Effect of low-level laser therapy on the inflammatory response in an experimental model of ventilator-induced lung injury.

The effect of low-level laser therapy (LLLT) on an experimental model of ventilator-induced lung injury (VILI) was evaluated in this study. 24 adult Wistar rats were randomized into four groups: protective mechanical ventilation (PMV), PMV + laser, VILI and VILI + laser. The animals of the PMV and VILI groups were ventilated with tidal volumes of 6 and 35 ml kg-1, respectively, for 90 minutes. After the first 60 minutes of ventilation, the animals in the laser groups were irradiated (808 nm, 100 mW power density, 20 J cm-2 energy density, continuous emission mode, and exposure time of 5 s) and after 30 minutes of irradiation, the animals were euthanized. Lung samples were removed for morphological analysis, bronchoalveolar lavage (BAL) and real time quantitative polynucleotide chain reaction (RT-qPCR). The VILI group showed a greater acute lung injury (ALI) score with an increase in neutrophil infiltration, higher neutrophil count in the BAL fluid and greater cytokine mRNA expression compared to the PMV groups (p < 0.05). The VILI + laser group when compared to the VILI group showed a lower ALI score (0.35 ± 0.08 vs. 0.54 ± 0.13, p < 0.05), alveolar neutrophil infiltration (7.00 ± 5.73 vs. 21.50 ± 9.52, p < 0.05), total cell count (1.90 ± 0.71 vs. 4.09 ± 0.96 × 105, p < 0.05) and neutrophil count in the BAL fluid (0.60 ± 0.37 vs. 2.28 ± 0.48 × 105, p < 0.05). Moreover, LLLT induced a decrease in pro-inflammatory and an increase of anti-inflammatory mRNA levels compared to the VILI group (p < 0.05). In conclusion, LLLT was found to reduce the inflammatory response in an experimental model of VILI.

Emphysema induced by elastase alters the mRNA relative levels from DNA repair genes in acute lung injury in response to sepsis induced by lipopolysaccharide administration in Wistar rats.

Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. MATERIALS AND METHODS: Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. RESULTS: Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. CONCLUSION: Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.

Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS.

Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation.

Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ∼50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1(S). Higher-molecular-weight LANA1(S) isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1(S) isoforms initiate downstream within the central repeat 1 domain. LANA1(S) proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.

Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase.

Host colonisation by lymphotropic gammaherpesviruses depends critically on the expansion of viral genomes in germinal centre (GC) B cells. Yet, host and virus molecular mechanisms involved in driving such proliferation remain largely unknown. Here, we show that the ORF73 protein encoded by the murid herpesvirus-4 (MuHV-4) inhibits host nuclear factor-kappa B (NF-kappaB) transcriptional activity through poly-ubiquitination and subsequent proteasomal-dependent nuclear degradation of the NF-kappaB family member p65/RelA. The mechanism involves the assembly of an ElonginC/Cullin5/SOCS (suppressors of cytokine signalling)-like complex, mediated by an unconventional viral SOCS-box motif present in ORF73. Functional deletion of this SOCS-box motif ablated NF-kappaB inhibitory effect of ORF73, suppressed MuHV-4 expansion in GC B cells and prevented MuHV-4 persistent infection in mice. These findings demonstrate that viral inhibition of NF-kappaB activity in latently infected GC centroblasts is critical for the establishment of a gammaherpesvirus persistent infection, underscoring the physiological importance of proteasomal degradation of RelA/NF-kappaB as a regulatory mechanism of this signalling pathway.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide.

OBJECTIVE: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. METHODS: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. RESULTS: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. CONCLUSION: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

Protective mechanical ventilation in patients with risk factors for ARDS: prospective cohort study.

OBJECTIVE: To evaluate the association that protective mechanical ventilation (MV), based on VT and maximum distending pressure (MDP), has with mortality in patients at risk for ARDS. METHODS: This was a prospective cohort study conducted in an ICU and including 116 patients on MV who had at least one risk factor for the development of ARDS. Ventilatory parameters were collected twice a day for seven days, and patients were divided into two groups (protective MV and nonprotective MV) based on the MDP (difference between maximum airway pressure and PEEP) or VT. The outcome measures were 28-day mortality, ICU mortality, and in-hospital mortality. The risk factors associated with the adoption of nonprotective MV were also assessed. RESULTS: Nonprotective MV based on VT and MDP was applied in 49 (42.2%) and 38 (32.8%) of the patients, respectively. Multivariate Cox regression showed that protective MV based on MDP was associated with lower in-hospital mortality (hazard ratio = 0.37; 95% CI: 0.19-0.73) and lower ICU mortality (hazard ratio = 0.40; 95% CI: 0.19-0.85), after adjustment for age, Simplified Acute Physiology Score 3, and vasopressor use, as well as the baseline values for PaO2/FiO2 ratio, PEEP, pH, and PaCO2. These associations were not observed when nonprotective MV was based on the VT. CONCLUSIONS: The MDP seems to be a useful tool, better than VT, for adjusting MV in patients at risk for ARDS.

