Combined burn and smoke inhalation injury impairs ovine hypoxic pulmonary vasoconstriction.
OBJECTIVE
To examine the effects of combined burn and smoke inhalation injury on hypoxic pulmonary vasoconstriction, 3-nitrotyrosine formation, and respiratory function in adult sheep.


METHODS
Prospective, placebo-controlled, randomized, single-blinded trial.


METHODS
University research laboratory.


METHODS
Twelve chronically instrumented ewes.


METHODS
Following a baseline measurement, sheep were randomly allocated to either healthy controls (sham) or the injury group, subjected to a 40%, third-degree body surface area burn and 48 breaths of cotton smoke according to an established protocol (n = 6 each). Hypoxic pulmonary vasoconstriction was assessed as changes in pulmonary arterial blood flow (corrected for changes in cardiac index) in response to left lung hypoxic challenges performed at baseline and at 24 and 48 hrs postinjury.


RESULTS
Combined burn and smoke inhalation was associated with increased expression of inducible nitric oxide (NO) synthase, elevated NO2/NO3 (NOx) plasma levels (12 hrs, sham, 6.2 +/- 0.6; injury, 16 +/- 1.6 micromol.L; p < .01) and increased peroxynitrite formation, as indicated by augmented lung tissue 3-nitrotyrosine content (30 +/- 3 vs. 216 +/- 8 nM; p < .001). These biochemical changes occurred in parallel with pulmonary shunting, progressive decreases in Pao2/Fio2 ratio, and a loss of hypoxic pulmonary vasoconstriction (48 hrs, -90.5% vs. baseline; p < .001). Histopathology revealed pulmonary edema and airway obstruction as the morphologic correlates of the deterioration in gas exchange and the increases in airway pressures.


CONCLUSIONS
This study provides evidence for a severe impairment of hypoxic pulmonary vasoconstriction following combined burn and smoke inhalation injury. In addition to airway obstruction, the loss of hypoxic pulmonary vasoconstriction may help to explain why blood gases are within physiologic ranges for a certain time postinjury and then suddenly deteriorate.
Westphal
Martin
M
Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
Cox
Robert A
RA
Traber
Lillian D
LD
Morita
Naoki
N
Enkhbaatar
Perenlei
P
Schmalstieg
Frank C
FC
Hawkins
Hal K
HK
Maybauer
Dirk M
DM
Maybauer
Marc O
MO
Murakami
Kazunori
K
Burke
Ann S
AS
Westphal-Varghese
Beena B
BB
Rudloff
Helen E
HE
Salsbury
John R
JR
Jodoin
Jeffrey M
JM
Lee
Steve
S
Traber
Daniel L
DL
D000818:Animals; D002056:Burns / Q000401:mortality / Q000503:physiopathology*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009104:Multiple Trauma / Q000401:mortality / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D012756:Sheep; D016037:Single-Blind Method; D015208:Smoke Inhalation Injury / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014661:Vasoconstriction
D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II