Optical probing of gastrocnemius in patients with peripheral artery disease characterizes myopathic biochemical alterations and correlates with stage of disease

Becker, Ryan A.; Cluff, Kim; Duraisamy, Nithyanandhi; Mehraein, Hootan; Farhoud, Hussam; Collins, Tracie C.; Casale, George P.; Pipinos, Iraklis I.; Subbiah, Jeyamkondan

doi:10.14814/phy2.13161

Cited by 6 publications

(2 citation statements)

References 76 publications

(149 reference statements)

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“…2,3 Indeed, 34% of patients with CLI undergo major limb amputation within 12 months. 4 The lack of improvement in symptoms in patients despite revascularisation is due in part to a myopathy [5][6][7][8] within the ischemic muscle. The pathophysiology of skeletal muscle damage following ischemia is unclear, but a number of detrimental physiological and biochemical changes have been identified.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

et al. 2019

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Critical limb ischemia (CLI) is associated with skeletal muscle damage. However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. Thus, manipulating the TLR pathway locally may be of potential therapeutic benefit.

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Section: Introductionmentioning

confidence: 99%

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

et al. 2019

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“…The pathophysiology of PAD is complex and involves changes occurring on both physical and biochemical levels such as reduced blood flow, altered metabolic processes, skeletal muscle degeneration, and oxidative damage (7–11). The Ankle brachial index (ABI) is a simple and noninvasive test physicians use to diagnose PAD, and is performed by determining the ratio of systolic blood pressure in the ankle to that in the arm.…”

Section: Introductionmentioning

confidence: 99%

Analysis of ischemic muscle in patients with peripheral artery disease using X-ray spectroscopy

Becker

Cluff

Duraisamy

et al. 2017

Journal of Surgical Research

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Background Peripheral artery disease (PAD) is a vascular disease caused by atherosclerosis resulting in decreased blood flow to the lower extremities. The ankle brachial index (ABI) is a standard PAD diagnostic test, but only identifies reduced blood flow based on blood pressure differences. The early signs of PAD manifest themselves not only clinically, but also at an elemental and biochemical level. However, the biochemical and elemental alterations to PAD muscle are not well understood. The objective of this study was to compare fundamental changes in intracellular elemental compositions between control, claudicating, and critical limb ischemia muscle tissue. Materials and methods Gastrocnemius biopsies from three subjects including one control (ABI≥0.9), one claudicating (0.4≤ABI<0.9) and one critical limb ischemia patient (ABI<0.4) were evaluated using a scanning electron microscope and energy dispersive X-ray spectroscopy to quantify differences in elemental compositions. Spectra were collected for 5 myofibers per specimen. An analysis of variance was performed to identify significant differences in muscle elemental compositions. Results This study revealed that intracellular magnesium and calcium were lower in PAD compared to control myofibers while sulfur was higher. Magnesium and calcium are antagonistic, meaning, if magnesium concentrations go down calcium concentrations should go up. However, our findings do not support this antagonism in PAD. Our analysis found decreases in sodium and potassium, in PAD myofibers. Conclusions These findings may provide insight into the pathologic mechanisms that may operate in ischemic muscle and aid in the development of specialized preventive and rehabilitative treatment plans for PAD patients.

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Gait variability is affected more by peripheral artery disease than by vascular occlusion

Rahman

Pipinos

Johanning

et al. 2020

Preprint

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Background Patients with peripheral artery disease (PAD) have altered gait variability from the first step they take, well before the onset of claudication pain. The mechanisms underlying these gait alterations are poorly understood. Aims This study sought to isolate the effect of reduced blood flow on gait variability by comparing healthy older controls and patients with PAD. We also determined the diagnostic value of gait variability parameters to identify the presence of PAD. Methods Thirty healthy older controls and thirty patients with PAD walked on a treadmill at their self-selected speed in rested (normal walking for controls; pain free for PAD) and reduced blood flow (post vascular occlusion with thigh tourniquet for controls; pain for PAD) conditions. Gait variability was assessed using the largest Lyapunov exponent, approximate entropy, standard deviation, and coefficient of variation of ankle, knee, and hip joints range of motion. Receiver operating characteristics curve analyses of the rested condition were performed to determine the optimal cut-off values for separating individuals with PAD from those without PAD. Results and Discussion Patients with PAD have increased amount of variability for knee and hip ranges of motion compared with healthy older group. Comparing for conditions, reduced blood flow demonstrated increased amount of variability compared with rested blood flow. Significant interactions between group and condition occurred at the ankle for Lyapunov exponent, approximate entropy, and coefficient of variation. A combination of gait variability parameters correctly identifies PAD disease 70% of the time or more. Conclusions Gait variability is affected both by PAD and by the mechanical induction of reduced blood flow.

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Optical probing of gastrocnemius in patients with peripheral artery disease characterizes myopathic biochemical alterations and correlates with stage of disease

Cited by 6 publications

References 76 publications

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

Analysis of ischemic muscle in patients with peripheral artery disease using X-ray spectroscopy

Gait variability is affected more by peripheral artery disease than by vascular occlusion

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