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-NAMEpretreated 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.
Treatment Outcome ; Swine ; Survival Rate ; Sepsis/diagnosis/drug therapy/physiopathology ; Pulmonary Gas Exchange/*drug effects ; Premedication/*methods ; Pneumonia, Bacterial/diagnosis/*drug therapy/physiopathology ; Oxygen Consumption/*drug effects ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide/*administration & dosage ; NG-Nitroarginine Methyl Ester/*administration & dosage ; Injections, Intravenous ; Escherichia coli Infections/diagnosis/*drug therapy/physiopathology ; Drug Therapy, Combination ; Animals, Newborn ; Animals ; Administration, Inhalation

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-NAMEpretreated 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.
Treatment Outcome ; Swine ; Survival Rate ; Sepsis/diagnosis/drug therapy/physiopathology ; Pulmonary Gas Exchange/*drug effects ; Premedication/*methods ; Pneumonia, Bacterial/diagnosis/*drug therapy/physiopathology ; Oxygen Consumption/*drug effects ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide/*administration & dosage ; NG-Nitroarginine Methyl Ester/*administration & dosage ; Injections, Intravenous ; Escherichia coli Infections/diagnosis/*drug therapy/physiopathology ; Drug Therapy, Combination ; Animals, Newborn ; Animals ; Administration, Inhalation