Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep

Lars J. Bjertnaes, Roy McGuire, Jeffery Jodoin, Andrew L. Salzman, Lillian D. Traber, Daniel J. Passerini, Daniel J. Smith, Csaba Szabo, Daniel L. Traber

    Research output: Contribution to journalArticle

    3 Scopus citations

    Abstract

    Objective: To study the effects of a novel, intermittently administered, aerosolized nitric oxide donor, methyl-N-2-dimethylaminoethyl-3-aminoproprionid/ nitric oxide (DMDE-NO), on pulmonary hemodynamic responses to sepsis. Design: Prospective, randomized, controlled study in awake sheep. Setting: Investigational intensive care unit of a university medical center. Subjects: Thirteen instrumented merino ewes weighing 36 ± 0.9 kg underwent a hemodynamic study 1 wk postoperatively. Interventions: On the day of the experiment, the sheep received a tracheotomy and mechanical ventilation was subsequently started. Pseudomonas aeruginosa bacteria were infused intravenously, beginning at time 0 hrs and continuing throughout the 48-hr experiment. The animals were randomly assigned to receive nebulized DMDE-NO 1 mg/kg, dissolved in 8 mL of saline (DMDE-NO group, n = 7), or nebulized saline alone (control group, n = 6) delivered by a nebulizer. The nebulizations started at 2, 6, 20, 24, and 43 hrs after the baseline, each time lasting for 1 hr. Measurements and Main Results: Inhaled aerosolized DMDE-NO reversibly reduced the sepsis-induced increase in pulmonary artery pressure by 13-17% and pulmonary vascular resistance index by 21-31% compared with the values registered before the administration of the drug. Systemic hemodynamics underwent an early hypodynamic phase followed by a gradual increase in cardiac index and a decrease in both mean arterial pressure and systemic vascular resistance index, but with no significant difference between groups. Gas exchange variables and plasma nitrite/nitrate did not differ significantly between groups either. Conclusions: In sheep, inhaled nebulized DMDE-NO reduces sepsis-induced changes in pulmonary hemodynamics with no change in systemic hemodynamics or gas exchange.

    Original languageEnglish (US)
    Pages (from-to)616-622
    Number of pages7
    JournalCritical care medicine
    Volume33
    Issue number3
    DOIs
    StatePublished - Mar 1 2005

    Keywords

    • Hemodynamics
    • Mechanical ventilation
    • Nitric oxide
    • Pulmonary hypertension
    • Sepsis
    • Vascular resistance

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine

    Fingerprint Dive into the research topics of 'Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep'. Together they form a unique fingerprint.

  • Cite this

    Bjertnaes, L. J., McGuire, R., Jodoin, J., Salzman, A. L., Traber, L. D., Passerini, D. J., Smith, D. J., Szabo, C., & Traber, D. L. (2005). Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep. Critical care medicine, 33(3), 616-622. https://doi.org/10.1097/01.CCM.0000156282.22495.A1