miR-148a regulation interferes in inflammatory cytokine and parasitic load in canine leishmaniasis.

Canine leishmaniasis (CanL) is a severe public health threat. Infected animals mediate transmission of the Leishmania protozoan to humans via the sandfly's bite during a blood meal. CanL progression depends on the degree of suppression of the immune response, possibly associated with microRNAs (miR), which can modulate mRNA translation into proteins and (consequently) regulate cell function. Increased miR-148a in splenic leukocytes (SL) of dogs with CanL was observed in previous studies, and in silico analysis, identified possible pathways involved in immune response regulation that are affected by this miR. Therefore, we evaluated the involvement of miR-148a in the regulation of TNF-α, IL-6, IL-12, IL-1ß, iNOS, MHCII, CD80, CD3, T-bet, and GATA-3 transcription factors and their relationship with parasite load in SL of dogs with CanL. Splenic leukocytes obtained from healthy and diseased dogs were transfected with miR-148a mimic and inhibitor oligonucleotides. After 48 hours, expression levels of MHCII, CD80, iNOS, CD3, T-bet, and GATA-3 were evaluated by flow cytometry, and concentrations of TNF-α, IL-12, IL-6, and IL-1ß were measured in culture supernatants by capture enzyme-linked immunosorbent assays. Transfection of SL with miR-148a mimics decreased iNOS levels in cells and TNF-α, IL-6, and IL-12 in the supernatants of cultured SL from CanL dogs. Interestingly, transfection with miR-148a inhibitor decreased parasite load in SL cells. These results suggest a direct or not regulatory role of this miR in the immune response to Leishmania infantum infection. We conclude that miR-148a can modulate immune responses by regulating inflammatory cytokines during CanL. Our results contribute to understanding the complex host/parasite interaction in CanL and could assist the development of treatments.

PD-1 and PD-L1 regulate cellular immunity in canine visceral leishmaniasis.

PD-1 is a negative costimulator of chronic infectious diseases In this study, we investigated the expression of PD-1 and its ligands in the spleen of dogs with visceral leishmaniasis and lymphoproliferative response to soluble antigen, in lymph node cells in the presence or absence of antibodies blocking PD-1 and its ligands. Our results showed expression of PD-1 and its ligands is higher after L. infantum infection and in the spleen of infected dogs, PD-1 blockage was able to restore the antigen-dependent lymphoproliferative response and regulated production of the cytokines IL-4 and IL-10 and NO production. We concluded that L. infantum infection modulates PD-1 and its ligands expression in canine VL and that blockage of PD-1 restores the immune response. Thus, blockage of PD-1 is a target for therapeutic drug development.

Cellular apoptosis and nitric oxide production in PBMC and spleen from dogs with visceral leishmaniasis.

Nitric oxide (NO) is involved in the death of the Leishmania parasite and regulation of apoptosis. We quantified the frequency of cells producing NO and its levels in the peripheral blood mononuclear cells (PBMC), leukocytes from spleen in Visceral Leishmaniasis (VL) symptomatic dogs and correlated NO levels with apoptosis and parasite load in the spleen. The percentage of NO+ cells and CD14+/NO+ was higher in PBMC and spleen cells in infected dogs than in controls. The levels of NO+ and CD14+/NO+ cells was higher in PBMC, but lower spleen of dogs infected than compared to control. Late apoptosis rates increased in PBMC and spleen of infected dogs compared to controls, and the NO levels and apoptosis not showed correlation. There was a positive correlation between the percentage of cells producing NO in the spleen and parasite load. The NO participates in the immune response in the canine VL, but it is not apoptosis inducer.

Stress hormones concentrations in the normal microenvironment predict risk for chemically induced cancer in rats.

