Early markers of ventilator-induced lung injury in rats

Rahim Behnia, Agostino Molteni, Christopher Waters, Ralph J. Panos, William F. Ward, H. William Schnaper, Chung Hsin Ts'ao

Research output: Contribution to journalArticle

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Abstract

Positive pressure ventilation with hyperdistention of the lungs (PPVHDL) causes microscopic lung injury in rats and in mice. This study compared lung lavage and serum levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine phosphokinase (CPK), lung lavage and plasma endothelin-1 (ET-1) concentration, lung tissue ET-1 mRNA expression, angiotensin converting enzyme (ACE) activity of lung homogenates, and histology of the lung structure in control and PPVHDL rats. Rats were anesthetized with pentobarbital. While control rats were breathing spontaneously, the PPVHDL rats were ventilated with a rodent ventilator delivering 30 percent oxygen, a tidal volume of 18.6 ± 4.5 ml/kg, and a respiratory rate of 55 to 60 per minute. End-tidal CO2 was maintained at 38- 40 mm Hg. After seven hours, rats were killed and the lungs were lavaged. Red blood cells were present in the sediment of lavage fluid in PPVHDL rats and their lung structure showed severe congestion, alveolar septa filled with red cells, and extravasation of red blood cells and inflammatory cells into the alveolar space. Lung lavage fluid AST and LDH were significantly higher in the PPVHDL compared with the control group (P < 0.03 and P < 0.061, respectively). Electrophoresis of the lung lavage LDH showed increased peak- 5 in the PPVHDL group. Serum LDH, CPK, AST, and potassium concentrations [K]+ were significantly higher in the PPVHDL rats whereas their serum total protein level was significantly lower than the control group (P < 0.001). Electrophoretic patterns of serum and lung lavage protein were similar in both groups indicating a transmural passage of serum protein from the intravascular to the intra-alveolar space. No significant difference was found in lung tissue ET-1 mRNA expression and lung protein concentration between the two groups. Lung ACE activity, in contrast, was significantly lower in PPVHDL rats. This study demonstrated that moderate alveolar hyperdistention caused significant structural lung damage accompanied by decreased ACE activity after seven hours of mechanical ventilation and that elevated lung lavage and serum LDH and AST levels in lung lavage and in serum might be early markers of ventilator-included lung injury in this rat model.

Original languageEnglish (US)
Pages (from-to)437-450
Number of pages14
JournalAnnals of Clinical and Laboratory Science
Volume26
Issue number5
StatePublished - Sep 18 1996

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Ventilator-Induced Lung Injury
Rats
Ventilation
Lung
Positive-Pressure Respiration
L-Lactate Dehydrogenase
Aspartate Aminotransferases
Bronchoalveolar Lavage
Enzyme activity
Endothelin-1
Peptidyl-Dipeptidase A
Cells
Creatinine
Blood
Phosphotransferases
Rat control
Tissue
Serum
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology
  • Molecular Biology
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology

Cite this

Behnia, R., Molteni, A., Waters, C., Panos, R. J., Ward, W. F., Schnaper, H. W., & Ts'ao, C. H. (1996). Early markers of ventilator-induced lung injury in rats. Annals of Clinical and Laboratory Science, 26(5), 437-450.

Early markers of ventilator-induced lung injury in rats. / Behnia, Rahim; Molteni, Agostino; Waters, Christopher; Panos, Ralph J.; Ward, William F.; Schnaper, H. William; Ts'ao, Chung Hsin.

In: Annals of Clinical and Laboratory Science, Vol. 26, No. 5, 18.09.1996, p. 437-450.

Research output: Contribution to journalArticle

Behnia, R, Molteni, A, Waters, C, Panos, RJ, Ward, WF, Schnaper, HW & Ts'ao, CH 1996, 'Early markers of ventilator-induced lung injury in rats', Annals of Clinical and Laboratory Science, vol. 26, no. 5, pp. 437-450.
Behnia R, Molteni A, Waters C, Panos RJ, Ward WF, Schnaper HW et al. Early markers of ventilator-induced lung injury in rats. Annals of Clinical and Laboratory Science. 1996 Sep 18;26(5):437-450.
Behnia, Rahim ; Molteni, Agostino ; Waters, Christopher ; Panos, Ralph J. ; Ward, William F. ; Schnaper, H. William ; Ts'ao, Chung Hsin. / Early markers of ventilator-induced lung injury in rats. In: Annals of Clinical and Laboratory Science. 1996 ; Vol. 26, No. 5. pp. 437-450.
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