ABSTRACT
Critical limb ischemia is a state of advanced peripheral vascular disease resulting in paraesthesia, pain, tissue breakdown, gangrene and necrosis of the distal portion of the affected limb. The effects of chronic ischemia on resistance artery function have yet to be fully determined. Endothelial function in isolated arteries from patients with critical limb ischemia were investigated. Immediately following amputation, arteries were isolated from proximal and distal sites from both subcutaneous and skeletal muscle vascular beds. The distal arteries were harvested from the ischemic portion of the leg. Whereas the proximal arteries were harvested from a non-ischaemic site and served as internal controls. Isolated resistance-sized arteries were studied on a pressure myograph. Endothelium-dependent relaxation were significantly impaired in both subcutaneous and skeletal muscle arteries from the distal ischaemic sites when compared with the proximal, non-ischaemic arteries. In subcutaneous resistance arteries, chronic ischemia specifically attenuated the component of relaxation that was insensitive to N G -n i t ro - L-arginine ( L - N O A R G ) and indomethacin. The response was sensitive to high potassium saline solution and therefore, presumably mediated by endothelium-derived hyperpolar izing factor. The opposite was observed in the skeletal muscle resistance arteries where ischemia attenuated the endothelium-dependent relaxation sensitive to L - N O A R G and indomethacin. In this vascular bed, the component sensitive to high potassium saline solution was unaffected by chronic ischemia. Therefore, the mechanisms underlying endothelium-dependent relaxations are altered differentially in the two main vascular beds in the ischemic limb of patients with advanced peripheral vascular disease.
