Oxidative stress and induction of non‐cardiogenic pulmonary edema following cerebral hypoxia in a canine model

Abstract

Neurogenic pulmonary edema (NPE) is a non‐cardiogenic form of pulmonary edema associated with stroke, traumatic brain injury and seizure. NPE is a public health concern due to high morbidity and mortality, yet the mechanism(s) are unknown.HypothesisCerebral hypoxia, even in the absence of systemic hypoxia, is sufficient to induce pulmonary edema, oxidative stress and compensatory antioxidant mechanisms.MethodsUsing an updated Moss's model, 9 Walker hounds were randomly assigned to cerebral hypoxemia (SaO2 ~55%) with systemic normoxia (SaO2 ~90%) (CH; n=6), or cerebral and systemic normoxia (SaO2 ~90%) (Sham; n=3). Femoral venous (CH) or arterial (Sham) perfusate was delivered from a cardiopulmonary bypass circuit to the brain. Wet to dry lung weight ratios were assessed as an index of pulmonary edema, lipid peroxidation was assessed as an indicator of oxidative stress, and brain and lung compensatory antioxidants were assessed with immunoblotting.ResultsLung wet:dry weight was greater in the CH compared to sham. Lipid peroxidation was greater in CH and was accompanied by increased compensatory antioxidants (hemeoxygenase‐1, NAD(P)H quinone oxidoreductase‐1).ConclusionBrain hypoxemia, despite systemic normoxia, is associated with lipid peroxidation and compensatory antioxidant enzymes, suggesting oxidative stress could contribute to neurogenic pulmonary edema. DARPA N66001‐10‐C‐2134