Protocol optimization and physiological specificity of ASL-measured reactive hyperemia in skeletal muscle

Background Evidence suggests that microvascular function may be compromised in Peripheral Arterial Disease (PAD) due to associated endothelial dysfunction. While revascularization is recommended for PAD patients with macrovascular occlusions, a solution for endothelial dysfunction remains unavailable. For a possible endothelium-targeted therapy to be applied, the burden of endothelial dysfunction at different disease stages needs to be characterized. Microvascular function is commonly tested through measurement of reactive hyperemia induced by a short period of ischemia. However, patients with endothelial dysfunction may still demonstrate hyperemia due to build-up of metabolites causing relaxation on their relatively intact vascular smooth muscles. We measured and characterized the reactive hyperemia after various durations of arterial occlusion in the leg, with the goal to reduce the influence of tissue metabolites on detection of endothelial dysfunction.