Evidence show that stress hormones can influence cancer progression, but its role in carcinogenesis is poorly understood. In this study, we used a new method based on oral carcinogenesis model in rats to test the hypothesis that physiological levels of stress hormones in the normal tissue microenvironment would have significant predictive value for chemically induced cancer occurrence. Male Wistar rats were submitted to a tongue biopsy for measuring not-stress induced levels of norepinephrine, corticosterone, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in the tissue before carcinogenic induction. Rats were treated with the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogen for twenty weeks and then euthanized for microscopic evaluation of the tongue lesions. Increased pre-carcinogen norepinephrine concentrations and reduced basal corticosterone levels in the normal tissue microenvironment were predictive for oral squamous cell carcinoma (OSCC) occurrence. Likewise, increased pre-carcinogen norepinephrine levels in the normal microenvironment were associated a lower expression of pCDKN2a-p16 in OSCCs. Post-carcinogen levels of corticosterone and BDNF in oral leukoplakia tissues (precursor lesion of OSCC) and post-carcinogen corticosterone concentrations in OSCCs were higher than basal levels in the normal mucosa. Increased norepinephrine concentrations in OSCCs were associated to a greater tumor volume and thickness. Furthermore, higher levels of norepinephrine, ACTH and BDNF in OSCCs were associated to a lesser intensity of the lymphoplasmocytic infiltrate. This study shows that pre-carcinogen stress hormones levels in the normal microenvironment may be predictive for chemically induced cancer in rats. Moreover, chemical carcinogenesis can promote stressor-like effects with hormonal changes in the tissue microenvironment, which may be associated to tumor progression.

Bispectral index assessment in calves subjected to the continuous infusion of propofol combined with fentanyl administration / Indice biespectral em bezerros submetidos à infusão contínua de propofol associado ao fentanil

ABSTRACT: The aim of this study was to evaluate the bispectral index (BIS) effects in calves through continuous infusion of propofol with or without fentanyl. Eight Holstein male calves (ages from six to twelve months old) with an average weight of 123±18kg were used. All animals participated in both groups, always keeping a minimum interval of one week between the anesthetic procedures; the calves were randomly distributed between groups. Anesthesia was induced with an intravenous (IV) dose of propofol of 5mg kg-1 in control group (GP) or with propofol (4mg kg-1) associated with IV fentanyl 0.001mg kg-1(GF). All the calves were positioned in right lateral recumbency and were allowed to spontaneously breathe room air. Subsequently, the anesthesia was maintained by continuous infusion of propofol at the rate of 0.6mg kg-1 min-1 IV in GP, and associated with the infusion of fentanyl 0.001mg kg-1 hour-1 in GF. Measurements of BIS, signal quality index (SQI) and electromyography (EMG) were evaluated before anesthesia induction (TB), and at 15, 30, 45 and 60 minutes after the beginning of continuous drugs infusion (T15, T30, T45 and T60, respectively). The heart rate (HR), respiratory rate (f), end-tidal carbon dioxide tension (ETCO2) and recovery times were evaluated as well. No significant differences were observed between the groups in the BIS variables and the recovery time was longer in GF. Co-administration of propofol and fentanyl infusions, at the doses reported here, did not change the values of BIS in cattle, but delayed the recovery time.

RESUMO: O estudo teve por objetivo avaliar o índice biespectral (BIS) durante a infusão contínua de propofol associado ou não ao fentanil em bezerros. Foram utilizados oito animais machos entre seis e doze meses de idade, holandeses, com massa corporal média de 123±18kg. Todos os animais participaram de ambos os grupos, respeitando-se sempre um intervalo mínimo de uma semana entre uma anestesia e outra, sendo aleatoriamente distribuídos entre os grupos. A anestesia nos bezerros foi induzida com propofol na dose de 5mg kg-1; intravenoso (IV), grupo controle (GP) ou propofol 4mg kg-1 associado ao fentanil 0,001mg kg-1; IV, grupo fentanil (GF) e posicionados em decúbito lateral direito, onde permaneceram respirando espontaneamente ar ambiente. Ato contínuo, a manutenção anestésica foi realizada pela infusão contínua de propofol na taxa de 0,6mg kg-1 min-1; IV GP, associado ou não à infusão de fentanil 0.001mg kg-1 hora-1 GF. A mensuração das variáveis do BIS, índice de qualidade de sinal (IQS) eletromiografia (EMG), frequência cardíaca (FC), frequência respiratória (f) e dióxido de carbono ao final da expiração (ETCO2) foram avaliadas antes da indução anestésica no momento basal (MB), e 15, 30, 45 e 60 minutos após o início da infusão contínua dos fármacos (M15, M30, M45 e M60, respectivamente); o tempo de recuperação também foi avaliado. Não foram observadas diferenças significativas entre os grupos nas variáveis do BIS e o tempo de recuperação foi maior no GF. A co-administração das infusões de propofol e fentanil, nas doses utilizadas nesse estudo, não alterou os valores do BIS em bezerros, porém, prolongou o tempo de recuperação.

The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis.

