Abstract
Summary: In newborn lambs, lung vascular permeability to protein increases after 3 days of continuous oxygen breathing. We studied six unanesthetized lambs that were less than 1 month old to see if intramuscular administration of vitamin E, an antioxidant, would prevent or lessen the severity of this oxygen-induced lung injury. To assess lung fluid balance, we measured pulmonary arterial and left atrial pressures, lung lymph flow, and concentrations of protein in lymph and plasma of lambs that received intramuscularly vitamin E, 20 mg/kg body weight, for 2 days before the experiment and then daily as they breathed pure oxygen. Despite a 10-fold increase in the plasma concentration of vitamin E (2.5 ± 0.4 μg/ml to 24.4 ± 2.9 μg/ml), pulmonary microvascular permeability to protein increased in all of the lambs within 3 days of sustained hyperoxia: lung lymph flow tripled, the concentration of protein in lymph increased, and the ratio of the albumin concentration to the globulin concentration in lymph, relative to that in plasma, decreased. Vascular pressures did not change significantly during the course of oxygen breathing. In four lambs, we injected [125I]-albumin into the right atrium and determined the time for specific activity in lymph to reach one-half that of plasma (half-equilibration). The time averaged 146 ± 21 min before oxygen breathing and 46 ± 7 min after 3 days to oxygen. These data provide clearcut evidence that severe endothelial injury occurred. All six lambs died of respiratory failure after 4 days or less in oxygen. Extra-vascular lung water per g of dry lung tissue was significantly greater in these lambs than in control lambs (5.88 ± 0.46 versus 4.72 ± 0.14).
These results show that sustained hyperoxia increased trans-vascular movement of fluid and protein into the pulmonary inter-stitium and caused edema. The outcome of these studies was almost identical to that of previous experiments to which lambs continuously breathed oxygen but did not receive vitamin E. We conclude that vitamin E was not effective to protecting the lungs from microvascular injury.
Speculation: These results suggest that administration of vitamin E to animals that are not deficient in vitamin E does not protect them from oxygen-induced lung injury.
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Hansen, T., Hazinski, T. & Bland, R. Vitamin E Does Not Prevent Oxygen-Induced Lung Injury in Newborn Lambs. Pediatr Res 16, 583–587 (1982). https://doi.org/10.1203/00006450-198207000-00020
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DOI: https://doi.org/10.1203/00006450-198207000-00020