REQUIREMENTS FOR NEUTROPHIL PRODUCTS AND L-ARGININE IN ISCHEMIA-REPERFUSION INJURY

Ischemia followed by reperfusion in rat limb results in evidence of va scular injury in the limb as well as in the lung as measured by leakag e of [I-125]albumin and extravasation of [Cr-51] red blood cells. Vasc ular injury in lung and limb was proportional to the time of limb repe rfusion and was associated with accumulation of myeloperoxidase, as we ll as evidence of complement consumption. In this model, the rank orde r of protective interventions was. neutrophil depletion > catalase + s uperoxide dismutase = allopurinol > dimethylthiourea = dimethylsulfoxi de > deferoxamine = complement depletion. These data suggest that toxi c oxygen products of neutrophils are related to the development of vas cular injury. There was a reasonable correlation between protective ef fects of interventions and reduced tissue context of myeloperoxidase. Systemic treatment with the L-arginine antagonists, N(G)-monomethyl-L- arginine or nitro-L-arginine methyl ester, was also protective against vascular injury, suggesting that metabolic prodUCts Of L-arginine par ticipate in events leading to injury.