Direct Detection of Free Radical Generation in anIn VivoModel of Acute Lung Injury

Abstract

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.

Free Radicals and Medicine

“…Cotton smoke formed radical adduct concentrations similar to those caused by 2.5 atm of oxygen (Yamaguchi et al‚ 1992). Formation of a burst of PBN radical adducts by a brief exposure to cigarette smoke required pretreatment by bacterial endotoxin (Murphy et al‚ 1991).…”

“…Both the in vitro effects of this smoke and the use of ESR in these studies have been extensively reviewed (Pryor 1992). Smoke inhalation by rabbits formed unidentified PBN radical adducts in plasma (Yamaguchi et al‚ 1992;Murphy et al‚ 1991). Cotton smoke formed radical adduct concentrations similar to those caused by 2.5 atm of oxygen (Yamaguchi et al‚ 1992).…”

Cholesterol, But Not Cigarette Smoke, Decreases Rabbit Carotid Artery Relaxation

“…Cigarette smoke can also activate the release of oxygen free-radicals, which can destroy the endothelium and decrease nitric oxide production directly. 23 The antioxidant vitamin C has been shown to markedly improve endothelium-dependent acetylcholine-mediated vasorelaxation in human forearm vessels of chronic smokers. 24 This would suggest that oxygen free-radicals are mediating the subsequent endothelial dysfunction found after exposure to cigarette smoke as well.…”

Lesson of the week: Central venous air embolism causing pulmonary oedema mimicking left ventricular failure

“…Electron spin resonance spectroscopy has been used in mice to show the role of free radicals derived from oxygen in acute lung injury by detecting increased production of free radicals at the time of increased permeability of the alveolar-capillary barrier 7. In vivo the alveolar-capillary barrier consists of two juxtaposed surfaces: the capillary endothelium and the alveolar epithelium.…”