Irwin DC, Subudhi AW, Klopp L, Peterson D, Roach R, Monnet E. Pulmonary edema induced by cerebral hypoxic insult in a canine model. Aviat Space Environ Med 2008; 79:472–8. Introduction: The mechanisms of noncardiogenic pulmonary edema syndromes, such as neurogenic and high-altitude pulmonary edema, remain unclear even after years of study. Previous attempts to develop an animal model for these illnesses have used increased intracranial pressure or whole-body hypoxia. We hypothesized that a cerebral insult induced with a venous hypoxic blood infusion to the brain would trigger neurogenic pulmonary edema in a canine model. Methods: We measured indices of pulmonary edema, hemodynamics, norepinephrine (NE), and epinephrine values in anesthetized adult Walker hounds in which the brain was perfused for 2 h with either venous blood (venous perfused brain, VPB) or arterial blood (arterial perfused brain, APB) while maintaining normoxic pulmonary and systemic circulations. Normal cerebral perfusion was then reinstated for an additional 2-h period before euthanasia. Results: VPB animals showed a greater fall in arterial Po₂ and S_ao₂ and higher peak plasma NE compared to APB. On necropsy, VPB animals had greater lung wet-to-dry weight ratios compared to APB. Histological analyses revealed areas of marked alveolar infiltration of neutrophils and macrophages, acute hemorrhage, congestion, and alveolar edema in the VPB animals. Discussion: This study supports the hypothesis that a cerebral insult from venous hypoxic blood can induce pulmonary edema. This method yields a promising approach to the study of noncardiogenic pulmonary edema syndromes.