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 time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated 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 oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flushed 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, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.
Becker
P M
PM
Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Pearse
D B
DB
Sylvester
J T
JT
D000818:Animals; D005289:Ferrets; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000473:pathology; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology*; D008168:Lung / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011312:Pressure; D011652:Pulmonary Circulation; D012121:Respiration, Artificial; D015430:Weight Gain
D005947:Glucose; D010100:Oxygen