Impact of Early Passive Exercise With Cycle Ergometer on Ventilator Interaction.

BACKGROUND: Early exercise has been recommended in critically ill patients, but its impact on subject-ventilator interaction is still unclear. Therefore, the aim of this study was to evaluate the occurrence of subject-ventilator asynchrony during passive exercise in mechanically ventilated subjects. METHODS: This study included deeply sedated subjects who were under mechanical ventilation for < 72 h. Subjects were coupled to a cycle ergometer and maintained at rest for 5 min (baseline period). After this period, they started 20 min of passive exercise, followed by 10 min of rest (recovery period). The occurrence of asynchrony was monitored by the analysis of flow and airway pressure waveforms, registered throughout the protocol during the baseline, exercise, and recovery periods. Hemodynamic and respiratory parameters were registered at the end of each period. Finally, arterial blood gas analysis was performed twice, at the end of the baseline period and at the end of the recovery period. RESULTS: 8 subjects were enrolled (63.3 ± 16.7 y old, 50% male). The asynchrony index increased during exercise (median 32.1% [interquartile range (IQR) 18.6-47.6%]), compared to baseline (median 6.6% [IQR 3.9-10.4%]), returning to initial levels during the recovery period (median 2.7% [IQR 0-12.2%]). The most frequent types of asynchrony were ineffective triggering (index of 11.8% [IQR 1.2-22.5%] during exercise, compared to 2.0% [IQR 1.4-4.4%] at baseline), and insufficient flow (index of 11.7% [IQR 4.7-19.3%] during exercise, compared to 2.0% [IQR 1.1 to 3.3%] at baseline). There were no significant changes in the hemodynamic and respiratory variables. CONCLUSIONS: Early cycle ergometer passive exercise in deeply sedated subjects can worsen subject-ventilator interaction, due to ineffective triggering and insufficient flow. Adjustments in the ventilatory parameters may be necessary to avoid asynchrony during exercise.

Acute Lung Injury in Response to Intratracheal Instillation of Lipopolysaccharide in an Animal Model of Emphysema Induced by Elastase.

The response of lungs with emphysema to an acute lung injury (ALI) remains unclear. This study compared the lung response to intratracheal instillation of lipopolysaccharide (LPS) in rats with and without emphysema. Twenty-four Wistar rats were randomized to four groups: control group (C-G), ALI group (ALI-G), emphysema group (E-G), emphysema and ALI group (E-ALI-G). Euthanasia and the following analysis were performed 24 h after ALI induction: lung histology, bronchoalveolar lavage (BAL), mRNA expression of inflammatory mediators, and blood gas measures. The histological analysis showed that animals of ALI-G (0.55 ± 0.15) and E-ALI-G (0.69 ± 0.08) had a higher ALI score compared to C-G (0.12 ± 0.04) and E-G (0.16 ± 0.04) (p < 0.05). The analysis of each component of the score demonstrated that ALI-G and E-ALI-G had greater alveolar and interstitial neutrophil infiltration, as well as greater amount of alveolar proteinaceous debris. Comparing the two groups that received LPS, there was a trend of higher ALI in the E-ALI-G, specially due to a higher neutrophil infiltration in the alveolar spaces and a higher septal thickening. Total cell count (E-G = 3.09 ± 0.83; ALI-G = 4.45 ± 1.9; E-ALI-G = 5.9 ± 2.1; C-G = 0.73 ± 0.37 × 105) and neutrophil count (E-G = 0.69 ± 0.35; ALI-G = 2.53 ± 1.09; E-ALI-G = 3.86 ± 1.4; C-G = 0.09 ± 0.07 × 105) in the BAL were higher in the groups E-G, ALI-G, and E-ALI-G when compared to C-G (p < 0.05). The IL-6, TNF-α, and CXCL2 mRNA expressions were higher in the animals that received LPS (ALI-G and E-ALI-G) compared to the C-G and E-G (p < 0.05). No statistically significant difference was observed in the BAL cellularity and in the expression of inflammatory mediators between the ALI-G and the E-ALI-G. The severity of ALI in response to intratracheal instillation of LPS did not show difference in rats with and without intratracheal-induced emphysema.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide / Efeitos das áreas atelectásicas no tecido pulmonar circundante durante a ventilação mecânica em um modelo experimental de lesão pulmonar aguda induzida por lipopolissacarídeo

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

Protective mechanical ventilation in patients with risk factors for ARDS: prospective cohort study / Ventilação mecânica protetora em pacientes com fator de risco para SDRA: estudo de coorte prospectiva