Canine visceral leishmaniasis (CVL) is known to affect the cellular immunity of infected dogs, through impairing lymphoproliferation and microbicidal mechanisms. This study examined heme oxygenase-1 (HO-1) and its metabolites, oxidative stress and IL-10 levels in CVL and investigated correlations between these parameters. Additionally, the effects of HO-1 inhibition on the lymphoproliferative response and cytokine production in lymph node cells (LNCs) from infected dogs were evaluated. Forty-four dogs, 24 controls and 20 dogs with CVL were selected. Plasma and splenic levels of HO-1, haptoglobin, soluble CD163 receptor, ferritin and IL-10 were determined using capture ELISA. The HO-1 levels and relative gene expression in peripheral blood and bone marrow mononuclear cells were also determined. LNCs proliferation was evaluated with an HO-1 activator and with an HO-1 inhibitor, in the presence of the Leishmania infantum soluble antigen (SAgL), using flow cytometry. HO-1, IL-2, IFN-gamma and IL-10 were also determined in these cultures using capture ELISA. Infected dogs presented oxidative stress and increased HO-1 levels and relative gene expression, with correlation between oxidative stress and HO-1. The substances from heme metabolism and IL-10 were also elevated in the plasma and spleens of infected dogs. IL-10 and HO-1 levels were positively correlated with one another. Inhibition of HO-1 increased LNCs proliferation and decreased IL-10 and IL-2 production in the presence of SAgL. The increased HO-1 metabolism observed in CVL is probably associated with oxidative stress and increased IL-10, which could be one of the mechanisms responsible for inhibition of the lymphoproliferative response in sick dogs.

PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis.

Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-L1 (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-α, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-α and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-α concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-α. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF-α, and IL-4, as well as the parasitic load.

Bispectral index in calves anesthetized with xylazine, midazolam, ketamine, isoflurane and subjected to continuous rate infusion of lidocaine

PURPOSE: To assess the bispectral index (BIS) and recovery in calves anesthetized with xylazine, midazolam, ketamine and isoflurane and subjected to CRI of lidocaine. METHODS: Xilazine was administered followed by ketamine and midazolam, orotracheal intubation and maintenance on isoflurane using mechanical ventilation. Lidocaine (2 mg kg-1 bolus) or saline (0.9%) was administered IV followed by a CRI (100 µg kg-1 minute-1) of lidocaine (L) or saline (C). Were recorded BIS, heart rate (HR), mean arterial pressure (MAP) and rectal temperature (RT) before administration of premedication (TB) and 15 minutes after (TX), before administering lidocaine (T0) and 20, 40, 60 and 80 minutes after the start of the CRI . Time do sternal recumbency (SRE) and standing (ST) and plasma lidocaine concentration also evaluated. RESULTS: In both treatments BIS decreased significantly at all times compared to TB. TX was higher than the subsequent times. HR decreased from baseline at all times and decreased from T40 in L compared to C. SRE was higher in L compared to C. CONCLUSIONS: Bispectral index values were consistent with the degree of hypnosis of the animals. Lidocaine did not potentiate isoflurane anesthesia assessed by BIS in unstimulated calves anesthetized with constant E´Iso. Lidocaine increased the time to sternal recumbency. .

Effects of a continuous rate infusion of butorphanol in isoflurane-anesthetized horses on cardiorespiratory parameters, recovery quality, gastrointestinal motility and serum cortisol concentrations

PURPOSE: To assess the cardiorespiratory parametes, recovery, gastrointestinal motility and serum cortisol concentrations in horses anesthetized with isoflurane with or without a continuous rate infusion (CRI) of butorphanol for orchiectomy. METHODS: Twelve adult, intact, male horses weighing 332 ± 55 kg were included in the study. Xilazine was administered as premedication. Anesthesia was induced with ketamine and midazolam and maintained with isoflurane. Butorphanol (0.025 mg kg-1 bolus) or an equivalent volume of saline (0.9%) was given intravenously followed by a CRI of butorphanol (BG) (13 µg kg-1 hour-1) or saline (CG). Cardiorespiratory variables were recorded before (T0) and every 15 minutes for 75 minutes after the start of infusion. Serum cortisol concentration was measured at T0 and 60 minutes, and 30 minutes and 19 hours after the horse stood up. Recovery from anesthesia was evaluated using a scoring system. Gastrointestinal motility was evaluated before anesthesia and during 24 hours after recovery. RESULTS: There were no significant differences between groups in cardiopulmonary variables, or recovery scores or serum cortisol concentrations. A reduction in gastrointestinal motility was recorded for 60 minutes in BG. CONCLUSIONS: Continuous rate infusion of butorphanol in horses anesthetized with isoflurane did not adversely affect the cardiopulmonary variables monitored, or recovery scores. A small but statistically significant reduction in gastrointestinal motility occurred in the butorphanol group. .

