A NOVEL ANIMAL-MODEL TO EVALUATE OXYGEN-DERIVED FREE-RADICAL DAMAGE IN SOFT-TISSUE

We present a novel animal model which allows the continuous intra-arte rial infusion in one hindlimb of nan-anaesthetized rats, without induc ing ischemia. Using this model the effect of continuous infusion (1ml/ h) for 24 h with tert-butylhydroperoxide (tert-BuOOH) at a concentrati on of 25mM on soft tissue of the left hind limb was studied and compar ed to the effect of saline infusion (control group). The tert-BuOOH-in fused foot showed increased skin temperature, increased circumference, redness of the plantar skin, impaired function and increased pain sen sation, while in the contralateral foot and in rats only perfused with saline these signs of inflammation were absent (p < 0.01). Histologic al analysis of the left gastrocnemius muscle showed edema, muscle cell degeneration with a patchy distribution pattern and vascular damage. All these features increased in severity from 4 to 24 h of tert-BuOOH infusion. After 24 h of tert-BuOOH infusion infiltration of neutrophil s in the interstitium was observed. Vascular permeability, expressed a s left to right gastrocnemius muscle Tc-99m-IgG uptake ratio, was simi larly increased after 4 h (2.09 +/- 0.26) and 12 h (2.04 +/- 0.08) of tert-BuOOH infusion compared to saline (1.05 +/- 0.08) (p < 0.001), an d further increased after 24 h (3.84 +/- 0.13): (p < 0.001). In this a nimal model free radical-related soft tissue damage was induced, by co ntinuous infusion of tert-BuOOH, followed by increasing necrosis and v ascular permeability in skeletal muscle coinciding with neutrophilic i nfiltration.