Distant effects of nitric oxide inhalation in endotoxemic pigs.
OBJECTIVE
Inhalation of nitric oxide (INO) has distant effects. By a blood- borne factor, INO down-regulates endogenous nitric oxide production in healthy pig lungs, resulting in vasoconstriction in lung regions not directly reached by INO. The aim of this study was to investigate whether INO has distant effects in endotoxemic pig lungs. The hypothesis was that INO down-regulates endogenous NO production in lung regions not reached by INO.


METHODS
Prospective, randomized animal study.


METHODS
University hospital research laboratory.


METHODS
Twenty-two pairs of domestic pigs.


METHODS
Cross-circulation was established in 22 pairs of anesthetized pigs. Nine pairs received endotoxin (control group) and 13 pairs received endotoxin, with one pig inhaling NO (80 ppm) and one pig receiving blood from that pig (NO-blood recipient group).


RESULTS
NO in exhaled air, NO synthase activity in lung tissue, endothelin-1 in the blood, ETA and ETB receptor immunoreactivity in lung tissue, vital parameters, and blood gases were measured. Endotoxin per se increased NO in exhaled air by 100% compared to baseline (control group). In the NO-blood recipient group, i.e., pigs receiving blood from the NO-inhaling pigs, NO in exhaled air increased by 300% (p = .03). The Ca-dependent NO synthase activity was higher in these pigs (p = .02), indicating increased endogenous NO production. The ET B receptor immunoreactivity was higher in the NO-blood recipient group (p = .004).


CONCLUSIONS
As opposed to findings in healthy pigs, INO in endotoxemic pigs causes an increase in endogenous NO production in lung regions not reached by INO. Increased NO production in nonventilated lung regions may cause vasodilatation, counteracting the INO-induced increase in blood flow to the ventilated lung regions.
Nilsson
Manja C A
MC
Department of Anesthesiology and Intensive Care, Uppsala University, Uppsala.
Hambraeus-Jonzon
Kristina
K
Hambraeus-Jonon
Kristina
K
Lattuada
Marco
M
Chen
Luni
L
Li
Ren
R
Alving
Kjell
K
Wiklund
Peter
P
Hedenstierna
Goran
G
Fredén
Filip
F
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood* / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D011336:Probability; D011652:Pulmonary Circulation / Q000187:drug effects*; D011863:Radioimmunoassay; D011897:Random Allocation; D012016:Reference Values; D015996:Survival Rate; D034421:Sus scrofa; D013552:Swine
D019332:Endothelin-1; D004731:Endotoxins; D009569:Nitric Oxide