Abstract 17825: Abnormal Morphology of Skeletal Muscle Myofibers Is Associated With Limb Dysfunction in Peripheral Arterial Disease Patients
Introduction: Peripheral arterial disease (PAD) affects approximately 8.5 million Americans and is characterized by the formation of atherosclerotic plaques that limit blood flow to the legs. Degradation of tissue architecture is characteristic of ischemic muscles in the lower limbs of PAD patients. In this study, we test the hypothesis that morphologic measurements of myofibers in biopsy specimens of PAD patients will differ significantly from the same measurements of myofibers in control biopsies and will correlate with limb dysfunction.
Methods: Gastrocnemius biopsies were collected from forty PAD patients (Fontaine Stage II) and thirty control subjects matched on the basis of age, gender, smoking history and type II diabetes. Biopsy specimens were fixed in methacarn, embedded in paraffin, sectioned and mounted to glass slides. Fluorescence labeling of Myosin Heavy chains (fast and slow twitch) and of the sarcolemma of individual myofibers were used to identify myofibers and to quantify their morphological parameters. Limb function was determined as isometric plantar flexion force measured by the Biodex dynamometer.
Results: Cross-sectional area, major and minor axes, diameter and perimeter of PAD myofibers were decreased (p<0.05) compared to control myofibers, while roundness was increased (p<0.05). Isometric plantar flexion force was correlated with myofiber cross-sectional area (r=0.673, p<0.05), major and minor axes (r=0.764, p<0.01; r= 0.855, p<0.01), diameter (r=0.845, p<0.01) and perimeter (r=0.664, p<0.05).
Conclusions: We conclude that the morphology of myofibers in the gastrocnemius of PAD patients differed from that of control subjects and correlated with limb function. Morphologic changes in gastrocnemius myofibers may serve as a useful biomarker for prognosis and for identification of patients who would benefit from aggressive therapy. Furthermore, measureable changes in myofiber morphology may precede detectable changes in limb function and may serve to identify therapeutic interventions that are effective and should be continued.
- © 2013 by American Heart Association, Inc.