n=15). Se seleccionaron 30 células de cada paciente y se midió el área nuclear (AN), la citoplasmática (AC) y se calculó la relación AN/AN. Se utilizó el Test de Kruskal Wallis y el Sofware estadístico Infostat. Resultados: No se encontraron diferencias significativas entre los tres grupos estudiados al valorar la relación AN/AC. Teniendo en cuenta el género, se observó que en las mujeres se diferenciaron significativamente las células del grupo control de las de los grupos de lesiones. En el género masculino se observaron diferencias significativas entre los tres grupos celulares. No hubo diferencias significativas entre los diferentes grupos etarios .Discusión: A pesar de las diferencias significativas entre los géneros, no es posible hacer una buena separación de los tres grupos de estudio, utilizando solamente citología exfoliativa.

Early detection of bucal lesions promises to increase survival and to reduce morbidity in patients suffering from this condition. An alternative method for examining lesions in the bucal cavity is cytology. Objective: To assess by cytomorphometry the relationship of size nucleus / cytoplasm of superficial cells from healthy bucal mucosa, from potentially malignant bucal disordes lesions and bucal cancer using exfoliative cytology. Material and methods: PAP smear was performed in 22 patients of both gender, aged between 23 and 81. Cytobrush was used. The samples were divided into three study groups: 1) smears of patients with bucal cancer lesions (n = 7), 2) smears of patients with potentially malignant bucal disordes lesions (n = 15), lesions considered were leukoplakia and lichens ; 3) (control group) (n=15): smears of the healthy side of patients with cancer and potentially malignant bucal disordes lesions.Thirty cells were selected for each patient and the nuclear area (NA), cytoplasmic area (CA) were measured and the ratio NA / CA was calculated. We used Kruskal Wallis and Statistical Software InfoStat. Results: No significant differences were found between the three groups studied the relationship NA / CA was assesed . When comparing cells from each of the three groups considering the gender of the patients separately, we found that in women differ significantly from the control group cells and groups of injuries, we could not discriminate between cells obtained from potentially malignant bucal disordes lesions and cancer lesions . In the male gender differences were significant among the three cell groups. Discusion: Despite the significant gender differences, we could not difference the three study groups using only exfoliative cytology.

Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain.

In Pseudomonas aeruginosa, quorum sensing constitutes a highly complex cell-to-cell communication system that, along with the cognate acylhomoserine lactone signals and regulators LasR and RhlR, modulates the production of virulence factors and a wide range of metabolic functions. In a previous paper, the authors reported that mismatch repair disruption in P. aeruginosa results in the spontaneous and reproducible emergence of defined morphological colony variants after a relatively short period of cultivation in an aerated rich medium, in contrast to the non-mutator parental strain, which does not display any kind of diversification under identical incubation conditions. One of the morphotypical variants, mS2, emerges at a high frequency and displays differences in virulence traits that could be regulated by major quorum-sensing regulators. The present study shows that mutS mS2 variants had defective LasR function due to simple but different point mutations along the lasR gene sequence, indicating that LasR inactivation is the main cause of mS2 phenotypic diversification. Moreover, it was determined that a non-functional LasR would confer a selective advantage in the late stationary phase, since viability was notably higher for mS2. Interestingly, in all mS2 variants analysed, no sequence alterations were found in the gacA and rhlR genes, suggesting that the selective pressures for GacA/RhlR and LasR were not the same and differed from those in other Pseudomonas species, which, when incubated in nutrient-rich liquid stationary-phase cultures, show specific high instability in the gacA-gacS genes.

Neuromuscular blocking properties of atracurium during sevoflurane or propofol anaesthesia in dogs.

