A comparison of free radical-induced vascular and skeletal muscle damage in immunocompetent and neutropenic rats

Background Intraarterial infusion of the free radical donor tert.-butyl-hyd roperoxide (tert.-BuOOH) into one extremity of the rat induces vascular per meability and considerable skeletal muscle damage. However, it remains uncl ear what the role of polymorphonuclear neutrophils (PMNs) is in oxidative s tress-related processes. Therefore, we investigated possible differences be tween neutropenic and normal animals in this model. Methods, Neutropenia was induced in male rats by intraperitoneal administra tion of cyclophosphamide. tert.-BuOOH was continuously infused intraarteria lly 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, Tc-99m-IgG was administered intravenously followed by scintigraphic imaging analysis of the left/right uptake ratio of the hindl imbs and by gamma counting of the tissue samples of the gastrocnemius and g luteus maximus muscles. Samples of these muscles were analyzed by light mic roscopy. Results. The uptake ratios were significantly increased in the normal and n eutropenic 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). Histologica l analysis of the saline infused skeletal muscles showed unaffected skeleta l muscles with intact arterioles and arteries. In the gastrocnemius and glu teus maximus muscles of the normal tert.-BuOOH-infused and neutropenic rats , similar morphological damage was observed Conclusions. PMNs can increase, to some extent, the vascular permeability o f the free radical damaged small arteries and arterioles of a tert.-BuOOH-i nfused hindlimb. However, in the present animal model, tert.-BuOOH alone ca n induce oxidative stress-related abnormalities with skeletal muscle tissue damage that is mainly independent of the presence of PMNs. (C) 1999 Academ ic Press.