Alteration of sFAS and sFAS ligand expression during canine visceral leishmaniosis.

Visceral leishmaniosis (VL) is caused by intracellular parasites of the genus Leishmania that affect humans and several animal species. Dogs are one of the main urban reservoirs of Leishmania infantum and play a central role in the transmission cycle to humans via sandflies. CD3+ cells apoptosis is involved in the immune response in VL. Dysregulation of apoptosis has been implicated in various disease states. An important regulator of apoptosis is the FAS-FAS-associated death domain protein (cluster of differentiation 95 - CD95) and FASL-FAS ligand protein (cluster of differentiation 178 - CD178) system involved in the down-regulation of immune reactions and in T cell-mediated cytotoxicity. FAS is a member of the tumor necrosis factor (TNF) receptor super family, which can be expressed in transmembrane or soluble forms. The soluble levels of FAS (sFAS), FASL (sFASL) and active Caspase-3, this last related to apoptotic cascade, were investigated in the spleen of 19 symptomatic dogs presenting moderate VL and 6 healthy dogs, determined by ELISA assay. The splenic parasite load was determined by real-time PCR monitoring of amplification of the intergenic internal transcribed spacer (ITS1) gene of parasite rRNA. sFAS levels were lower (p<0.05). sFASL and active Caspase-3 levels were higher (p<0.05) in dogs with VL compared with controls. Negative correlation was observed between parasite burden and sFASL levels. The increase in sFASL could be related to the mechanism involved in the elimination of the parasite.

Effects of continuous rate infusion of butorphanol in isoflurane-anesthetized calves

PURPOSE: To assess the hemodynamic changes and bispectral index (BIS) following administration of a continuous rate infusion (CRI) of butorphanol in isoflurane-anesthetized calves. METHODS: Eight calves weighing 110 ± 12 kg were included in the study. Anesthesia was induced with 5% isoflurane in O2 delivered via face mask and maintained with end-tidal concentration of 1.4%. IPPV was set to a peak inspiratory airway pressure of 15 cmH2O and respiratory rate of six breaths minute-1. Forty minutes after the start of anesthetic maintenance, 0.1 mg kg-1butorphanol was administered intravenously, followed by a CRI of 20 µg kg-1 minute-1. Hemodynamic variables and BIS were recorded before butorphanol administration (T0), and at 10, 20, 40 and 80 minutes following the CRI. Anesthesia was discontinued after the last recording and the calves were allowed to recover. The time to sternal recumbency (SRE) and standing (ST) were evaluated. RESULTS: There were no significant differences between the moments in all hemodynamic variables and BIS. The time to SRE and ST was 9 ± 5 and 14 ± 7 minutes, respectively. CONCLUSION: The continuous rate infusion did not produce clinically relevant changes in hemodynamic or bispectral index values compared to baseline in mechanically ventilated and unstimulated calves anesthetized at 1.4% isoflurane. .

CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp.

Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion.

Hemodinâmica de diferentes frações inspiradas de oxigênio em cães submetidos à infusão contínua de propofol sob ventilação espontânea / Hemodyinamic effects of several inspired oxygen fractions in spontaneously breathing dogs submitted to continuous infusion of propofol

Avaliaram-se os efeitos do fornecimento de diferentes frações inspiradas de oxigênio (FiO2) sobre os parâmetros hemodinâmicos em cães submetidos à infusão contínua de propofol e mantidos em ventilação espontânea. Foram utilizados oito cães, os quais foram empregados em cinco grupos com diferentes FiO2, G100 (FiO2 = 1), G80 (FiO2 = 0,8), G60 (FiO2 = 0,6), G40 (FiO2 = 0,4) e G20 (FiO2 = 0,21), respeitando-se um intervalo de dez dias entre cada procedimento anestésico. Os animais foram induzidos e mantidos sob anestesia com propofol na dose de 0,7mg kg-1 min-1 e, após a intubação orotraqueal, iniciou-se o fornecimento de oxigênio conforme a FiO2 determinada para cada grupo. As primeiras mensurações, da freqüência cardíaca (FC), das pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM), da resistência vascular periférica e pulmonar (RPT e RPV), do débito cardíaco (DC); da pressão venosa central (PVC), da pressão média da artéria pulmonar (PMAP), da pressão média capilar pulmonar (PMCP), da pressão parcial de oxigênio (PaO2) e do dióxido de carbono (PaCO2) no sangue arterial, foram efetuadas 30 minutos após o início da infusão do anestésico (M0), seguidas de intervalos de 15 minutos (M15, M30, M45 e M60). Os dados numéricos obtidos foram submetidos à Análise de Variância, seguida pelo teste Tukey (P<0,05). Os parâmetros hemodinâmicos não apresentaram diferenças significativas ao longo do tempo e entre os grupos. Os resultados obtidos permitiram concluir que as variáveis hemodinâmicas não são afetadas pelo emprego de diferentes FiO2.