OBJECTIVE: To quantify the neuromuscular blockade (NMB) produced by atracurium in either sevoflurane or propofol-anaesthetized dogs. ANIMALS: Twelve healthy, female adult mixed-breed dogs weighing 13 +/- 3 kg (range 10-22 kg). MATERIALS AND METHODS: Three doses of atracurium (0.1, 0.2 and 0.3 mg kg(-1)) were tested at 1-week intervals. Anaesthesia was induced with inhaled sevoflurane or intravenous propofol and maintained with end-tidal sevoflurane concentrations of 1.95% (1.25 x MAC) or propofol 0.6 mg kg(-1) minute(-1) respectively. Acceleromyography and train-of-four stimulation of the fibular nerve were used for the assessment of NMB. The percentage depression of the first twitch (T1) and the fourth to the first twitch ratio (T4/T1), the maximum degree of neuromuscular block achieved and surgical muscle relaxation were recorded. Before and during neuro muscular blockade (at 10 minute intervals) body temperature, ECG, arterial blood pressure, inspired and expired CO2 concentrations and SpO2 were recorded. RESULTS: Atracurium produced a dose-dependent duration of NMB in both propofol and sevoflurane-anaesthetized dogs. Duration of block was longer in dogs anaesthetized with sevoflurane. All studied doses of atracurium caused twitch depression > or =95% with little or no cardiovascular changes. CONCLUSIONS: Sevoflurane produces a clinically relevant potentiation of atracurium-induced NMB in dogs compared with propofol. CLINICAL RELEVANCE: Significant differences in the potentiation of NMB drugs are encountered with commonly used anaesthetics in the dog.

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs.

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.

Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa.

MutS is part of the bacterial mismatch repair system that corrects point mutations and small insertions/deletions that fail to be proof-read by DNA polymerase activity. In this work it is shown that the disruption of the P. aeruginosa mutS gene generates the emergence of diverse colony morphologies in contrast with its parental wild-type strain that displayed monomorphic colonies. Interestingly, two of the mutS morphotypes emerged at a high frequency and in a reproducible way and were selected for subsequent characterization. One of them displayed a nearly wild-type morphology while the other notably showed, compared with the wild-type strain, increased production of pyocyanin and pyoverdin, lower excretion of LasB protease and novel motility characteristics, mainly related to swarming. Furthermore, it was reproducibly observed that, after prolonged incubation in liquid culture, the pigmented variant consistently emerged from the mutS wild-type-like variant displaying a reproducible event. It is also shown that these P. aeruginosa mutS morphotypes not only displayed an increase in the frequency of antibiotic-resistant mutants, as described for clinical P. aeruginosa mutator isolates, but also generated mutants whose antibiotic-resistant levels were higher than those measured from spontaneous resistant mutants derived from wild-type cells. It was also found that both morphotypes showed a decreased cytotoxic capacity compared to the wild-type strain, leading to the emergence of invasive variants. By using mutated versions of a tetracycline resistance gene, the mutS mutant showed a 70-fold increase in the reversion frequency of a +1 frameshift mutation with respect to its parental wild-type strain, allowing the suggestion that the phenotypical diversity generated in the mutS population could be produced in part by frameshift mutations. Finally, since morphotypical diversification has also been described in clinical isolates, the possibility that this mutS diversification was related to the high frequency hypermutability observed in P. aeruginosa CF isolates is discussed.

Evaluation of different doses of propofol in xylazine pre-medicated horses.

OBJECTIVE: To characterize responses to different doses of propofol in horses pre-medicated with xylazine. ANIMALS: Six adult horses (five females and one male). METHODS: Each horse was anaesthetized four times with either ketamine or propofol in random order at 1-week intervals. Horses were pre-medicated with xylazine (1.1 mg kg-1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg-1 IV) or propofol (1, 2 and 4 mg kg-1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 10 and 15 minutes after anaesthetic induction (arterial pressure, respiratory rate, pH, PaO2, PaCO2 and O2 saturation). Anaesthetic induction and recovery were qualitatively and quantitatively assessed. RESULTS: Differences in the quality of anaesthesia were observed; the low dose of propofol resulted in a poorer anaesthetic induction that was insufficient to allow intubation, whereas the high dose produced an excellent quality of induction, free of excitement. Recorded anaesthesia times were similar between propofol at 2 mg kg-1 and ketamine with prolonged and shorter recovery times after the high and low dose of propofol, respectively (p < 0.05; ketamine, 38 +/- 7 minutes; propofol 1 mg kg-1, 29 +/- 4 minutes; propofol 2 mg kg-1, 37 +/- 5 minutes; propofol 4 mg kg-1, 50 +/- 7 minutes). Times to regain sternal and standing position were longest with the highest dose of propofol (32 +/- 5 and 39 +/- 7 minutes, respectively). Both ketamine and propofol reversed bradycardia, sinoatrial, and atrioventricular blocks produced by xylazine. There were no significant alterations in blood pressure but respiratory rate, and PaO2 and O2 saturation were significantly decreased in all groups (p < 0.05). CONCLUSION: The anaesthetic quality produced by the three propofol doses varied; the most desirable effects, which were comparable to those of ketamine, were produced by 2 mg kg-1 propofol.

