BackgroundThe renin-angiotensin system (RAS) plays a role in the pathogenesis of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang-II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce injury, inflammation and fibrosis in an experimental model of ARDS in the acute and late phases.MethodsMale Sprague Dawley rats underwent an instillation of 0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute ARDS study, acid-injured rats were subjected to high stretch mechanical ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion of either vehicle (saline), Ang-(1-7) at low dose(0.27 μg/kg/h) (ALD), or high dose (60 μg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards. Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to assess the injury. For the late ARDS study, after HCl instillation rats were randomized to either vehicle or high dose Ang-(1-7) (300 μg/kg/day) infused by mini osmotic pumps for two weeks, and lung hydroxyproline content measured.ResultsIn the acute ARDS study, Ang-(1-7) led to a significant improvement in oxygenation (PaO2/FiO2 : vehicle 359 ± 86; ALD 436 ± 72; AHD 44 442 ± 56; ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 ± 2,234; ALD 2,496 ± 621; AHD 2,744 ± 119/mm3; ANOVA p = 0.004). Only treatment with high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 ± 34; AHD 96 ± 34/ μl; p = 0.033). Interestingly also delayed administration of Ang-(1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased hydroxyproline content (649 ± 202 and 1,117 ± 297 μg/lung; p < 0.05).ConclusionsAngiotensin-(1-7), decreased the severity of acute lung injury and inflammation induced by combined acid aspiration and high stretch ventilation. Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks following acid aspiration injury. These results call for further research on Ang-(1-7) as possible therapy for ARDS.
BackgroundBiofilm accumulates within the endotracheal tube (ETT) early after intubation. Contaminated secretions in the ETT are associated with increased risk for microbial dissemination in the distal airways and increased resistance to airflow. We evaluated the effectiveness of micro computed tomography (MicroCT) for the quantification of ETT inner volume reduction in critically ill patients.MethodsWe injected a known amount of gel into unused ETT to simulate secretions. We calculated the volume of gel analyzing MicroCT scans for a length of 20 cm. We then collected eleven ETTs after extubation of critically ill patients, recording clinical and demographical data. We assessed the amount of secretions by MicroCT and obtained ETT microbiological cultures.ResultsGel volumes assessed by MicroCT strongly correlated with injected gel volumes (p < 0.001, r2 = 0.999).MicroCT revealed the accumulation of secretions on all the ETTs (median 0.154, IQR:0.02-0.837 mL), corresponding to an average cross-sectional area reduction of 1.7%. The amount of secretions inversely correlated with patients’ age (p = 0.011, rho = −0.727) but not with days of intubation, SAPS2, PaO2/FiO2 assessed on admission. Accumulation of secretions was higher in the cuff region (p = 0.003). Microbial growth occurred in cultures from 9/11 ETTs, and did not correlate with secretions amount. In 7/11 cases the same microbes were identified also in tracheal aspirates.ConclusionsMicroCT appears as a feasible and precise technique to measure volume of secretions within ETTs after extubation. In patients, secretions tend to accumulate in the cuff region, with high variability among patients.
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