Combined burn and smoke inhalation injury impairs ovine hypoxic pulmonary vasoconstriction*

Objective: To examine the effects of combined bum and smoke inhalation injury on hypoxic pulmonary vasoconstriction, 3-nitrotyrosine formation, and respiratory function in adult sheep. Design: Prospective, placebo-controlled, randomized, single-blinded trial. Setting: University research laboratory. Subjects: Twelve chronically instrumented ewes. Interventions: 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 bum 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. Measurements and Main Results: Combined bum and smoke inhalation was associated with increased expression of inducible nitric oxide (NO) synthase, elevated NO 2 /NO 3 (NOx) plasma levels (12 hrs, sham, 6.2 ± 0.6; injury, 16 ± 1.6 μmol·L -1 ; p