Abstract
Introduction: Patients with claudication due to peripheral artery disease (PAD) have walking and quality of life (QOL) limitations associated with development of ischemic myopathy. Characteristics of PAD-related ischemic myopathy include myofiber degeneration, mitochondrial dysfunction, and oxidative damage. We hypothesize that revascularization operations improve lower extremity hemodynamics, function, and QOL with improvements in key indicators of PAD-related ischemic myopathy. Methods: Patients undergoing open or endovascular revascularization were evaluated before and 6 months after intervention. QOL was assessed by Short Form-36 (SF-36) and Walking Impairment Questionnaire (WIQ). Walking performance was measured by six-minute walking distance (6MWD) and Gardner maximal Treadmill test (Peak Walking Time - PWT). Calf muscle biomechanics were measured by plantar flexor peak force (PFPF) and power generation (PFPG). Limb hemodynamics were measured with Ankle-Brachial Index (ABI) and myopathy was assessed via gastrocnemius biopsy. Myofibers were evaluated for mitochondrial function via respirometry while slide mounted specimens of the gastrocnemius were analyzed for biomarkers of morphology (myofiber cross-sectional area) and myofiber oxidative damage (carbonyl groups) by quantitative fluorescence microscopy. Results: We recruited 52 patients who underwent 34 open and 18 endovascular revascularizations. Average score improved in 7 of 8 SF-36 (p<0.03) and 4 of 4 WIQ categories (p<0.001). PWT and 6MWD increased 305±75s (111.9%, p<0.001) and 62±17M (21.3%, p<0.001) respectively. PFPF and PFPG increased 9.8±3.1N (17.1%, p=0.001) and 1.6±0.08W/Kg (26.9%, p<0.001) respectively. ABI increased from 0.46±0.03 to 0.87±0.03 (90.4%, p<0.001). Myofiber cross-sectional area increased 458±216 μm 2 (11.1%, p<0.05). Complex I-mediated mitochondrial respiration (normalized to citrate synthase activity) improved 8.1±2.8 (15.4%, p<0.01). Oxidative damage observed as carbonyl groups was reduced 132±60 grayscale units (8.0%, p<0.05). Conclusions: Revascularization operations improved the hemodynamics, QOL and leg function of PAD patients in association with improvement in PAD-related ischemic myopathy.
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