Estudo experimental com o uso de quetamina associada ou näo à lidocaína para anestesia epidural caudal em eqüinos / An experimental study of caudal epidural anesthesia in horses using ketamine associated or not to lidocaine

Foram aplicadas, experimentalmente, anestesia epidural caudal com apenas quetamina ou associada à lidocaína para avaliar sua eficiência na espécie eqüina. Atualmente, existem evidências clínicas de interaçöes sinérgicas das açöes espinhais entre a combinaçäo de uma variada gama de fármacos. Estas podem evitar, ou ao menos reduzir, as açöes neurotóxicas que produzem a aplicaçäo isolada de um dos fármacos, que necessitam para isto doses e/ou concentraçöes superiores para obter a anestesia desejada. Para a realizaçäo deste experimento utilizamos seis cavalos de pesos e idades variadas, com os seguintes tratamentos: Grupo I: soluçäo salina; Grupo II: quetamina (1mg/kg); Grupo III: lidocaína (0,20 mg/kg); e Grupo IV: a associaçäo de quetamina (1 mg/kg)/lidocaína (0,20 mg/kg). Todos os grupos receberam volumes predeterminados e aplicados por via epidural. Para reduzir a variaçäo na resposta, o mesmo grupo de animais foi utilizado no experimento com um intervalo de uma semana entre as diferentes aplicaçöes. A anestesia foi avaliada mediante a estimulaçäo dolorosa, utilizando-se uma agulha 23G, e determinando o grau de resposta em uma escala de dor. Os tempos usados foram: basal e 2, 5, 10, 15 minutos e depois a cada 15 minutos, pós-administraçäo de quetamina, lidocaína e a associaçäo de quetamina/lidocaína, ou do grupo controle. Os resultados indicam que o tempo de anestesia e a eficiência da analgesia produzida pelo grupo quetamina/lidocaína administrada por via epidural foi superior a administraçäo destas drogas individualmente. Os efeitos cardiorrespiratórios foram mínimos em todos os grupos.

Estudo experimental com o uso de quetamina associada ou não à lidocaína para anestesia epidural caudal em eqüinos

Foram aplicadas, experimentalmente, anestesia epidural caudal com apenas quetamina ou associada à lidocaína paraavaliar sua eficiência na espécie eqüina. Atualmente, existem evidências clínicas de interações sinérgicas das ações espinhaisentre a combinação de uma variada gama de fármacos. Estas podem evitar, ou ao menos reduzir, as ações neurotóxicasque produzem a aplicação isolada de um dos fármacos, que necessitam para isto doses e/ou concentrações superiores paraobter a anestesia desejada. Para a realização deste experimento utilizamos seis cavalos de pesos e idades variadas, com osseguintes tratamentos: Grupo 1: solução salina; Grupo 11: quetamina (1 mg/kg); Grupo 111: lidocaína (0,20 mg/kg); e Grupo IV: aassociação de quetamina (1 mg/kg)/ lidocaína (0,20 mg/kg). Todos os grupos receberam volumes predeterminados e aplicadospor via epidural. Para reduzir a variação na resposta, o mesmo grupo de animais foi utilizado no experimento com umintervalo de uma semana entre as diferentes aplicações. A anestesia foi avaliada mediante a estimulação dolorosa, utilizandoseuma agulha 23G, e determinando o grau de resposta em uma escala de dor. Os tempos usados foram: basal e 2, 5, 1 O, 15minutos e depois a cada 15 minutos, pós-administração de quetamina, lidocaína e a associação de quetamina/lidocaína, oudo grupo controle. Os resultados indicam que o tempo de anestesia e a eficiência da

Utilizaçäo do isoflurano em macacos-prego (Cebus apella - Cebidae, Primata) / Use of isoflurane in capuchin monkeys (Cebus apella - Cebidae, Primata)

