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 Citations (Scopus)

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 2005
Externally publishedYes

Fingerprint

Vascular Resistance
Sheep
Nitric Oxide
Hemodynamics
Sepsis
Gases
Lung
Tracheotomy
Plasma Exchange
Nitric Oxide Donors
Nebulizers and Vaporizers
Nitrites
Artificial Respiration
Nitrates
Pseudomonas aeruginosa
Pulmonary Artery
Intensive Care Units
Arterial Pressure
methyl-N-2-dimethylaminoethyl-3-aminoproprionid-nitric oxide
Bacteria

Keywords

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

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Bjertnaes, L. J., McGuire, R., Jodoin, J., Salzman, A. L., Traber, L. D., Passerini, D. J., ... 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

Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep. / Bjertnaes, Lars J.; McGuire, Roy; Jodoin, Jeffery; Salzman, Andrew L.; Traber, Lillian D.; Passerini, Daniel J.; Smith, Daniel J.; Szabo, Csaba; Traber, Daniel L.

In: Critical Care Medicine, Vol. 33, No. 3, 03.2005, p. 616-622.

Research output: Contribution to journalArticle

Bjertnaes, LJ, McGuire, R, Jodoin, J, Salzman, AL, Traber, LD, Passerini, DJ, Smith, DJ, Szabo, C & Traber, DL 2005, 'Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep', Critical Care Medicine, vol. 33, no. 3, pp. 616-622. https://doi.org/10.1097/01.CCM.0000156282.22495.A1
Bjertnaes, Lars J. ; McGuire, Roy ; Jodoin, Jeffery ; Salzman, Andrew L. ; Traber, Lillian D. ; Passerini, Daniel J. ; Smith, Daniel J. ; Szabo, Csaba ; Traber, Daniel L. / Nebulized nitric oxide/nucleophile adduct reduces pulmonary vascular resistance in mechanically ventilated septicemic sheep. In: Critical Care Medicine. 2005 ; Vol. 33, No. 3. pp. 616-622.
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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.",
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AU - McGuire, Roy

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AU - Salzman, Andrew L.

AU - Traber, Lillian D.

AU - Passerini, Daniel J.

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KW - Sepsis

KW - Vascular resistance

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