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1.
BMC Neurosci ; 22(1): 31, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926378

RESUMO

BACKGROUND: Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg-1 and nine animals were ventilated with a tidal volume of 10 mL × kg-1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg-1 × h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. RESULTS: No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation. CONCLUSIONS: Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.


Assuntos
Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Pulmão/fisiologia , Respiração Artificial/métodos , Sepse/metabolismo , Volume de Ventilação Pulmonar/fisiologia , Animais , Lesões Encefálicas/terapia , Circulação Cerebrovascular/fisiologia , Masculino , Sepse/terapia , Suínos
2.
BMC Pulm Med ; 20(1): 206, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736620

RESUMO

BACKGROUND: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. METHOD: One group of anaesthetised, domestic-breed, 9-12 weeks old, pigs were ventilated with protective ventilation (VT 6 mL x kg- 1, PEEP 10 cmH2O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (VT 10 mL x kg- 1, PEEP 5 cm H2O) n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 µg x kg- 1 x h- 1 for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. RESULTS: The protective ventilation group had lower levels of cf-DNA in arterial (p = 0.02) and hepatic venous blood (p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. CONCLUSIONS: Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation.


Assuntos
Ácidos Nucleicos Livres/sangue , Complicações Pós-Operatórias/sangue , Respiração Artificial , Sepse/sangue , Animais , Ácidos Nucleicos Livres/análise , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Veias Hepáticas , Inflamação , Masculino , Pico do Fluxo Expiratório , Veia Porta , Suínos , Volume de Ventilação Pulmonar
3.
PLoS One ; 15(10): e0240753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33108383

RESUMO

BACKGROUND: Immune system suppression during critical care contributes to the risk of acquired bacterial infections with Pseudomonas (P.) aeruginosa. Repeated exposure to endotoxin can attenuate systemic inflammatory cytokine responses. Mechanical ventilation affects the systemic inflammatory response to various stimuli. AIM: To study the effect of pre-exposure to mechanical ventilation with and without endotoxin-induced systemic inflammation on P. aeruginosa growth and wet-to-dry weight measurements on lung tissue and plasma and bronchoalveolar lavage levels of tumor necrosis factor alpha, interleukins 6 and 10. METHODS: Two groups of pigs were exposed to mechanical ventilation for 24 hours before bacterial inoculation and six h of experimental pneumonia (total experimental time 30 h): A30h+Etx (n = 6, endotoxin 0.063 µg x kg-1 x h-1) and B30h (n = 6, saline). A third group, C6h (n = 8), started the experiment at the bacterial inoculation unexposed to endotoxin or mechanical ventilation (total experimental time 6 h). Bacterial inoculation was performed by tracheal instillation of 1x1011 colony-forming units of P. aeruginosa. Bacterial cultures and wet-to-dry weight ratio analyses were done on lung tissue samples postmortem. Separate group comparisons were done between A30h+Etx vs.B30h (Inflammation) and B30h vs. C6h (Ventilation Time) during the bacterial phase of 6 h. RESULTS: P. aeruginosa growth was highest in A30h+Etx, and lowest in C6h (Inflammation and Ventilation Time both p<0.05). Lung wet-to-dry weight ratios were highest in A30h+Etx and lowest in B30h (Inflammation p<0.01, Ventilation Time p<0.05). C6h had the highest TNF-α levels in plasma (Ventilation Time p<0.01). No differences in bronchoalveolar lavage variables between the groups were observed. CONCLUSIONS: Mechanical ventilation and systemic inflammation before the onset of pneumonia increase the growth of P. aeruginosa in lung tissue. The attenuated growth of P. aeruginosa in the non-pre-exposed animals (C6h) was associated with a higher systemic TNF-α production elicited from the bacterial challenge.


Assuntos
Endotoxemia/complicações , Pulmão/microbiologia , Pneumonia/complicações , Pneumonia/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Respiração Artificial , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Inflamação/urina , Masculino , Nitritos/urina , Norepinefrina/metabolismo , Tamanho do Órgão , Perfusão , Suínos
4.
Intensive Care Med Exp ; 5(1): 40, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28861863

RESUMO

BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01). CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

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