Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.
OBJECTIVE
Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension.


METHODS
Prospective, randomized, controlled study.


METHODS
Research laboratory.


METHODS
Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg.


METHODS
In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6).


RESULTS
Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05).


CONCLUSIONS
In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.
Brilli
R J
RJ
Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Krafte-Jacobs
B
B
Smith
D J
DJ
Passerini
D
D
Moore
L
L
Ballard
E T
ET
D000208:Acute Disease; D000280:Administration, Inhalation; D000336:Aerosols; D000599:Amino Acids, Diamino / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D008168:Lung / Q000098:blood supply; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
C110153:2-(dimethylamino)ethylputreanine-nitric oxide adduct; D000336:Aerosols; D000599:Amino Acids, Diamino; C110152:ethylputreanine-nitric oxide adduct; D009569:Nitric Oxide; D008706:Methemoglobin