Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury.

BACKGROUND: Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI. METHODS: Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin [IL-6], IL-12/12a, transforming growth factor-ß, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation. RESULTS: After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-ß showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups. CONCLUSIONS: Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI.

Sevoflurane attenuates systemic inflammation compared with propofol, but does not modulate neuro-inflammation: A laboratory rat study.

BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes. DESIGN: Laboratory rat study. SETTING: Basic research laboratories at the University Hospital Zurich and University Zurich Irchel between August 2014 and June 2016. PATIENTS: A total of 32 adult male Wistar rats. INTERVENTIONS: After tracheotomy and mechanical ventilation, the anaesthetised rats were monitored before sepsis was induced by using intravenous LPS or phosphate-buffered saline as control. Rats were sedated with propofol (10 mg kg h) or sevoflurane (2 vol%) continuously for 12 h. MAIN OUTCOME MEASURES: Systemic inflammatory markers such as cytokine-induced neutrophil chemo-attractant protein 1, monocyte chemo-tactic protein-1 and IL-6 were determined. The same cytokines were measured in brain tissue. Cellular response in the brain was assessed by defining neutrophil accumulation with myeloperoxidase and also activation of microglia with ionised calcium-binding adaptor molecule-1 and astrocytes with glial fibrillary acidic protein. Finally, brain injury was determined. RESULTS: Animals were haemodynamically stable in both sedation groups treated with LPS. Blood cytokine peak values were lower in the sevoflurane-LPS compared with propofol-LPS animals. In brain tissue of LPS animals, chemoattractant protein-1 was the only significantly increased cytokine (P = 0.003), however with no significance between propofol and sevoflurane. After LPS challenge, cerebral accumulation of neutrophils was observed. Microglia activation was pronounced in the hippocampus of animals treated with LPS (P = 0.006). LPS induced prominent astrogliosis (P < 0.001). There was no significant difference in microglia or astrocyte activation or apoptosis in the brain between sevoflurane and propofol. CONCLUSION: We have shown that systemic attenuation of inflammation by the volatile anaesthetic sevoflurane did not translate into attenuated neuro-inflammation in this LPS-induced inflammation model. TRIAL REGISTRATION: Animal approval No. 134/2014, Veterinäramt Zürich.

Characterization of carbon-coated magnetic nanoparticles using clinical blood coagulation assays: effect of PEG-functionalization and comparison to silica nanoparticles.

Intravascular application of magnetic nanocarriers is a critical step in the development of new therapeutic strategies, including magnetic drug targeting or hyperthermia. However, injection of particulate matter bears the intrinsic risk of contact activation of the blood coagulation cascade. In this work, we use point-of-care assays to study coagulation dynamics and clotting parameters in blood samples exposed to relevant concentrations of surface-functionalized carbon-coated iron carbide nanomagnets using unmodified nanomagnets and poly(ethylene)glycol-functionalized nanomagnets with different end-groups, including -OCH3, -NH2, -COOH, -IgG, and -ProteinA-protected-IgG (-IgG-ProtA). Silica nanoparticles with a comparable surface area are used as a reference material. For magnetic nanoparticles, we observe a decrease in clotting time by 25% compared to native blood at concentrations of 1 mg mL-1, independent of the surface functionalization, and only minor differences in receptor expression on platelets (GP-IIb-IIIa, CD62, and CD63) relative to control samples were observed. Interestingly, the inter-subject variance of the clotting time is similar to the nanoparticle-induced effect in a single subject with average clotting time. Whilst the present study is based on in vitro assays and a small group of healthy blood donors, the comparison to broadly used silica nanoparticles, and the fact that experimental intergroup variability is comparable to the observed effects from the carbon-coated nanomagnets suggests continuing investigations on their potential clinical use.