The effects of several inspired oxygen fractions (FiO2) in hemodynamics parameters in spontaneously breathing dogs submitted to continuous infusion of propofol were evaluated. Eight adult mongrel dogs were studied and the animals underwent five anesthesias. In each procedure the patient was submitted to a different FiO2, thereby resulting in five groups, namely: G100 (FiO2 = 1), G80 (FiO2 = 0.8), G60 (FiO2 =0.6), G40 (FiO2 = 0.4), and G20 (FiO2 = 0.21). The dose of propofol was sufficient to abolish protector reflex and ensure endotracheal intubation, followed by immediate continuous infusion of that drug (0.7mg kg-1 min-1). The initial measurement (M0) of heart rate (HR); systolic (SAP), diastolic (DAP) and mean pressure (MAP), systemic (SVR) and pulmoary vascular resistance (PVR), cardiac output (CO); central venous pressures (CVP); mean pulmonary pressure (MPAP); pulmonary capillary wedge pressure (PCWP), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) were recorded thirty minutes after the beginning of propofol infusion. Additional recordings were performed at each 15-minute interval during 60 minutes (M15, M30, M45, and M60). Numeric data were submitted to Analysis of Variance followed by Tukey Test (P<0.05). Significant values of hemodynamic parameters were not recorded neither during the experiment period nor among the groups. In conclusion, different FiO2 does not impair hemodynamic parameters.

Hemogasometria e variáveis cardiopulmonares após administração do butorfanol em cães anestesiados pelo desfluorano sob ventilação espontânea / Acid-base and cardiopulmonary effects after butorphanol administration in spontaneously breathing dogs anesthetized by desflurane

Este experimento teve por objetivos avaliar as possíveis alterações cardiopulmonares e hemogasométricas decorrentes do uso do butorfanol em cães submetidos à anestesia pelo desfluorano sob ventilação espontânea. Para tal, foram utilizados vinte cães adultos, clinicamente saudáveis, pesando 12±3kg. Os animais foram distribuídos igualmente em dois grupos, GS e GB, e induzidos à anestesia com propofol (8,4±0,8mg kg-1, IV), intubados e submetidos à anestesia inalatória pelo desfluorano (10V por cento). Decorridos 40 minutos da indução, foi administrado aos animais do GS 0,05mL kg-1 de solução fisiológica a 0,9 por cento (salina), enquanto que, no GB, foi aplicado butorfanol na dose de 0,4mg kg-1, ambos pela via intramuscular. As observações das variáveis freqüências cardíaca (FC) e respiratória (f), pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), pH arterial (pH), pressão parcial de oxigênio no sangue arterial (PaO2), pressão parcial de dióxido de carbono no sangue arterial (PaCO2), déficit de base (DB), bicarbonato (HCO3) e saturação de oxigênio na hemoglobina (SatO2) tiveram início imediatamente antes da aplicação do opióide ou salina (M0). Novas mensurações foram realizadas 15 minutos após a administração do butorfanol ou salina (M15) e as demais colheitas foram realizadas a intervalos de 15 minutos, por um período de 60 minutos (M30, M45, M60 e M75). Os dados numéricos dessas variáveis foram submetidos à Análise de Perfil (P<0,05). A freqüência cardíaca apresentou alteração no GB, com média de M0 maior que as demais. As PAS, PAD e PAM, assim como a f e o pH, apresentaram valores menores após a administração do opióide no GB, em comparação ao GS. A PaO2 apresentou discretas alterações, entretanto sem significado clínico, enquanto que a PaCO2 e o DB apresentaram valores de M0 menores que os demais após a aplicação do butorfanol. Os resultados obtidos permitem concluir que a administração do butorfanol em...

