• Lars J Bjertnaes, Roy McGuire, Jeffery Jodoin, Andrew L Salzman, Lillian D Traber, Daniel J Passerini, Daniel J Smith, Csaba Szabo, and Daniel L Traber.
• Department of Anesthesiology, University of Tromsø, Tromsø, Norway.
• Crit. Care Med. 2005 Mar 1;33(3):616-22.

ObjectiveTo 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.DesignProspective, randomized, controlled study in awake sheep.SettingInvestigational intensive care unit of a university medical center.SubjectsThirteen instrumented merino ewes weighing 36 +/- 0.9 kg underwent a hemodynamic study 1 wk postoperatively.InterventionsOn 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 ResultsInhaled 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.ConclusionsIn 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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