Effects of 100% oxygen on lung vascular function in awake sheep

Publisher Website
Google Scholar
Abstract
The time course of pulmonary toxicity during continuous breathing of 100% O2 in adult sheep was studied. Sheep were prepared for chronic measurement of vascular pressures, cardiac output, gas exchange and for collection of lung lymph. Tracheostomies allowed accurate delivery of either 100% O2 compressed air or hypoxic gas. Six sheep breathed 100% O2 for 72-96 h, and 4 sheep breathed compressed air for 96 h. In addition to hypoxic challenges [fractional concentration of inspired O2 (FIO2) = 0.12], some sheep received prostaglandin H2(PGH2)-analogue infusions to further assess pulmonary vascular reactivity. Lung lymph and blood chemotactic activity were measured by granulocyte migration in modified Boyden chambers. Postmortem lung water content and light microscopy were used to measure pulmonary edema. All sheep breathing 100% O2 died between 72 (n = 2) and 96 h (n = 4). Sheep breathing O2 demonstrated lung toxicity by measurements of a 4-fold increase in flow of protein-rich lung lymph, increased alveolar-arterial difference in PO2 [O2 partial pressure] (G 20 Torr on FIO2 = 0.21) and hypercapnic acidemia, and a mean extravascular lung water/dry lung weight of 5.7 (controls = 3.3) and histological evidence of interstitial and alveolar edema. Chemotactic activity in lung lymph at base line increased 8-fold within 72-96 h of O2 breathing. In sheep breathing O2, the hypoxic pressor response decreased by 50% at 48 h, and by 72-96 h there was a total absence of hypoxic vasoconstriction. There was no increase in lung lymph prostacyclin metabolite, and sodium meclofenamate did not restore the pressor response. In sheep breathing compressed air, none of these changes in pulmonary vascular reactivity, lymph flow or chemotactic activity occurred. Prolonged breathing of pure O2 causes pulmonary edema by increasing lung vascular permeability and that respiratory failure results from both edema and loss of pulmonary vascular reactivity.