Abstract
Peripheral artery disease (PAD) is a condition caused by atherosclerotic blockages in the arteries supplying the lower limbs and is characterized by ischemia of the leg, progressive myopathy, and increased risk of limb loss. The affected leg muscles undergo significant changes of their biochemistry and metabolism including variations in the levels of many key proteins, lipids, and nucleotides. The mechanisms behind these changes are poorly understood. The objective of this study was to correlate the severity of the PAD disease stage and associated hemodynamic limitation (determined by the ankle brachial index, ABI) in the legs of the patients with alterations in the biochemistry of chronically ischemic leg muscle as determined by ATR‐Fourier transform infrared micro‐spectroscopy. Muscle (gastrocnemius) biopsies were collected from 13 subjects including four control patients (ABI≥0.9), five claudicating patients (0.4 ≤ ABI<0.9), and four critical limb ischemia (CLI) patients (ABI<0.4). Slide mounted specimens were analyzed by ATR‐Fourier transform infrared micro‐spectroscopy. An analysis of variance and a partial least squares regression model were used to identify significant differences in spectral peaks and correlate them with the ABI. The spectra revealed significant differences (P < 0.05) across control, claudicating, and CLI patients in the fingerprint and functional group regions. Infrared microspectroscopic probing of ischemic muscle biopsies demonstrates that PAD produces significant and unique changes to muscle biochemistry in comparison to control specimens. These distinctive biochemical profiles correlate with disease progression and may provide insight and direction for new targets in the diagnosis and therapy of muscle degeneration in PAD.
Highlights
Peripheral artery disease (PAD) is a consequence of reduced blood flow caused by atherosclerotic plaque buildup, (Schirmang et al 2009) causing stenosis and obstruction in the arteries supplying the lower limbs
We demonstrated that Attenuated total reflectance (ATR)-Fourier Transform Infrared (FTIR) microspectroscopy can perform detailed and precise measurements of the biochemical changes that occur in the chronically ischemic muscles of PAD patients
This is the first study to produce ATR-FTIR profiles of normal and diseased skeletal muscle and our data demonstrate that the skeletal muscle is very sensitive to chronic ischemia and undergoes biochemical changes that correspond to the degree of hemodynamic compromise and the clinical severity of PAD
Summary
Peripheral artery disease (PAD) is a consequence of reduced blood flow caused by atherosclerotic plaque buildup, (Schirmang et al 2009) causing stenosis and obstruction in the arteries supplying the lower limbs If the disease continues to progress, blood flow to the extremities continues to decrease, causing critical limb ischemia (CLI), a condition characterized by chronic ischemic pain at rest and tissue loss (nonhealing ulcers or gangrene). At this stage of the disease, the prognosis of the limb is poor, with half of patients presenting with CLI requiring limb amputation within 1 year from their presentation (Feinglass et al 1999; Norgren et al 2007; Ziegler-Graham et al 2008). Metabolic demands of the ischemic tissue, the location of the affected artery, and the degree of the myopathy in the leg muscles are all key factors that influence the severity of PAD symptoms (Pipinos et al 2007, 2008; Hills et al 2009)
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