The cardiopulmonary and acid-base effects of butorphanol in desflurane anesthetized dogs breathing spontaneously were evaluated. Twenty adult healthy, male and female dogs were used. They were separated into two groups of 10 animals each (GS and GB). Anesthesia was induced with propofol (8.4±0.8mg kg-1 IV) and maintained with desflurane (10V percent). After 40 minutes of induction, the animals from GS received saline solution at 0.9 percent (0.05mL kg-1) and from GB received butorphanol (0.4mg kg-1), both applied intramuscularly. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures; arterial blood pH (pH), arterial partial pressure of O2 (PaO2) and arterial partial pressure of CO2 (PaCO2); base deficit (BD), arterial oxygen saturation (SaO2) and bicarbonate ion concentration (HCO3) were measured. The measurements were taken immediately before the application of the agents (M0). Serial measurements were carried out at 15 minutes intervals after the administration of butorphanol or saline up to 75 minutes (M15, M30, M45, M60 and M75). Data were submitted to Profile Analysis (P<0.05). After butorphanol administration HR, SAP, DAP and MAP decreased significantly. PaO2 had discreet alterations, however without clinical meaning. RR and pH decreased after butorphanol administration while PaCO2 increased significantly. It was possible to conclude that butorphanol administration in desflurane anesthetized dogs produced reduction in the averages of heart rate and arterial pressure and relatively to the respiratory parameters, the opioid produced hypoventilation in spontaneously breathing dogs.

Efeitos de diferentes frações inspiradas de oxigênio sobre a dinâmica respiratória em cães submetidos à infusão contínua de propofol e mantidos em ventilação espontânea / Effects of several inspired oxygen fractions on the respiratory dynamics in spontaneously breathing dogs undergoing continuous infusion of propofol

Avaliaram-se os efeitos do fornecimento de diferentes fraçõesinspiradas de oxigênio (FiO2) sobre a dinâmica respiratória em cãessubmetidos a infusão contínua de propofol e mantidos em ventilaçãoespontânea. Oito cães foram submetidos a cinco anestesiasdiferenciando uma da outra pela FiO2 fornecida. Formaram-se cincogrupos denominados G100 (FiO2 = 1), G80 (FiO2 = 0,8), G60 (FiO2 = 0,6), G40 (FiO2 = 0,4) e G20 (FiO2 = 0,21). Os animais foraminduzidos à anestesia com propofol na dose necessária para intubação,e ato contínuo iniciou-se a infusão do fármaco e o fornecimento deoxigênio conforme a FiO2 determinada para cada grupo. As primeirasmensurações foram efetuadas 30 minutos após o início da infusãodo anestésico (M0), em seguida em intervalos de 15 minutos (M15,M30, M45 e M60). Os dados numéricos obtidos foram submetidosa Análise de Variância, seguida pelo teste Tukey (p<0,05). Os valoresregistrados de saturação de oxihemoglobina (SpO2) e SaO2 foramsignificativamente menores para G20, enquanto que a pressão parcialde oxigênio no sangue arterial (PaO2) variou conforme a fração deoxigênio fornecida. Para a pressão parcial de dióxido de carbono nosangue arterial (PaCO2) foram registradas diferenças em M30, no qualG100 apresentou médias superiores a G20. Conclui-se que ofornecimento de oxigênio a 100%, 80% e 21% devem ser evitados,pois proporciona prejuízos significativos ao sistema respiratório decães anestesiados com infusão contínua de propofol na dose de 0,7mg/kg/min sob ventilação espontânea.

Efeitos cardiorrespiratórios do butorfanol em cães pré-tratados ou não pela levomepromazina / Cardiopulmonary effects of butorphanol in dogs treated with levomepromazine

Objetivou-se com este experimento avaliar os efeitos do butorfanol precedido ou não pela levomepromazina sobre a freqüência cardíaca (FC), as pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM, respectivamente), a freqüência respiratória (f), a concentração de dióxido de carbono ao final da expiração (ETCO2), a saturação da oxihemoglobina (SpO2), o volume corrente (VC) e o volume minuto (VM), em cães. Para tal, foram empregados vinte animais adultos, clinicamente saudáveis, distribuídos igualmente em dois grupos (GC e GL). Ao GC administrou-se solução salina a 0,9 por cento (Controle), no volume de 0,2mL kg-1, pela via intravenosa (IV). Decorridos 15 minutos, administrou-se butorfanol na dose de 0,3mg kg-1 pela mesma via. Aos animais do GL foi adotada a mesma metodologia, porém substituindo-se a solução salina pela levomepromazina na dose de 1mg kg-1. As medidas das variáveis cardiorrespiratórias iniciaram-se imediatamente antes da aplicação dos fármacos (M1). Novas mensurações foram realizadas 15 minutos após a administração da solução salina a 0,9 por cento ou levomepromazina (M2) e 10 minutos após a administração de butorfanol (M3). As demais colheitas foram realizadas a intervalos de 10 minutos, durante 30 minutos (M4, M5 e M6, respectivamente). Os dados numéricos colhidos foram submetidos à Análise de Variância (ANOVA), seguida pelo teste de Tukey (p<0,05) para as comparações das médias. O emprego do butorfanol promoveu diminuição significativa das freqüências cardíaca e respiratória e do volume minuto no grupo previamente tratado pela levomepromazina; entretanto, essas alterações foram discretas, não comprometendo os demais parâmetros circulatórios e respiratórios.

