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 language | English |
|---|---|
| Pages (from-to) | 309-314 |
| Number of pages | 6 |
| Journal | Critical Care Medicine |
| Volume | 26 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1998 |
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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 journal › Article
}
TY - JOUR
T1 - Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation
AU - Aaron, Shawn D.
AU - Valenza, Franco
AU - Volgyesi, George
AU - Mullen, J. Brenden M
AU - Slutsky, Arthur S.
AU - Stewart, Thomas E.
PY - 1998
Y1 - 1998
N2 - 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
AB - 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
KW - Acute respiratory distress syndrome
KW - Lipopolysaccharide
KW - Nitric oxide
KW - Pathology
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=0031941645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031941645&partnerID=8YFLogxK
U2 - 10.1097/00003246-199802000-00033
DO - 10.1097/00003246-199802000-00033
M3 - Article
VL - 26
SP - 309
EP - 314
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 2
ER -