Improvement in systemic endothelial condition following amputation in patients with critical limb ischemia

Aim. Most patients with critical limb ischemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality. Peripheral ischemic tissue produces circulating toxic molecules, which may worsen endothelial function systemically and contribute to the general atherosclerotic process within the body. We looked at whether markers of endothelial function improve after amputation of the ischemic limb, when this potential source of toxins has been removed. Methods. We measured blood levels of vascular endothelial growth factor (VEGF), homocysteine, endothelin-1, vascular cell adhesion molecule-1, E-selectin, thrombomodulin and von Willebrand factor (vWF) in 40 patients with CLI. We also assessed peripheral microvascular function in forearm skin by measuring responses to iontophoresis of acetylcholine and sodium nitroprusside. The measurements were repeated 6 months after amputation. Results. We found abnormally high levels of endothelial products in the patients, and 6 months later VEGF and vWF had both reduced significantly from previous values (by 70% and 40%, respectively; P < 0.01 in both cases). Conclusion. improvements in these two markers after amputation are consistent with the hypothesis that peripheral ischemic tissue has a systemic effect on the vascular endothelium and may contribute to the progression of coronary heart disease in patients with CLI.