Neutrophil Activation in Ischemia-reperfusion Injury of the Lung

Activated neutrophils and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with ischemia reperfusion. This study tests whether postischemic reperfusion in the lung activates neutrophils and whether superoxide dismutase (SOD) could block this event. Ten anesthetized mongrel dogs underwent three hours of warm ischemia to their left lung followed by 120 minutes of reperfusion. Pulmonary venous blood was assayed for neutrophil hydrogen peroxide production and plasma thiobarbituric acid reactive materials (TBARM) immediately before (baseline) and during reperfusion. Neutrophil hydrogen peroxide production, as assayed flow cytometrically by dichlorofluorescein oxidation, was elevated significantly to 123.9 ± 21.1% of baseline at 30 minutes of reperfusion. Plasma TBARM was elevated significantly to 124.2 ± 23.6% of baseline at 60 minutes after reperfusion. However, in six animals which recieved human recombinant SOD (intravenously, 35000U/kg) at the onset of reflow, neither neutrophil hydrogen peroxide production nor plasma TBARM changed during reperfusion. Treatment with SOD was also associated with significant improvement in the recovery of lung function. In conclusion, these data demonstrate that post-ischemic lung reperfusion enhances neutrophil hydrogen peroxide and free radical production, and can be blocked by intravenous SOD