ABSTRACT Objective: To evaluate the association that protective mechanical ventilation (MV), based on VT and maximum distending pressure (MDP), has with mortality in patients at risk for ARDS. Methods: This was a prospective cohort study conducted in an ICU and including 116 patients on MV who had at least one risk factor for the development of ARDS. Ventilatory parameters were collected twice a day for seven days, and patients were divided into two groups (protective MV and nonprotective MV) based on the MDP (difference between maximum airway pressure and PEEP) or VT. The outcome measures were 28-day mortality, ICU mortality, and in-hospital mortality. The risk factors associated with the adoption of nonprotective MV were also assessed. Results: Nonprotective MV based on VT and MDP was applied in 49 (42.2%) and 38 (32.8%) of the patients, respectively. Multivariate Cox regression showed that protective MV based on MDP was associated with lower in-hospital mortality (hazard ratio = 0.37; 95% CI: 0.19-0.73) and lower ICU mortality (hazard ratio = 0.40; 95% CI: 0.19-0.85), after adjustment for age, Simplified Acute Physiology Score 3, and vasopressor use, as well as the baseline values for PaO2/FiO2 ratio, PEEP, pH, and PaCO2. These associations were not observed when nonprotective MV was based on the VT. Conclusions: The MDP seems to be a useful tool, better than VT, for adjusting MV in patients at risk for ARDS.

RESUMO Objetivo: Avaliar a associação da ventilação mecânica (VM) protetora, com base no VT e na pressão de distensão máxima (PDM), com a mortalidade em pacientes com fator de risco para SDRA. Métodos: Este estudo de coorte prospectivo foi conduzido em uma UTI e incluiu 116 pacientes em VM que apresentavam pelo menos um fator de risco para o desenvolvimento de SDRA. Os parâmetros ventilatórios foram coletados duas vezes ao dia durante sete dias, e os pacientes foram divididos em dois grupos (VM protetora e VM não protetora) com base na PDM (diferença entre pressão máxima de vias aéreas e PEEP) ou no VT. Os desfechos foram mortalidade em 28 dias, mortalidade na UTI e mortalidade hospitalar. Os fatores de risco associados com a adoção da VM não protetora também foram avaliados. Resultados: A VM não protetora com base no VT e na PDM ocorreu em 49 (42,2%) e em 38 (32,8%) dos pacientes, respectivamente. A regressão multivariada de Cox mostrou que a VM protetora com base na PDM associou-se a menor mortalidade hospitalar (hazard ratio = 0,37; IC95%: 0,19-0,73) e em UTI (hazard ratio = 0,40; IC95%, 0,19-0,85), após ajuste para idade, Simplified Acute Physiology Score 3, uso de vasopressor e valores basais de PaO2/FiO2, PEEP, pH e PaCO2. Essas associações não foram observadas quando a VM não protetora foi baseada no VT. Conclusões: A PDM parece ser uma ferramenta útil, melhor do que o VT, para o ajuste da VM em pacientes sob risco para SDRA.

Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury.

OBJECTIVE: To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. METHODS: Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. RESULTS: At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. CONCLUSIONS: Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated. OBJETIVO: Avaliar os efeitos da administração de dexametasona antes da indução de lesão pulmonar induzida por ventilação mecânica (LPIVM) na evolução temporal dessa lesão. MÉTODOS: Ratos Wistar foram alocados em um dos três grupos: administração de dexametasona pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. RESULTADOS: Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p < 0,05). A administração de dexametasona antes da LPIVM reduziu a gravidade da lesão pulmonar. Em 4 e 24 h após a indução, o escore de LPA no grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p < 0,05). As contagens de neutrófilos no lavado broncoalveolar estavam aumentadas nos grupos controle e dexametasona, com pico em 4 h após LPIVM (p < 0,05). Entretanto, as contagens de neutrófilos foram menores no grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p < 0,05). O pré-tratamento com dexametasona também impediu o comprometimento da oxigenação após a indução visto no grupo controle. CONCLUSÕES: A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.

Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury / Pré-tratamento com dexametasona atenua a lesão pulmonar induzida por ventilação mecânica em modelo experimental

ABSTRACT Objective: To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Methods: Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. Results: At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. Conclusions: Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated.

RESUMO Objetivo: Avaliar os efeitos da administração de dexametasona antes da indução de lesão pulmonar induzida por ventilação mecânica (LPIVM) na evolução temporal dessa lesão. Métodos: Ratos Wistar foram alocados em um dos três grupos: administração de dexametasona pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. Resultados: Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p < 0,05). A administração de dexametasona antes da LPIVM reduziu a gravidade da lesão pulmonar. Em 4 e 24 h após a indução, o escore de LPA no grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p < 0,05). As contagens de neutrófilos no lavado broncoalveolar estavam aumentadas nos grupos controle e dexametasona, com pico em 4 h após LPIVM (p < 0,05). Entretanto, as contagens de neutrófilos foram menores no grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p < 0,05). O pré-tratamento com dexametasona também impediu o comprometimento da oxigenação após a indução visto no grupo controle. Conclusões: A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.