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Papers by Shirley Burburan

A68. TISSUE REMODELING IN THE LUNG, 2012

Background: Sevoflurane is an anesthetic routinely used and there are no studies disclosing its e... more Background: Sevoflurane is an anesthetic routinely used and there are no studies disclosing its effects on a chronically inflamed and remodeled airway as that found in asthma. The present study aimed to define the respiratory effects of sevoflurane in a model of chronic allergic asthma. Methods: Thirty-six BALB/c mice (20-25 g) were randomly divided into four groups. In OVA groups, mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. In SAL groups, mice received saline using the same protocol. Twenty-four hours after the last challenge, the animals were anesthetized with pentobarbital sodium (PENTO, 20 mg/kg i.p.) or sevoflurane (SEVO, 1 MAC). Lung static elastance (Est), resistive (ΔP1) and viscoelastic/inhomogeneous (ΔP2) pressures were analyzed by end-inflation occlusion method. Lungs were fixed and stained for histopathological analysis. Results: OVASEVO group showed lower ΔP1 (38%), ΔP2 (24%), and Est (22%) than animals of OVAPENTO group (p < 0.0...

ABSTRACT Recent investigations reported that sevoflurane anaesthesia has anti-inflammatory effect... more ABSTRACT Recent investigations reported that sevoflurane anaesthesia has anti-inflammatory effects in sepsis. However, there are no studies, so far, examining the anti-inflammatory effects of sevoflurane in a chronically inflamed and remodeled airway, such as that found in asthma. For this purpose, lung histology and gene expression of pro- and anti-inflammatory cytokines were analysed. Thirty-six BALB/c mice (20-25 g) were randomly divided into four groups (n=9). In OVA groups, mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. In SAL groups, mice received saline using the same protocol. Twenty-four hours after the last challenge, the animals were anesthetized with pentobarbital sodium (PENTO, 20 mg/kg i.p.) or sevoflurane (SEVO,1MAC). Lung static elastance, airway resistance, and viscoelastic/inhomogeneous pressure were analysed by end-inflation occlusion method. Left lungs were fixed and stained for histological analysis. In addition, we measured tumour necrosis factor (TNF)-a, interleukin (IL)-6, macrophage migration inhibitory factor (MIF), interferon (IFN)-γ, and tumour growth factor (TGF)-β mRNA expression in right lung tissue using ribonuclease protection assay (RPA). Animals in the OVASEVO group showed lower airway resistance, viscoelastic pressure and static elastance than mice in the OVAPENTO group. We observed greater airway dilation (20%) and a lower degree of alveolar collapse (22%) in the OVASEVO compared with OVAPENTO group. Airway resistance was lower (26%) and airway diameters larger (13%) in the SALSEVO compared with SALPENTO group. Detailed quantitation by densitometry analysis showed that lungs mRNA for TNF-a and IL-6 were significantly lower in OVASEVO than OVAPENTO group, however IFN-γ and TGF-β were similar in both OVA groups. In conclusion, sevoflurane anaesthesia acted in airway level and lung periphery probably by reducing the inflammatory response in chronic allergic asthma.

ABSTRACT O papel protetor dos anestésicos voláteis na síndrome do desconforto respiratório aguda ... more ABSTRACT O papel protetor dos anestésicos voláteis na síndrome do desconforto respiratório aguda vem sendo intensamente estudado, entretanto, até o presente, nenhum estudo avaliou seus efeitos imunomodulatórios na asma. O presente estudo analisou os efeitos dos anestésicos isoflurano, halotano e sevoflurano sobre os aspectos morfofuncionais pulmonares, bem como sobre o processo inflamatório e o estresse oxidativo na asma alérgica experimental. Para tal, 56 camundongos BALB/c foram sensibilizados e desafiados com ovalbumina e anestesiados com isoflurano (ISO), o halotano (HALO), sevoflurano (SEVO) ou pentobarbital sódico (CTRL) durante 60 minutos. Foram avaliadas a resistência das vias aéreas, a elastância estática do pulmão e a morfometria pulmonares. Além disso, quantificou-se a expressão de mediadores envolvidos na inflamação [fator de necrose tumoral (TNF)-α], fibrogênese [fator transformador do crescimento (TGF)-β], angiogênese [fator de crescimento vascular endotelial (VEGF)] e também no processo oxidativo [fator nuclear eritróide 2 relacionado ao fator 2 (Nrf2), Sirtuína (Sirt)-1, catalase e glutationa peroxidase (GPx)]. ISO, HALO e SEVO reduziram a resistência das vias aéreas (-37%, -35% e -52%), a elastância estática do pulmão (-16%, -19% e -22%) e a fração de alvéolos colapsados (-25%, -48% e -57%) em relação ao CTRL (p < 0,001). SEVO diminuiu também a broncoconstrição (-22%), a infiltração de células polimorfonucleares (-39%) e a expressão de TNF-α (-71%), TGF-β (-63%), VEGF (-50%), Sirt-1 (-80%), catalase (-76%) e GPx (-69%) e aumentou significativamente o Nrf2 (+579%). A anestesia com sevoflurano melhorou a função pulmonar e a fração de área de alvéolos colapsados, reduziu processo inflamatório e minimizou o stress oxidativo no presente modelo murino de asma.

