Mechanical ventilation affects the microecology of the rat respiratory tract

Background: The most common 'second strike' in mechanically ventilated patients is a pulmonary infection caused by the ease with which bacteria can invade and colonize the lungs due to mechanical ventilation. At the same time, metastasis of lower airway microbiota may have significant implications in the development of intubation mechanical ventilation lung inflammation. Thus, we establish a rat model of tracheal intubation with mechanical ventilation and explore the effects of mechanical ventilation on lung injury and microbiological changes in rats. Methods: Sprague-Dawley rats were randomized into control, Spontaneously Breathing (1, 3, 6 hours), Mechanical ventilation(1, 3, 6 hours) groups. Lung wet to dry weight ratio (W/D weight ratio) and Lung histopathological injury score were evaluated.16SrDNA sequencing was performed to explore respiratory flora changes. Results: Bacterial diversity was comparable between healthy and intubation mechanical ventilation rats, with time relation. Ordination analyses revealed that samples clustered more dispersing by tracheal intubation and mechanical ventilation. Finally, predicted metagenomes suggested a substantial increase in biofilm formation phenotype during early tracheal intubation and mechanical ventilation. Conclusion: Collectively, these results establish a link between the duration of mechanical ventilation and alterations to the respiratory tract microecology. In future studies, we hope to discover the effectiveness of new immunomodulatory or probiotic bacteria to prevent airway diseases associated with ventilator therapy.

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Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

Mediators of Inflammation ◽

10.1155/2018/8352727 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Xiaozhu Zhai ◽

Zhengfei Yang ◽

Guanghui Zheng ◽

Tao Yu ◽

Peng Wang ◽

...

Keyword(s):

Troponin I ◽

Cecal Ligation ◽

Weight Ratio ◽

High Mobility ◽

Dry Weight ◽

Cecal Ligation And Puncture ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Potential Biomarker ◽

Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

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Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽

10.1161/hyp.36.suppl_1.723-a ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 723-723

Author(s):

Qing-Feng Tao ◽

Diego Martinez vasquez ◽

Ricardo Rocha ◽

Gordon H Williams ◽

Gail K Adler

Keyword(s):

Myocardial Infarction ◽

Drinking Water ◽

Mineralocorticoid Receptor ◽

Critical Role ◽

Weight Ratio ◽

Myocardial Necrosis ◽

Receptor Activation ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

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Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽

10.1161/hyp.66.suppl_1.114 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Luciana C Veiras ◽

Jiyang Han ◽

Donna L Ralph ◽

Alicia A McDonough

Keyword(s):

Blood Pressure ◽

Urine Volume ◽

Weight Ratio ◽

Distal Tubule ◽

Reduce Blood Pressure ◽

Ang Ii ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

K Secretion ◽

Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

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Study of the Variability in Upper and Lower Airway Morphology in Sprague-Dawley Rats Using Modern Micro-CT Scan-Based Segmentation Techniques

The Anatomical Record ◽

10.1002/ar.20877 ◽

2009 ◽

Vol 292 (5) ◽

pp. 720-727 ◽

Cited By ~ 12

Author(s):

Jan W. De Backer ◽

Wim G. Vos ◽

Patricia Burnell ◽

Stijn L. Verhulst ◽

Phil Salmon ◽

...

Keyword(s):

Ct Scan ◽

Lower Airway ◽

Micro Ct ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Airway Morphology

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Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats

AJP Renal Physiology ◽

10.1152/ajprenal.00300.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. F1490-F1500 ◽

Cited By ~ 73

Author(s):

Markus Schafflhuber ◽

Nicola Volpi ◽

Anke Dahlmann ◽

Karl F. Hilgers ◽

Francesca Maccari ◽

...

