Effects of inhaled nitric oxide on pulmonary hemodynamics in a porcine model of endotoxin shock.
OBJECTIVE
To evaluate the effects of inhaled nitric oxide (NO) on pulmonary circulation in a porcine endotoxin shock model.


METHODS
Prospective, randomized trial.


METHODS
Laboratory at a large university medical center.


METHODS
Twelve pathogen-free pigs weighing 15 to 31 kg.


METHODS
After surgical preparation, all pigs received a 0.5 mg/kg endotoxin infusion over 30 mins. One hour after the start of endotoxin, NO inhalation (40 ppm) was initiated in six pigs, whereas the six remaining pigs served to control the progression of shock in this model. Consecutive changes in systemic and pulmonary hemodynamics, including characteristic resistance, vascular compliance, peripheral vascular resistance, and inductance, were continuously assessed during the experimental protocol using a four-element Windkessel model of the pulmonary circulation.


RESULTS
Endotoxin insult resulted in a biphasic pulmonary artery pressure increase from 14 +/- 2 to 32 +/- 4 mm Hg. Inhaled NO reversed the resistance to blood flow in small pulmonary arteries from 596 +/- 69 to 424 +/- 36 dyne-sec/ cm5. In contrast, the vascular capacitance of the entire pulmonary circuit, which decreased from 2.4 +/- 0.2 to 0.8 +/- 0.1 mL/mm Hg throughout endotoxin challenge, remained insensitive to NO administration.


CONCLUSIONS
In endotoxin-induced pulmonary hypertension, inhaled NO may function as a modulator of distal pulmonary arterial tone but fails to act as a regulator of larger capacitance pulmonary vessels.
Lambermont
B
B
Hemodynamics Research Laboratory (HemoLiege), University of Liege, Belgium. b.lambermont@chu.ulg.ac.be
D'Orio
V
V
Kolh
P
P
Gérard
P
P
Marcelle
R
R
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D009569:Nitric Oxide / Q000627:therapeutic use*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects*; D011897:Random Allocation; D012772:Shock, Septic / Q000150:complications* / Q000188:drug therapy; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide