EFFECTS OF OXYGEN-TENSION AND GLUCOSE-CONCENTRATION ON ISCHEMIC-INJURY IN VENTILATED FERRET LUNGS

In the ventilated ischemic lung, oxygen tension will increase at a tim e when glucose depletion may impair antioxidant defenses, thereby pred isposing the lung to injury mediated by oxygen radicals. In the unvent ilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxy gen tension and glucose concentration on ischemic injury in isolated f erret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (K(f)) and osmot ic reflection coefficient for albumin (sigma(alb)) after 3 h of normot hermic (37-degrees-C) ischemia without reperfusion. Lungs were ventila ted with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flu shed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxiano su bstrate) (n = 6 for each condition). K(f) and sigma(alb) in hyperoxia- no substrate group did not differ from values in minimally ischemic no rmoxic normoglycemic ferret lungs. Without glucose, ischemic injury wa s worse in anoxic than in hyperoxic lungs. With glucose, ischemic inju ry was worse in hyperoxic than in anoxic lungs. Glucose exacerbated in jury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glu cose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of th is injury.