Dose-dependent response to IFN-gamma in muscle flap microcirculation

In this study, the authors attempted to determine the effects of intraarterial administration of various doses of Interferon-gamma (IFN-gamma) on microcirculation in a rat muscle flap model. In Group 1 (control), 0.6 ml vehicle solution-PBS-BSA, in Group 2 0.6 ml IFN-gamma (25 ng/ml), in Group 3 0.6 ml IFN-gamma (50 g/ml), in Group 4 0.6 ml IFN-gamma (100 g/ml), were injected. The diameter of the cremaster arterioles and venules, red blood cell velocities, the number of rolling leukocytes and lymphocytes, sticking leukocytes and lymphocytes, capillary perfusion, and endothelial edema index were evaluated. Deterioration of flow hemodynamics was confirmed by a significant decrease in flow velocity in the main artery (A1) (47 percent in Group 3 and 65 percent in Group 4). All dosages of IFN-gamma caused a statistically significant decrease in rolling leukocytes, but this effect was more obvious in the 25 ng/ml group. Injury to the vascular endothelium was confirmed by a two-fold increase in transmigrating leukocytes in the 100 ng/ml group. This was accompanied by 60 percent and 75 percent drops in capillary perfusion, and by 12 percent and 24 percent drops in the endothelial edema index in Groups 3 and 4, respectively. The results indicate that direct intraarterial administration of IFN-gamma in doses higher than 25 ng/ml may be toxic to muscle flaps.