A Comparison of Free Radical-Induced Vascular and Skeletal Muscle Damage in Immunocompetent and Neutropenic Rats

Abstract

Intraarterial infusion of the free radical donor tert. -butyl-hydroperoxide (tert.-BuOOH) into one extremity of the rat induces vascular permeability and considerable skeletal muscle damage. However, it remains unclear what the role of polymorphonuclear neutrophils (PMNs) is in oxidative stress-related processes. Therefore, we investigated possible differences between neutropenic and normal animals in this model. Neutropenia was induced in male rats by intraperitoneal administration of cyclophosphamide. tert.-BuOOH was continuously infused intraarterially into one hindlimb of normal or neutropenic nonanesthetized rats for 24 h. The control neutropenic rats were infused with the same volume of saline. After the infusion, 99mTc-IgG was administered intravenously followed by scintigraphic imaging analysis of the left/right uptake ratio of the hindlimbs and by gamma counting of the tissue samples of the gastrocnemius and gluteus maximus muscles. Samples of these muscles were analyzed by light microscopy. The uptake ratios were significantly increased in the normal and neutropenic tert.-BuOOH-infused animals as compared with the saline-infused neutropenic rats (P < 0.05). The uptake ratios were significantly higher in normal than in neutropenic tert.-BuOOH-infused rats (P < 0.05). Histological analysis of the saline infused skeletal muscles showed unaffected skeletal muscles with intact arterioles and arteries. In the gastrocnemius and gluteus maximus muscles of the normal tert. -BuOOH-infused and neutropenic rats, similar morphological damage was observed. PMNs can increase, to some extent, the vascular permeability of the free radical damaged small arteries and arterioles of a tert.-BuOOH-infused hindlimb. However, in the present animal model, tert.-BuOOH alone can induce oxidative stress-related abnormalities with skeletal muscle tissue damage that is mainly independent of the presence of PMNs.