Limits...
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.

Show MeSH

Related in: MedlinePlus

Scheme of the experimental protocol. L-NAME, administration of N-nitro-L-arginine methyl ester; E.coli/Saline, intratracheal instillation of Escherichia coli or Saline; iNO, administration of inhaled nitric oxide; Ventilator re-adjustment, Ventilator settings were changed to peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, peak end expiratory pressure (PEEP) 4 cmH2O, inspiratory time (IT) 0.6 sec. Animals in PNA were not included for the results because only two of eight survived. Measurement of variables was recorded hourly.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2721948&req=5

Figure 1: Scheme of the experimental protocol. L-NAME, administration of N-nitro-L-arginine methyl ester; E.coli/Saline, intratracheal instillation of Escherichia coli or Saline; iNO, administration of inhaled nitric oxide; Ventilator re-adjustment, Ventilator settings were changed to peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, peak end expiratory pressure (PEEP) 4 cmH2O, inspiratory time (IT) 0.6 sec. Animals in PNA were not included for the results because only two of eight survived. Measurement of variables was recorded hourly.

Mentions: After surgery and stabilization, baseline measurements of arterial blood gases and hemodynamic parameters were recorded. Ventilator settings were changed to a peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, a peak end expiratory pressure (PEEP) 4 cmH2O and an inspiratory time (IT) of 0.6 sec. Animals were divided into five groups: 1) a sham operation control group (CON, n=6), 2) an E. coli pneumonia control (PCON, n=10), 3) a pneumonia and nitric oxide inhalation (PNO, n=10), 4) a N-nitro-L-arginine methyl ester (L-NAME) treated pneumonia (PNA, n=8) and 5) a L-NAME treated pneumonia followed by NO inhalation (PNANO, n=8). After baseline measurements of arterial blood gases, Escherichia coli pneumonia was induced in all animals except the CON group. Each anesthetized animal was placed in the supine position with the head elevated approximately 20 degrees and a 5-Fr. catheter was inserted through the endotracheal tube. The bacterial inoculum of Escherichia coli, EC69 strain (kind gift of Dr. Kwang Sik Kim, Johns Hopkins University, Baltimore, Maryland, U.S.A.) (17), 1×109 colony forming unit in 10 mL of 0.9% saline was instilled into the lung followed by a 10 mL bolus of air to disperse the bacteria into the distal lung. Piglets in the CON group were given 10 mL of 0.9% saline instead of the bacterial inoculum. The experimental protocols for each group are described in Fig. 1. L-NAME, a nonselective inhibitor of nitric oxide synthase was injected 30 min before bacterial instillation in the PNA and PNANO groups. Nitric oxide gas, 10 ppm inhalation, was started at 30 min after bacterial instillation and continued until the end of the experiment in the PNO and PNANO groups. The animals were maintained for 6 hr after the bacterial or saline instillations. Blood cultures were obtained, for each animal, at the end of experiment.


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)

Scheme of the experimental protocol. L-NAME, administration of N-nitro-L-arginine methyl ester; E.coli/Saline, intratracheal instillation of Escherichia coli or Saline; iNO, administration of inhaled nitric oxide; Ventilator re-adjustment, Ventilator settings were changed to peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, peak end expiratory pressure (PEEP) 4 cmH2O, inspiratory time (IT) 0.6 sec. Animals in PNA were not included for the results because only two of eight survived. Measurement of variables was recorded hourly.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Scheme of the experimental protocol. L-NAME, administration of N-nitro-L-arginine methyl ester; E.coli/Saline, intratracheal instillation of Escherichia coli or Saline; iNO, administration of inhaled nitric oxide; Ventilator re-adjustment, Ventilator settings were changed to peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, peak end expiratory pressure (PEEP) 4 cmH2O, inspiratory time (IT) 0.6 sec. Animals in PNA were not included for the results because only two of eight survived. Measurement of variables was recorded hourly.
Mentions: After surgery and stabilization, baseline measurements of arterial blood gases and hemodynamic parameters were recorded. Ventilator settings were changed to a peak inspiratory pressure (PIP) 30 cmH2O, rate 25/min, a peak end expiratory pressure (PEEP) 4 cmH2O and an inspiratory time (IT) of 0.6 sec. Animals were divided into five groups: 1) a sham operation control group (CON, n=6), 2) an E. coli pneumonia control (PCON, n=10), 3) a pneumonia and nitric oxide inhalation (PNO, n=10), 4) a N-nitro-L-arginine methyl ester (L-NAME) treated pneumonia (PNA, n=8) and 5) a L-NAME treated pneumonia followed by NO inhalation (PNANO, n=8). After baseline measurements of arterial blood gases, Escherichia coli pneumonia was induced in all animals except the CON group. Each anesthetized animal was placed in the supine position with the head elevated approximately 20 degrees and a 5-Fr. catheter was inserted through the endotracheal tube. The bacterial inoculum of Escherichia coli, EC69 strain (kind gift of Dr. Kwang Sik Kim, Johns Hopkins University, Baltimore, Maryland, U.S.A.) (17), 1×109 colony forming unit in 10 mL of 0.9% saline was instilled into the lung followed by a 10 mL bolus of air to disperse the bacteria into the distal lung. Piglets in the CON group were given 10 mL of 0.9% saline instead of the bacterial inoculum. The experimental protocols for each group are described in Fig. 1. L-NAME, a nonselective inhibitor of nitric oxide synthase was injected 30 min before bacterial instillation in the PNA and PNANO groups. Nitric oxide gas, 10 ppm inhalation, was started at 30 min after bacterial instillation and continued until the end of the experiment in the PNO and PNANO groups. The animals were maintained for 6 hr after the bacterial or saline instillations. Blood cultures were obtained, for each animal, at the end of experiment.

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