No presente estudo foram avaliadas as alteraçöes clínicas e anestesiológicas de macacos-prego (Cebus apella) submetidos a procedimento anestésico com isoflurano, nas concentraçöes de 1 a 1,5 CAM. Para tanto, 10 animais hígidos (7 machos e 3 fêmeas), pesando em média 3,1 ñ 0,8 kg, foram pré-medicados com quetamina e atropina e induzidos com isoflurano. A manutençäo anestésica foi feita com isoflurano a 1 CAM durante 30 minutos, seguindo-se 1,5 CAM por mais 30 minutos. Os parâmetros cardiovasculares e respiratórios foram mensurados a cada 5 minutos e os valores de pH e gases sangüíneos a cada 10 minutos, do tempo inicial (T0) ao final (T30), para cada concentraçäo do anestésico. Os valores obtidos foram comparados e analisados pelo teste näo-paramétrico de Wilcoxon (p < 0,05). Foi observada queda na temperatura corporal nas duas concentraçöes de anestésico. Näo foram observadas arritmias cardíacas, nem alteraçöes na pressäo arterial em ambas as concentraçöes, no entanto, houve diminuiçäo da freqüência cardíaca com 1,5 CAM. O isoflurano produziu depressäo dose-dependente no volume corrente e volume minuto, porém näo alterou significativamente a freqüência respiratória. Os valores de pH, pressäo parcial de O2 (PaO2) e pressäo parcial de CO2 (PaCO2) no sangue arterial e saturaçäo de O2 na hemoglobina (SaO2) nao sofreram modificaçäo significativa em ambas as concentraçöes de isoflurano

Use of isoflurane in capuchin monkeys (Cebus apella - Cebidae, Primata) / Utilização do isoflurano em macacos-prego (Cebus apella - Cebidae, Primata)

This study was performed in order to evaluate both clinical and anesthesiological responses during isoflurane anesthesia at 1 MAC and 1.5 MAC in capuchin monkeys. Therefore, ten healthy animals (7 males and 3 females), with an average weight of 3.1 ± 0.8 kg were premedicated with ketamine and atropine and induced with isoflurane. They were maintained with isoflurane at 1 MAC for 30 minutes and at 1.5 MAC for 30 minutes more. The cardiovascular and respiratory parameters were measured every 5 minutes and the pH, blood gases and oxygen saturation at each 10 minutes, from inicial (T0) to final time (T30) at both concentrations. The data were submitted to non-parametric Wilcoxon test statistical analysis (p 0.05). A decreased in body temperature was observed at both isoflurane concentrations. Although no cardiac arrhythmias could be observed, the heart rate decreased at 1.5 MAC. However there were no changes in blood arterial pressure at any concentration. Isoflurane produced a dose-dependent depression in both tidal and minute volumes, whereas there was no significant change in respiratory rate. The pH, PaO2, PaCO2 and SaO2 didnt change significantly at both concentrations.

No presente estudo foram avaliadas as alterações clínicas e anestesiológicas de macacos-prego (Cebus apella) submetidos a procedimento anestésico com isoflurano, nas concentrações de 1 a 1,5 CAM. Para tanto, 10 animais hígidos (7 machos e 3 fêmeas), pesando em média 3,1 ± 0,8 kg, foram pré-medicados com quetamina e atropina e induzidos com isoflurano. A manutenção anestésica foi feita com isoflurano a 1 CAM durante 30 minutos, seguindo-se 1,5 CAM por mais 30 minutos. Os parâmetros cardiovasculares e respiratórios foram mensurados a cada 5 minutos e os valores de pH e gases sangüíneos a cada 10 minutos, do tempo inicial (T0) ao final (T30), para cada concentração do anestésico. Os valores obtidos foram comparados e analisados pelo teste não-paramétrico de Wilcoxon (p 0,05). Foi observada queda na temperatura corporal nas duas concentrações de anestésico. Não foram observadas arritmias cardíacas, nem alterações na pressão arterial em ambas as concentrações, no entanto, houve diminuição da freqüência cardíaca com 1,5 CAM. O isoflurano produziu depressão dose-dependente no volume corrente e volume minuto, porém não alterou significativamente a freqüência respiratória. Os valores de pH, pressão parcial de O2 (PaO2) e pressão parcial de CO2 (PaCO2) no sangue arterial e saturação de O2 na hemoglobina (SaO2) não sofreram modificação significativa em ambas as concentrações de isofl

Cardiorespiratory effects of acepromazine, xylazine and midazolam under different isoflurane concentrations in dogs / Efeitos cardiorrespiratórios de acepromazina, xilazina e midazolam associados a diferentes concentrações de isoflurano