This work was aimed at evaluating the effects of the butorphanol in dogs preceded or not buy levomepromazine on heart rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP and MAP, respectively), respiratory rate (RR), end tidal CO2 (ETCO2), oxyhemoglobin saturation (SpO2), minute volume (MV) and tidal volume (TV). Twenty adult animals, clinically health were randomly distributed in two groups with ten animals each one (CG and LG). The first one received intravenous administration (IV) of 0.2mL kg-1 of saline solution at 0.9 percent (control). After 15 minutes, 0.3mg kg-1 of butorphanol was administrated by the same way. The same methodology was adopted to the GL animals, however, the saline solution at 0.9 percent was substituted to 1mg kg-1 of levomepromazine. The cardiorespiratory parameters were measured before the administration of the drugs (M1). New measurements were carried 15 minutes after saline or levomepromazine administration (M2), and 10 minutes after butorphanol administration (M3). The next M4, M5 and M6 were carried out through at intervals of 10 minutes during 30 minutes. The numeric data were submitted to the Analysis of Variance (ANOVA) followed by Tukey test (p<0.05) for the comparisons of the averages. The butorfanol promoted significative decreasing on cardiac and respiratory rate and reduction on minute volume after administration of levomepromazine. However these changes were discreet and did not produce depression on other circulatory and breathing parameters.

Efeitos do óxido nitroso sobre parâmetros cardiovasculares e respiratórios em cães anestesiados com diferentes doses de desfluorano / Effects of nitrous oxide on cardiovascular and respiratory parameteres in dogs anesthetized with different concntrations of desflurane

Estudaram-se possíveis alterações cardiovasculares e respiratórias provocadas pelo desfluorano associado ou não ao Np.Para tal, utilizaram-se 30 cães adultos, machos ou fêmeas, sem raça definida e hígidos, distribuídos em dois grupos de igual número denominados GD e GDN. Os animais do GD receberam propofol para a indução anestésica e imediatamente após, 11, 5V% de desfluorano diluído em 100% de O2 Decorridos 30 minutos do início da administração do anestésico volátil, o balão reservatório foi esvaziado, reduziu-se a concentração em 1,44V% e o circuito anestésico foi saturado com a nova mistura. Repetiu-se o protocolo em intervalos de 15 minutos, até atingir a concentração anestésica equivalente a 8,64V%. O GDN foi submetido ao mesmo protocolo, porém substituiu-se o fluxo diluente por 30% O2 e 70% Np. Foram mensuradas as freqüências cardíaca (FC) e respiratória (FR), pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM), concentração de dióxido de carbono ao final da expiração (ETC02) e saturação de oxi-hemoglobina (Sp02). As mensurações foram realizadas antes da indução anestésica (MO), aos 30 (M30), 45 (M45) e 60 (M60) minutos de anestesia. Observou-se aumento da FC com discreta redução da PA e diminuição da FR com conseqüente aumento da ETC02, coincidindo com a maior dose de desfluorano administrada. Concluiu-se que maiores concentrações de desfluorano induzem alterações discretas nas variáveis testadas e que a adição de Np na mistura diluente não determina interferências significativas nos achados)

Efeitos cardiorrespiratórios da buprenorfina em cães anestesiados pelo desfluorano / Cardiorespiratory effects of buprenorphine in dogs anesthetized with desflurane

