Direct detection of free radical generation in an in vivo model of acute lung injury

Electron spin resonance (ESR) spectroscopy has been used to provide direct evidence that free radical production occurs in an in vivo model of acute lung injury. Two experimental groups of rabbits were given the spin trap alpha-phenyl N-tert.-butyl nitrone (PBN), together with endotoxin in the test group, and saline in the control group. Both groups were subsequently briefly ventilated with air containing cigarette smoke. Plasma samples from the endotoxin pretreated group showed a sudden burst of radical formation, detected as PBN spin adduct, which peaked in the first ten minutes after smoke exposure. No signals were detected in the control group. Permeability of the alveolar capillary barrier of the lung, measured by the clearance of 99mTc-DTPA, demonstrated significantly greater damage following smoke in the endotoxin primed animals than in the controls. Temporal studies suggest that this increase in permeability occurred after a burst of radical production. These studies provide supportive evidence for the hypothesis that endotoxin promotes the accumulation of a population of primed white cells within the lung, which when triggered by cigarette smoke, are able to generate a burst of free radicals which produce tissue damage and acute lung injury.