Keyword(s):

Binding Capacity ◽

Dry Weight ◽

Sprague Dawley ◽

Dietary Salt ◽

Salt Restriction ◽

Sprague Dawley Rats ◽

Low Salt ◽

Total Body ◽

Dietary Salt Restriction

The idea that an osmotically inactive Na+ storage pool exists that can be varied to accommodate states of Na+ retention and/or Na+ loss is controversial. We speculated that considerable amounts of osmotically inactive Na+ are lost with growth and that additional dietary salt excess or salt deficit alters the polyanionic character of extracellular glycosaminoglycans in osmotically inactive Na+ reservoirs. Six-week-old Sprague-Dawley rats were fed low-salt (0.1%; LS) or high-salt (8%; HS) diets for 1 or 4 wk. At their death, we separated the tissues and determined their Na+, K+, and water content. Three weeks of growth reduced the total body Na+ content relative to dry weight (rTBNa+) by 23%. This “growth-programmed” Na+ loss originated from the bone and the completely skinned and bone-removed carcasses. The Na+ loss was osmotically inactive (45–50%) or osmotically active (50–55%). In rats aged 10 wk, compared with HS, 4 wk of LS reduced rTBNa+ by 9%. This dietary-induced Na+ loss was osmotically inactive (≈50%) and originated largely from the skin, while ≈50% was osmotically active. LS for 1 wk did not reduce skin Na+ content. The mobilization of osmotically inactive skin Na+ with long-term salt deprivation was associated with decreased negatively charged skin glycosaminoglycan content and thereby a decreased water-free Na+ binding capacity in the extracellular matrix. Our data not only serve to explain discrepant results in salt balance studies but also show that glycosaminoglycans may provide an actively regulated interstitial cation exchange mechanism that participates in volume and blood pressure homeostasis.

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Respiratory tract toxicity of inhaled hydrogen sulfide in Fischer-344 rats, Sprague–Dawley rats, and B6C3F1 mice following subchronic (90-day) exposure

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2004.03.010 ◽

2004 ◽

Vol 198 (1) ◽

pp. 29-39 ◽

Cited By ~ 26

Author(s):

David C Dorman ◽

Melanie F Struve ◽

Elizabeth A Gross ◽

Karrie A Brenneman

Keyword(s):

Hydrogen Sulfide ◽

Respiratory Tract ◽

Fischer 344 Rats ◽

Sprague Dawley ◽

Fischer 344 ◽

Sprague Dawley Rats ◽

B6c3f1 Mice

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Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction

Journal of Applied Physiology ◽

10.1152/japplphysiol.91106.2008 ◽

2009 ◽

Vol 106 (2) ◽

pp. 385-394 ◽

Cited By ~ 67

Author(s):

Melissa A. Whidden ◽

Joseph M. McClung ◽

Darin J. Falk ◽

Matthew B. Hudson ◽

Ashley J. Smuder ◽

...

Keyword(s):

Oxidative Stress ◽

Mechanical Ventilation ◽

Xanthine Oxidase ◽

Prolonged Mechanical Ventilation ◽

Oxidative Injury ◽

Contractile Dysfunction ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Oxidant Production ◽

Diaphragmatic Weakness

Respiratory muscle weakness resulting from both diaphragmatic contractile dysfunction and atrophy has been hypothesized to contribute to the weaning difficulties associated with prolonged mechanical ventilation (MV). While it is clear that oxidative injury contributes to MV-induced diaphragmatic weakness, the source(s) of oxidants in the diaphragm during MV remain unknown. These experiments tested the hypothesis that xanthine oxidase (XO) contributes to MV-induced oxidant production in the rat diaphragm and that oxypurinol, a XO inhibitor, would attenuate MV-induced diaphragmatic oxidative stress, contractile dysfunction, and atrophy. Adult female Sprague-Dawley rats were randomly assigned to one of six experimental groups: 1) control, 2) control with oxypurinol, 3) 12 h of MV, 4) 12 h of MV with oxypurinol, 5) 18 h of MV, or 6) 18 h of MV with oxypurinol. XO activity was significantly elevated in the diaphragm after MV, and oxypurinol administration inhibited this activity and provided protection against MV-induced oxidative stress and contractile dysfunction. Specifically, oxypurinol treatment partially attenuated both protein oxidation and lipid peroxidation in the diaphragm during MV. Further, XO inhibition retarded MV-induced diaphragmatic contractile dysfunction at stimulation frequencies >60 Hz. Collectively, these results suggest that oxidant production by XO contributes to MV-induced oxidative injury and contractile dysfunction in the diaphragm. Nonetheless, the failure of XO inhibition to completely prevent MV-induced diaphragmatic oxidative damage suggests that other sources of oxidant production are active in the diaphragm during prolonged MV.

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