RESUMO
OBJECTIVE: Systemic PaO2 oscillations occur during cyclic recruitment and derecruitment of atelectasis in acute respiratory failure and might harm brain tissue integrity. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult anesthetized pigs. INTERVENTIONS: Pigs were randomized to a control group (anesthesia and extracorporeal circulation for 20 hr with constant PaO2, n = 10) or an oscillation group (anesthesia and extracorporeal circulation for 20 hr with artificial PaO2 oscillations [3 cycles min⻹], n = 10). Five additional animals served as native group (n = 5). MEASUREMENTS AND MAIN RESULTS: Outcome following exposure to artificial PaO2 oscillations compared with constant PaO2 levels was measured using 1) immunohistochemistry, 2) real-time polymerase chain reaction for inflammatory markers, 3) receptor autoradiography, and 4) transcriptome analysis in the hippocampus. Our study shows that PaO2 oscillations are transmitted to brain tissue as detected by novel ultrarapid oxygen sensing technology. PaO2 oscillations cause significant decrease in NISSL-stained neurons (p < 0.05) and induce inflammation (p < 0.05) in the hippocampus and a shift of the balance of hippocampal neurotransmitter receptor densities toward inhibition (p < 0.05). A pathway analysis suggests that cerebral immune and acute-phase response may play a role in mediating PaO2 oscillation-induced brain injury. CONCLUSIONS: Artificial PaO2 oscillations cause mild brain injury mediated by inflammatory pathways. Although artificial PaO2 oscillations and endogenous PaO2 oscillations in lung-diseased patients have different origins, it is likely that they share the same noxious effect on the brain. Therefore, PaO2 oscillations might represent a newly detected pathway potentially contributing to the crosstalk between acute lung and remote brain injury.
Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/fisiopatologia , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Animais , Gasometria , Oxigenação por Membrana Extracorpórea/métodos , Mediadores da Inflamação/metabolismo , Atelectasia Pulmonar/prevenção & controle , RNA Complementar/metabolismo , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Oxidative stress due to free radical formation is an important mechanism of secondary brain damage following traumatic brain injury (TBI). Phenothiazine has been found to be a strong antioxidant in eukaryotic cells in vitro and in invertebrates in vivo. The present study was designed to determine the neuroprotective potency of unsubstituted phenothiazine in a paradigm of acute brain injury. Thirty minutes after pneumatic, controlled cortical impact (CCI) injury, C57BI6 mice were randomly assigned to "low dose" (3 mg/kg, LD) or "high dose" (30 mg/kg, HD) s.c. phenothiazine or vehicle treatment. Brain lesion, neurofunctional impairment, body weight, and markers of cerebral inflammation were determined 24h after the insult. Phenothiazine treatment dose-dependently reduced brain lesion volume (LD: -19.8%; HD: -26.1%) and posttraumatic body weight loss. There were no significant differences in the neurological function score and in markers of cerebral inflammation (Iba-1 positive cells, TNFα expression), whereas iNOS expression was significantly lower compared to vehicle-treated animals. Phenothiazine appears to modify in a post-treatment protocol certain aspects of secondary brain damage in vivo at unusually low concentrations, in particular the cortical contusion volume after TBI. The potential role of the reduced iNOS expression is unclear at present.
Assuntos
Antioxidantes/farmacologia , Lesões Encefálicas/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Fenotiazinas/farmacologia , Animais , Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Contagem de Células , Relação Dose-Resposta a Droga , Expressão Gênica , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Fenotiazinas/uso terapêutico , Distribuição AleatóriaRESUMO
BACKGROUND: Autologous blood transfusion (ABT), for example, by means of cell saver equipment, is used to reduce the need for allogenic blood transfusion in patients with high perioperative blood loss. This study investigated the effect of blood/extracorporal surface interaction during withdrawal and retransfusion of shed autologous blood on cerebral inflammation in rats. Rats subjected to hypotension with cerebral ischemia served as positive controls. METHODS: Eighty-eight male Sprague-Dawley rats were anesthetized with sevoflurane, instrumented, and randomly assigned to the following groups: sham-operation (SHAM), autologous blood withdrawal/transfusion only (ABT), or bilateral carotid artery occlusion and autologous blood withdrawal/transfusion (BCAO/ABT). Inflammatory gene expression was investigated with real-time RT-polymerase chain reaction at 6, 12, and 24 hours after SHAM, ABT, or BCAO/ABT in brain hippocampal tissue. Naive rats were investigated as reference. RESULTS: ABT alone had no impact on hippocampal inflammatory gene expression, whereas after BCAO/ABT tumor necrosis factor-alpha (10.7 fold at 24 h), interleukin-1ß (2.1 fold at 6 h), interleukin-6 (35.7 fold at 24 h), COX-2 (9.3 fold at 6 h), and inducible nitric oxide synthase (3.4 fold at 24 h) increased compared with SHAM. CONCLUSIONS: ABT by itself did not provoke an inflammatory reaction in the healthy brain. However, in combination with cerebral ischemia the induction of a broad spectrum of inflammatory parameters indicates an inflammatory reaction of the hippocampus beginning after 6 hours and being most pronounced after 24 hours. Therefore, this study shows that cerebral inflammation is not induced by ABT after contact with extracorporal surfaces in rats.