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dc.contributor.authorCluff, Kim
dc.contributor.authorMiserlis, Dimitrios
dc.contributor.authorNaganathan, Govindarajan Konda
dc.contributor.authorPipinos, Iraklis I.
dc.contributor.authorKoutakis, Panagiotis
dc.contributor.authorSamal, Ashok
dc.contributor.authorMcComb, Rodney D.
dc.contributor.authorSubbiah, Jeyamkondan
dc.contributor.authorCasale, George P.
dc.identifier.citationCluff, Kim; Miserlis, Dimitrios; Naganathan, Govindarajan Konda; Pipinos, Iraklis I.; Koutakis, Panagiotis; Samal, Ashok; McComb, Rodney D.; Subbiah, Jeyamkondan; Casale, George P.. 2013. Morphometric analysis of gastrocnemius muscle biopsies from patients with peripheral arterial disease: objective grading of muscle degeneration. Am J Physiol Regul Integr Comp Physiol. 2013 Aug;v.305:no.3:pp.R291-R299en_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractPeripheral arterial disease (PAD), which affects ∼10 million Americans, is characterized by atherosclerosis of the noncoronary arteries. PAD produces a progressive accumulation of ischemic injury to the legs, manifested as a gradual degradation of gastrocnemius histology. In this study, we evaluated the hypothesis that quantitative morphological parameters of gastrocnemius myofibers change in a consistent manner during the progression of PAD, provide an objective grading of muscle degeneration in the ischemic limb, and correlate to a clinical stage of PAD. Biopsies were collected with a Bergström needle from PAD patients with claudication (n = 18) and critical limb ischemia (CLI; n = 19) and control patients (n = 19). Myofiber sarcolemmas and myosin heavy chains were labeled for fluorescence detection and quantitative analysis of morphometric variables, including area, roundness, perimeter, equivalent diameter, major and minor axes, solidity, and fiber density. The muscle specimens were separated into training and validation data sets for development of a discriminant model for categorizing muscle samples on the basis of disease severity. The parameters for this model included standard deviation of roundness, standard deviation of solidity of myofibers, and fiber density. For the validation data set, the discriminant model accurately identified control (80.0% accuracy), claudicating (77.7% accuracy), and CLI (88.8% accuracy) patients, with an overall classification accuracy of 82.1%. Myofiber morphometry provided a discriminant model that establishes a correlation between PAD progression and advancing muscle degeneration. This model effectively separated PAD and control patients and provided a grading of muscle degeneration within clinical stages of PAD.en_US
dc.description.sponsorshipStrategic Research Grant from the Agriculture Research Division of the University of Nebraska-Lincoln, a grant from the NIH (5R01AG034995-01), the Charles and Mary Heider Fund for Excellence in Vascular Surgery, and the Alexander S. Onassis Public Benefit Foundation.en_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.ispartofseriesAm J Physiol Regul Integr Comp Physiol;v.305:no.3
dc.subjectMyofiber morphologyen_US
dc.subjectFluorescence microscopyen_US
dc.subjectLinear discriminant analysisen_US
dc.titleMorphometric analysis of gastrocnemius muscle biopsies from patients with peripheral arterial disease: objective grading of muscle degenerationen_US
dc.description.versionPeer reviewed
dc.rights.holderCopyright © 2012, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology

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