ABSTRACT RATIONALE: Anesthetic management in asthmatic patients has been focused in avoiding bron... more ABSTRACT RATIONALE: Anesthetic management in asthmatic patients has been focused in avoiding bronchoconstriction and inducing bronchodilation. However, since asthma has been defined as a clinical syndrome characterized by an inflammatory process that extends beyond the central airways to the distal airways and lung parenchyma, a rational choice of anesthetic agents and procedures is mandatory. Volatile anesthetic agents have been routinely used in asthma patients, nevertheless, there are no studies comparing their effects on a chronically inflamed and remodeled airway as that found in asthma. The present study aimed to compare the respiratory effects of halothane, isoflurane and sevoflurane in a model of chronic allergic asthma. For this purpose, pulmonary mechanics, airway responsiveness and lung morphometry were analyzed to determine whether the physiological modifications reflected underlying morphological changes. METHODS: Fifty-six BALB/c mice (20-25 g) were randomly divided into eight groups. In asthma groups, mice were sensitized and repeated challenged with ovalbumin. SAL groups received saline using the same protocol. Twenty-four hours after the last challenge, animals were anesthetized with either halothane (Halo), isoflurane (Iso), sevoflurane (Sevo) or control drug thiopental sodium (Control). Lung static elastance (Est), resistive (P1) and viscoelastic/inhomogeneous (P2) pressures were analyzed by end-inflation occlusion method. Lungs were fixed and stained for histopathological analysis. RESULTS: Asthma animals anesthetized with halothane, isoflurane and sevoflurane resulted in lower P1 (34%, 36%, and 52%), P2 (48%, 46%, and 47%), and alveolar collapse (48%, 25%, and 59%) compared to the Control group. Est was more reduced in Asthma-Halo (20%) and Asthma-Sevo (22%) groups than Asthma-Control. Furthermore, sevoflurane led to greater airway dilation (24%) compared to Control. CONCLUSION: Among these volatile anesthetic agents, sevoflurane acted on central and distal airways reducing airway resistance, viscoelastic pressure and static elastance in the present model of chronic allergic asthma.

In the present study, we aimed to define the immunomodulatory effects of sevoflurane anesthesia i... more In the present study, we aimed to define the immunomodulatory effects of sevoflurane anesthesia in experimental chronic allergic asthma. Twelve BALB/c mice were divided into two groups, sensitized and challenged with ovalbumin (ASTHMA) or saline (CONTROL). Animals
were then anesthetized with either sevoflurane (SEVO) or pentobarbital sodium (PENTO) and mRNA expression of cytokines (TNF-α, IL-6, TGF-β, IFN-γ, and MIF) was measured in lung tissue. TNF-α, IL-6, TGF-β and IFN-γ expressions were lower in ASTHMA-SEVO than ASTHMA-PENTO
group with no significant changes in MIF levels. In conclusion, sevoflurane reduced the inflammatory response in the present model suggesting its use as a suitable anesthetic agent for asthma.

A68. TISSUE REMODELING IN THE LUNG, 2012

RATIONALE: Volatile anesthetics play a protective role in experimental models of acute lung injur... more RATIONALE: Volatile anesthetics play a protective role in experimental models of acute lung injury. Isoflurane, halothane, and sevoflurane are volatile anesthetic agents routinely used in asthmatic patients; nevertheless, so far, there have been no studies examining their immunomodulatory effects in a chronically inflamed and remodeled airway, such as that found in asthma. We aimed to evaluate whether these volatile anesthetic agents reduce lung inflammation and remodeling, as well as improve lung morphofunction in experimental chronic allergic asthma. METHODS: Twenty-eight BALB/c mice (20-25 g) were sensitized and repeatedly challenged with ovalbumin. Twenty-four hours after the last challenge, animals were anesthetized with isoflurane (Iso), halothane (Halo), sevoflurane (Sevo) or control drug thiopental sodium (Thio). Lung static elastance (Est), resistive (DP1), and viscoelastic/inhomogeneous (DP2) pressures were computed by end-inflation occlusion method. Left lungs were fixed and stained for morphometrical analysis, while tumor necrosis factor (TNF)-alphaand transforming growth factor (TGF)-beta mRNA expressions were assessed in the right lung tissue using RT-PCR. RESULTS: Animals anesthetized with isoflurane, halothane, and sevoflurane presented lower DP1 (34%, 35%, and 49%), DP2 (45%, 48%, and 48%), Est (13%, 19%, and 22%) and alveolar collapse (25%, 48%, and 57%) compared to the Control group. Sevoflurane led to airway dilation (26%) associated with a greater reduction in the expressions of TNF-alpha and TGF-beta expressions compared to other groups. CONCLUSION: Of the three volatile anesthetic agents studied, sevoflurane was the most beneficial in the present model of chronic allergic asthma, lessening inflammatory and fibrogenic mediators while inducing airway dilation and reducing atelectasis.