Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation

Shawn D. Aaron, Franco Valenza, George Volgyesi, J. Brenden M Mullen, Arthur S. Slutsky, Thomas E. Stewart

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objectives: Increases in exhaled nitric oxide have been demonstrated to originate from the lungs of rats after septic lung injury. The aim of this study was to investigate whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) would prevent lipopolysaccharide (LPS)-induced increases in exhaled nitric oxide and whether this would have an effect on septic lung inflammation. Design: Prospective, randomized, placebo-controlled animal laboratory investigation. Setting: University laboratory Subjects: Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 27). Interventions: Rats were mechanically ventilated with air filtered to remove nitric oxide (espiratory rate 40 breaths/min, tidal volume 3 mL, positive end-expiratory pressure 0, FIO2 0.21). They were then randomize to receive intravenous infections of either L-NAME (25 mg/kg/hr x 4 hrs) (n = 11) or saline (n = 10). Both groups were again randomized to receive either LPS (Salmonella typhosa: 20 mg/kg iv x 1 dose) or an equal volume of saline 5 mins later. Thereafter, exhaled gas was collected in polyethylene bags for measurements of nitric oxide concentration. After 4 hrs, the rats wets killed and the lungs were preserved and examined histologically. To examine the effect of L- NAME and LPS on mesh arterial blood pressure, six additional rats underwent the same ventilation protocol with cannulation of the right interns; carotid artery so that systemic arterial pressures could be measured. Measurements and Main Results: Exhaled gas was collected and measurements of NO concentrations were made using chemiluminescence every 20 mins for 240 mins during ventilation. A total lung injury score was calculated by determining the extent of cellular infiltrate, exudate and hemorrhage. Mean arterial pressure was recorded every 5 mins for 20 mins and then at 20-min periods for 120 mins. Exhaled nitric oxide concentrations increased in all the LPS- treated rats that did not receive L-NAME by 120 mins; a plateau was reached by 190 mins that was ~4 times greater than control rats not treated with LPS (p

Original languageEnglish
Pages (from-to)309-314
Number of pages6
JournalCritical Care Medicine
Volume26
Issue number2
DOIs
Publication statusPublished - 1998

Fingerprint

Sepsis
Pneumonia
Nitric Oxide
NG-Nitroarginine Methyl Ester
Lipopolysaccharides
Arterial Pressure
Lung Injury
Ventilation
Gases
Salmonella typhi
Positive-Pressure Respiration
Tidal Volume
Laboratory Animals
Polyethylene
Exudates and Transudates
Pulmonary Edema
Luminescence
Carotid Arteries
Nitric Oxide Synthase
Catheterization

Keywords

  • Acute respiratory distress syndrome
  • Lipopolysaccharide
  • Nitric oxide
  • Pathology
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation. / Aaron, Shawn D.; Valenza, Franco; Volgyesi, George; Mullen, J. Brenden M; Slutsky, Arthur S.; Stewart, Thomas E.

In: Critical Care Medicine, Vol. 26, No. 2, 1998, p. 309-314.

Research output: Contribution to journalArticle

Aaron, Shawn D. ; Valenza, Franco ; Volgyesi, George ; Mullen, J. Brenden M ; Slutsky, Arthur S. ; Stewart, Thomas E. / Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation. In: Critical Care Medicine. 1998 ; Vol. 26, No. 2. pp. 309-314.
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