The cardiorespiratory effects of three tranquilizer-isoflurane combinations were evaluated in six, healthy, male dogs (weighting 25,0 ± 27,7kg). Acepromazine (0,1mg/kg iv) or xylazine (1.0mg/kg iv) or midazolam (0.2mg/kg iv) followed by isoflurane (1.0; 1.5 and 2.0 MAC) were administered to each animal. Cardiovascular and respiratory parameters were measured at 5, 10, 15 and 20 minutes. The results were submitted to statistical analysis (analysis of variance, Pearson linear correlation and compared with Duncan test, p 0.05). Cardiovascular depression was observed after acepromazine and xylazine administration. Xylazine produced highlier significantly respiratory depression than acepromazine. No significant changes were observed after midazolam administration at 1.0 and 1.5 MAC, but significant changes were observed on cardiovascular behavior at 2.0 MAC. We concluded that midazolam-isoflurane was the safest combination of this study, producing minimal depressant cardiopulmonary effects.

No sentido de estudar os efeitos cardiorrespiratórios de três combinações anestésicas, foram utilizados seis cães hígidos, machos (pesando 25,0 ± 27,7kg). Acepromazina (0.1mg/kg/iv) ou xilazina (1.0mg/kg/iv) ou midazolam (0.2mg/kg/iv), seguidas pela indução e manutenção com isoflurano (1.0; 1.5 e 2.0 CAM), foram administradas a cada animal. O grupo testemunho foi submetido à anestesia com isoflurano (1.0; 1.5 e 2.0 CAM). Os parâmetros cardiovasculares e respiratórios foram mensurados aos 5, 10, 15 e 20 minutos. Os resultados foram estatisticamente analisados (análise de variância, correlação linear de Pearson e comparados com o teste de Duncan). Foi observada depressão cardiovascular (p 0,05), após administração de acepromazina e de xilazina. Tanto a acepromazina quanto a xilazina produziram depressão respiratória, sendo esta última de maior intensidade. Foi observada depressão cardiovascular (p 0,05) somente após associação midazolam-isoflurano (2,0 CAM). Concluímos que a associação midazolam-isoflurano foi a mais segura, produzindo mínimo efeito depressor cardiorrespiratório.

Cardiorespiratory effects of acepromazine, xylazine and midazolam under different isoflurane concentrations in dogs / Efeitos cardiorrespiratórios de acepromazina, xilazina e midazolam associados a diferentes concentrações de isoflurano

The cardiorespiratory effects of three tranquilizer-isoflurane combinations were evaluated in six, healthy, male dogs (weighting 25,0 ± 27,7kg). Acepromazine (0,1mg/kg iv) or xylazine (1.0mg/kg iv) or midazolam (0.2mg/kg iv) followed by isoflurane (1.0; 1.5 and 2.0 MAC) were administered to each animal. Cardiovascular and respiratory parameters were measured at 5, 10, 15 and 20 minutes. The results were submitted to statistical analysis (analysis of variance, Pearson linear correlation and compared with Duncan test, p 0.05). Cardiovascular depression was observed after acepromazine and xylazine administration. Xylazine produced highlier significantly respiratory depression than acepromazine. No significant changes were observed after midazolam administration at 1.0 and 1.5 MAC, but significant changes were observed on cardiovascular behavior at 2.0 MAC. We concluded that midazolam-isoflurane was the safest combination of this study, producing minimal depressant cardiopulmonary effects.

No sentido de estudar os efeitos cardiorrespiratórios de três combinações anestésicas, foram utilizados seis cães hígidos, machos (pesando 25,0 ± 27,7kg). Acepromazina (0.1mg/kg/iv) ou xilazina (1.0mg/kg/iv) ou midazolam (0.2mg/kg/iv), seguidas pela indução e manutenção com isoflurano (1.0; 1.5 e 2.0 CAM), foram administradas a cada animal. O grupo testemunho foi submetido à anestesia com isoflurano (1.0; 1.5 e 2.0 CAM). Os parâmetros cardiovasculares e respiratórios foram mensurados aos 5, 10, 15 e 20 minutos. Os resultados foram estatisticamente analisados (análise de variância, correlação linear de Pearson e comparados com o teste de Duncan). Foi observada depressão cardiovascular (p 0,05), após administração de acepromazina e de xilazina. Tanto a acepromazina quanto a xilazina produziram depressão respiratória, sendo esta última de maior intensidade. Foi observada depressão cardiovascular (p 0,05) somente após associação midazolam-isoflurano (2,0 CAM). Concluímos que a associação midazolam-isoflurano foi a mais segura, produzindo mínimo efeito depressor cardiorrespiratório.