Pulmonary effects of ischemic limb reperfusion : evidence for a role for oxygen-derived radicals

OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion. DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables. SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay. A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen. Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors.