Progressive Deterioration in Skeletal Muscle Microcirculatory and Mitochondrial Function in Patients with Claudication and Critical Limb Ischemia
Presenter Type
UNO Graduate Student (Doctoral)
Major/Field of Study
Health and Kinesiology
Other
Biomechanics and Kinesiology
Advisor Information
Dr.
Location
MBSC302 - G (Doctoral)
Presentation Type
Oral Presentation
Start Date
24-3-2023 9:00 AM
End Date
24-3-2023 10:15 AM
Abstract
Introduction: Peripheral artery disease (PAD) is an atherosclerotic disease that impairs blood flow to the lower extremities. Early-stage patients often present with intermittent claudication (leg pain during walking, CLD), but as the disease progresses, patients can experience pain at rest and tissue death (critical limb ischemia, CLI). We recently reported that patients with claudication present with skeletal muscle microvascular dysfunction. However, it is unknown if microvascular dysfunction continues with disease progression. Objective: Compare a direct investigation of skeletal muscle microcirculation and mitochondrial respiration in patients with claudication and patients with CLI. Hypothesis: We hypothesize that (1) CLI will have greater attenuation in microcirculatory endothelial-dependent and endothelial-independent vasodilatory function (smooth muscle function) than CLD and (2) impairments in skeletal muscle microcirculatory vasodilatory function will contribute to attenuated mitochondrial respiratory function in CLD and CLI. Methods: Medial gastrocnemius muscles were harvested from CLD patients (n=5), CLI (n=6), and age-matched controls (n 6) by muscle biopsies. Arterioles were isolated to assess endothelium-dependent and independent vasodilatory responses to flow (30 L·min-1), acetylcholine (ACh), and sodium nitroprusside (SNP). Skeletal muscle mitochondrial respiration was determined by high-resolution respirometry. Results: Endothelium-dependent vasodilation was attenuated (P0.05). Complex I+II state 3 mitochondrial respiration was blunted in both CLD and CLI compared to CON (P
Scheduling
9:15-10:30 a.m.
Progressive Deterioration in Skeletal Muscle Microcirculatory and Mitochondrial Function in Patients with Claudication and Critical Limb Ischemia
MBSC302 - G (Doctoral)
Introduction: Peripheral artery disease (PAD) is an atherosclerotic disease that impairs blood flow to the lower extremities. Early-stage patients often present with intermittent claudication (leg pain during walking, CLD), but as the disease progresses, patients can experience pain at rest and tissue death (critical limb ischemia, CLI). We recently reported that patients with claudication present with skeletal muscle microvascular dysfunction. However, it is unknown if microvascular dysfunction continues with disease progression. Objective: Compare a direct investigation of skeletal muscle microcirculation and mitochondrial respiration in patients with claudication and patients with CLI. Hypothesis: We hypothesize that (1) CLI will have greater attenuation in microcirculatory endothelial-dependent and endothelial-independent vasodilatory function (smooth muscle function) than CLD and (2) impairments in skeletal muscle microcirculatory vasodilatory function will contribute to attenuated mitochondrial respiratory function in CLD and CLI. Methods: Medial gastrocnemius muscles were harvested from CLD patients (n=5), CLI (n=6), and age-matched controls (n 6) by muscle biopsies. Arterioles were isolated to assess endothelium-dependent and independent vasodilatory responses to flow (30 L·min-1), acetylcholine (ACh), and sodium nitroprusside (SNP). Skeletal muscle mitochondrial respiration was determined by high-resolution respirometry. Results: Endothelium-dependent vasodilation was attenuated (P0.05). Complex I+II state 3 mitochondrial respiration was blunted in both CLD and CLI compared to CON (P