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Pretreatment with N-nitro-L-arginine methyl ester improved oxygenation after inhalation of nitric oxide in newborn piglets with Escherichia coli pneumonia and sepsis.

Chang YS, Kang S, Ko SY, Park WS - J. Korean Med. Sci. (2006)

Bottom Line: E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI.Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection.This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, 50 Ilwon-Dong, Gangnam-Gu, Seoul, Korea.

ABSTRACT
We evaluated the effects of a combined therapy of pre-blockade endogenous nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn piglets were randomized into 5 groups: control, E. coli pneumonia control, pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI. Only two of 8 animals with L-NAME pretreated pneumonia survived. Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection. This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.

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Arterial oxygen tension, carbon dioxide tension, intrapulmonary shunt fraction (venous admixture %) and Vd/Vt (dead space to tidal volume ratio) in the newborn piglets of 4 groups at 0, 3, and 6 hr of experiment.CON: control group; PCON: E. coli pneumonia control; PNO: E. coli pneumonia with 10 ppm nitric oxide inhalation; PNANO: E. coli pneumonia with added nitric oxide inhalation to L-NAME pretreatment (10 mg/kg). Data represent mean±standard deviation. *p<0.05 compared to CON, †p<0.05 compared to PCON, ‡p<0.05 compared to PNO.
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Figure 3: Arterial oxygen tension, carbon dioxide tension, intrapulmonary shunt fraction (venous admixture %) and Vd/Vt (dead space to tidal volume ratio) in the newborn piglets of 4 groups at 0, 3, and 6 hr of experiment.CON: control group; PCON: E. coli pneumonia control; PNO: E. coli pneumonia with 10 ppm nitric oxide inhalation; PNANO: E. coli pneumonia with added nitric oxide inhalation to L-NAME pretreatment (10 mg/kg). Data represent mean±standard deviation. *p<0.05 compared to CON, †p<0.05 compared to PCON, ‡p<0.05 compared to PNO.

Mentions: PaO2 values in all groups, at the start of experiment, were in excess of 500 mmHg; the final PaO2 value was 460±28 mmHg in the surgical control animals (CON). Bacterial instillation through the trachea induced a progressive and significant decrease in the PaO2 level, which was 178±40 mmHg in the PCON animals at the end of experiment (p<0.01, by one-way repeated-measures ANOVA). NO inhalation ameliorates the progressive decrease in PaO2 in infected animals (PNO) (360±27 mmHg at the end of experiment, p<0.05 vs. PCON and CON). Pretreatment with L-NAME, before NO inhalation, (PNANO) completely prevented the progressive decrease in PaO2 (412±26 mmHg at 6 hr, p not significant by one-way repeated-measures ANOVA; p not significant vs. CON, p<0.05 vs. PCON) (Fig. 3).


Pretreatment with N-nitro-L-arginine methyl ester improved oxygenation after inhalation of nitric oxide in newborn piglets with Escherichia coli pneumonia and sepsis.

Chang YS, Kang S, Ko SY, Park WS - J. Korean Med. Sci. (2006)

Arterial oxygen tension, carbon dioxide tension, intrapulmonary shunt fraction (venous admixture %) and Vd/Vt (dead space to tidal volume ratio) in the newborn piglets of 4 groups at 0, 3, and 6 hr of experiment.CON: control group; PCON: E. coli pneumonia control; PNO: E. coli pneumonia with 10 ppm nitric oxide inhalation; PNANO: E. coli pneumonia with added nitric oxide inhalation to L-NAME pretreatment (10 mg/kg). Data represent mean±standard deviation. *p<0.05 compared to CON, †p<0.05 compared to PCON, ‡p<0.05 compared to PNO.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2721948&req=5

Figure 3: Arterial oxygen tension, carbon dioxide tension, intrapulmonary shunt fraction (venous admixture %) and Vd/Vt (dead space to tidal volume ratio) in the newborn piglets of 4 groups at 0, 3, and 6 hr of experiment.CON: control group; PCON: E. coli pneumonia control; PNO: E. coli pneumonia with 10 ppm nitric oxide inhalation; PNANO: E. coli pneumonia with added nitric oxide inhalation to L-NAME pretreatment (10 mg/kg). Data represent mean±standard deviation. *p<0.05 compared to CON, †p<0.05 compared to PCON, ‡p<0.05 compared to PNO.
Mentions: PaO2 values in all groups, at the start of experiment, were in excess of 500 mmHg; the final PaO2 value was 460±28 mmHg in the surgical control animals (CON). Bacterial instillation through the trachea induced a progressive and significant decrease in the PaO2 level, which was 178±40 mmHg in the PCON animals at the end of experiment (p<0.01, by one-way repeated-measures ANOVA). NO inhalation ameliorates the progressive decrease in PaO2 in infected animals (PNO) (360±27 mmHg at the end of experiment, p<0.05 vs. PCON and CON). Pretreatment with L-NAME, before NO inhalation, (PNANO) completely prevented the progressive decrease in PaO2 (412±26 mmHg at 6 hr, p not significant by one-way repeated-measures ANOVA; p not significant vs. CON, p<0.05 vs. PCON) (Fig. 3).

Bottom Line: E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI.Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection.This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, 50 Ilwon-Dong, Gangnam-Gu, Seoul, Korea.

ABSTRACT
We evaluated the effects of a combined therapy of pre-blockade endogenous nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn piglets were randomized into 5 groups: control, E. coli pneumonia control, pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli pneumonia was induced via intratracheal instillation of Escherichia coli, which resulted in progressively decreased cardiac index and oxygen tension; increased pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and developed septicemia at the end of 6 hr experiment. iNO ameliorated the progressive hypoxemia and intrapulmonary shunting without affecting the PVRI. Only two of 8 animals with L-NAME pretreated pneumonia survived. Whereas when iNO was added to infected animals with L-NAME pretreatment, the progressive hypoxemia was abolished as a result of a decrease in intrapulmonary shunting without reverse of the high PVRI and systemic vascular resistance index induced by the L-NAME injection. This result suggests that a NOS blockade may be a possible supportive option for oxygenation by iNO treatment in neonatal Gram-negative bacterial pneumonia and sepsis.

Show MeSH
Related in: MedlinePlus