ROCK INHIBITION AMELIORATES CRITICAL LIMB ISCHEMIA BY DECREASING INFLAMMATION Aamal G. El-Waseif, Manar A. Nader, Hatem A. Salem, Sally L. Elshaer Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University
In the past, peripheral arterial disease (PAD) was neglected in studying; however, recently PAD has had great attention because of its consequences of disability and cardiovascular morbidity and mortality. The present treatment for critical limb ischemia (CLI) is endovascular or surgical revascularization and there is no effective pharmacotherapy for the treatment or prevention of CLI. Therefore, the goal of this study was to establish experimental model of hind limb ischemia (HLI) in mice, investigate the effects of fasudil, a ROCK inhibitor, on HLI and demonstrate the possible involved mechanisms. In the present study, surgical unilateral HLI of left foot in mice, CLI simulation, was achieved by ligation and transection of the femoral artery and fasudil 10 mg/kg/day or 25 mg/kg/day was intraperitoneally injected for two weeks after 24 hours from surgery. Treatment with fasudil by different doses may have a promising modulation on CLI likely via attenuation of the inflammation revealed by reduction of TNF-α level. Because of this result, we hope that the findings of present study would give a cause for future investigations to explore the therapeutic potential of fasudil in the mitigation of CLI.