Objetivou-se, com este estudo, avaliar os efeitos da buprenorfina sobre variáveis cardiovasculares e respiratórias em cães durante anestesia com desfluorano. Para tanto, foram utilizados 20 cães adultos, distribuídos em dois grupos (GB e GC). A anestesia foi induzida com propofol (8mg kg-1 IV) e em seguida os animais foram intubados com sonda de Magill, a qual foi conectada ao aparelho de anestesia para administração de desfluorano (1,5 CAM). Após 30 minutos, foi aplicado no GB buprenorfina (0,02mg kg-1) e no GC solução de NaCl à 0,9 por cento (0,05ml kg-1). Avaliaram-se: freqüências cardíaca e respiratória (FC e ¦); pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM); débito cardíaco (DC); pressão venosa central (PVC); e as variáveis hemogasométricas pH, PaCO2, PaO2, HCO3, SatO2 e DB. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (MO), 15 minutos após a administração do opióide ou placebo (M15), e a cada 15 minutos após Ml5 (M30, M45, M60 e M75). A avaliação estatística dos dados foi efetuada por meio de Análise de Perfil (P<0,05). Houve discreta redução da FC no GB, enquanto as outras variáveis cardiovasculares não tiveram redução significativa. A ¦ e o pH tiveram reduções no GB, enquanto a PaCO2 esteve aumentada. Concluiu-se que a inclusão da buprenorfina durante anestesia inalatória pelo desfluorano determina discretas alterações cardiovasculares, bem-como potencializa a hipoventilação promovida pelo desfluorano, com a manifestação de hipercapnia, o que não contra-indica o seu uso em pacientes estáveis.

Propofol ou sevofluorano sobre variáveis hemodinâmicas em cães submetidos à administração subaracnóidea de iohexol / Propofol or sevoflurane upon hemodynamic variables in dogs submitted to subarachnoid administration of iohexol

Avaliaram-se os efeitos do propofol ou sevofluorano sobre variáveis hemodinâmicas, em cães submetidos à mielografia. Para tanto, utilizaram-se trinta animais distribuídos em dois grupos de igual número, denominados GP e GS. Os animais do GP receberam propofol (10mg kg-1) por via intravenosa para intubação orotraqueal, e imediatamente após, administrou-se continuamente, por meio de bomba de infusão, propofol (0,55 ± 0,15mg kg-1 min-1). Decorridos 30 minutos, foi colhido liquor na cisterna magna e o meio de contraste iohexol foi injetado. No GS empregou-se a mesma metodologia adotada para o GP, utilizando indução anestésica pela administração de sevofluorano a 2,5 CAM, com o uso de máscara naso-oral vedada e manutenção com 1,5 CAM. As variáveis estudadas foram freqüência cardíaca (FC), pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM, respectivamente), débito cardíaco (DC), volume sistólico (VS), pressão venosa central (PVC), freqüência respiratória (f), concentração de dióxido de carbono ao final da expiração (ETCO2) e saturação de oxihemoglobina (SpO2). As mensurações das variáveis foram realizadas imediatamente após a colheita do liquor (M1), logo após a aplicação de iohexol (M2), seguida das demais em intervalos de 10 minutos, durante uma hora. Utilizazou-se a Análise de Variância (ANOVA) seguida pelo teste F como métodos estatísticos, considerando p<0,05. Houve redução da pressão arterial em ambos os grupos, sendo menos intensa no grupo que recebeu propofol. No GS, observou-se redução da FC e aumento do DC e do VS. Referente a ETCO2 as médias do GP foram superiores às do GS. Os resultados obtidos permitiram concluir que tanto o propofol como o sevofluorano não promovem alterações hemodinâmicas que comprometam a técnica de mielografia.

Cardiopulmonary and acid-base effects of desflurane and sevoflurane in spontaneously breathing cats.

The cardiopulmonary effects of desflurane and sevoflurane anesthesia were compared in cats breathing spontaneously. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressures; partial pressure of end tidal carbon dioxide (PETCO2), arterial blood pH (pH), arterial partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2); base deficit (BD), arterial oxygen saturation (SaO2) and bicarbonate ion concentration (HCO3) were measured. Anesthesia was induced with propofol (8+/-2.3mg/kg IV) and maintained with desflurane (GD) or sevoflurane (GS), both at 1.3 MAC. Data were analyzed by analysis of variance (ANOVA), followed by the Tukey test (P<0.05). Both anesthetics showed similar effects. HR and RR decreased when compared to the basal values, but remained constant during inhalant anesthesia and PETCO2 increased with time. Both anesthetics caused acidemia and hypercapnia, but BD stayed within normal limits. Therefore, despite reducing HR and SAP (GD) when compared to the basal values, desflurane and sevoflurane provide good stability of the cardiovascular parameters during a short period of inhalant anesthesia (T20-T60). However, both volatile anesthetics cause acute respiratory acidosis in cats breathing spontaneously.