Peripheral Blood Cell Mitochondrial DNA Integrity In A Rat Model Of Pseudomonas Aeruginosa-Induced Acute Lung Injury

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

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Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa

Shock ◽

10.1097/shk.0000000000000838 ◽

2017 ◽

Vol 48 (1) ◽

pp. 54-60 ◽

Cited By ~ 15

Author(s):

Yann-Leei Lee ◽

Boniface Obiako ◽

Olena M. Gorodnya ◽

Mykhaylo V. Ruchko ◽

Jamie L. Kuck ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Dna Damage ◽

Mitochondrial Dna ◽

Acute Lung Injury ◽

Lung Injury ◽

Organ System ◽

System Failure ◽

Mitochondrial Dna Damage ◽

Organ System Failure

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Regional lung hematocrit variation and assessment of acute lung injury

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.2.567 ◽

1994 ◽

Vol 77 (2) ◽

pp. 567-573 ◽

Cited By ~ 7

Author(s):

M. Kanazawa ◽

N. Hasegawa ◽

T. Urano ◽

K. Sayama ◽

S. Tasaka ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Blood Cell ◽

Coefficient Of Variation ◽

Peripheral Blood ◽

Guinea Pigs ◽

Blood Content ◽

Regional Lung ◽

Residual Blood ◽

Plasma Marker

Estimating blood content in the lung remains a key step in calculating lung water volume and microvascular permeability. We studied the effect of regional lung hematocrit (Hct) variation on assessment of acute lung injury. Escherichia coli endotoxin was administered in guinea pigs intravenously. Lung injury was evaluated by measuring the wet-to-dry weight ratio (W/D) and transvascular 125I-labeled albumin leakage for 3 h [tissue-to-plasma 125I-albumin ratio (T/P)] in five tissue samples from each animal. Residual blood content was corrected using either 51Cr-red blood cells as a blood cell marker, 99mTc-albumin as a plasma marker, or both, injected 10 min before the guinea pigs were killed. Lung Hct, estimated from the marker counts of lung and peripheral blood samples, was lower than peripheral blood Hct; intraindividual variation, represented by the standard deviation in each subject, was 0.024 +/- 0.015 for the control group (coefficient of variation 8.0 +/- 5.1%) and 0.026 +/- 0.013 for the endotoxin group (coefficient of variation 8.5 +/- 4.1%). Uncorrected W/D for residual blood content was greater than the corrected W/D. 99mTc-albumin correction gave values closer to the W/D corrected by both markers. T/P corrected by 99mTc-albumin showed smaller data variations than the values obtained with 51Cr-red blood cell correction, which was affected by variations in lung Hct. We recommend using a plasma marker to correct for blood content in assessing acute lung injury by W/D and T/P.

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Faculty Opinions recommendation of Peripheral Blood Cell-Stratified Subgroups of Inflamed Depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737303406.793577495 ◽

2020 ◽

Author(s):

Eric Hollander ◽

Genoveva Uzunova

Keyword(s):

Blood Cell ◽

Peripheral Blood ◽

Peripheral Blood Cell

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Plasma mitochondrial DNA levels are associated with acute lung injury and mortality in septic patients

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01437-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jia-yu Mao ◽

Dong-kai Li ◽

Hong-min Zhang ◽

Xiao-ting Wang ◽

Da-wei Liu

Keyword(s):

Mitochondrial Dna ◽

Acute Lung Injury ◽

Lung Injury ◽

Survival Rates ◽

Experimental Models ◽

College Hospital ◽

Medical College ◽

Incidence And Mortality ◽

Echocardiographic Parameters ◽

Post Hoc

Abstract Background Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. Methods We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined. Results Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38–6.64) vs 4.13 (3.20–5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608–8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647–6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection. Conclusions Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

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