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


METHODS
Prospective, randomized, controlled study in awake sheep.


METHODS
Investigational intensive care unit of a university medical center.


METHODS
Thirteen instrumented merino ewes weighing 36 +/- 0.9 kg underwent a hemodynamic study 1 wk postoperatively.


METHODS
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.


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.
Bjertnaes
Lars J
LJ
Department of Anesthesiology, University of Tromsø, Tromsø, Norway.
McGuire
Roy
R
Jodoin
Jeffery
J
Salzman
Andrew L
AL
Traber
Lillian D
LD
Passerini
Daniel J
DJ
Smith
Daniel J
DJ
Szabo
Csaba
C
Traber
Daniel L
DL
D000336:Aerosols; D000818:Animals; D004123:Dimethylamines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000494:pharmacology*; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011897:Random Allocation; D012121:Respiration, Artificial; D018805:Sepsis / Q000628:therapy*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*
D000336:Aerosols; D004123:Dimethylamines; D020030:Nitric Oxide Donors; C498979:methyl-N-2-dimethylaminoethyl-3-aminoproprionid-nitric oxide; D009569:Nitric Oxide