scholarly journals Cytokine signature of inflammation mediated by autoreactive Th-cells, in calf muscle of claudicating patients with Fontaine stage II peripheral artery disease

2021 ◽  
Vol 228 ◽  
pp. 94-108
Author(s):  
George P. Casale ◽  
Jonathan R. Thompson ◽  
Lauren C. Carpenter ◽  
Julian Kim ◽  
Timothy J. Lackner ◽  
...  
2020 ◽  
Vol 9 (8) ◽  
pp. 2575
Author(s):  
Constance J. Mietus ◽  
Timothy J. Lackner ◽  
Petros S. Karvelis ◽  
Gregory T. Willcockson ◽  
Christina M. Shields ◽  
...  

Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 μm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree—including the smallest micro-vessels.


Angiology ◽  
2019 ◽  
Vol 70 (8) ◽  
pp. 747-755 ◽  
Author(s):  
Andrew W. Gardner ◽  
Polly S. Montgomery ◽  
Ming Wang ◽  
Chixiang Chen ◽  
Marcos Kuroki ◽  
...  

We determined whether calf muscle oxygen saturation (StO2) and vascular biomarkers of inflammation and oxidative stress were associated with an exercise pressor response during treadmill walking in 179 patients with symptomatic peripheral artery disease (PAD). The exercise pressor response was measured as the change in blood pressure from rest to the end of the first 2-minute treadmill stage (2 mph, 0% grade). There was a wide range in the change in systolic blood pressure (−46 to 50 mm Hg) and in diastolic blood pressure (−23 to 38 mm Hg), with mean increases of 4.3 and 1.4 mm Hg, respectively. In multiple regression analyses, significant predictors of systolic pressure included glucose ( P < .001) and insulin ( P = .039). Significant predictors of diastolic pressure included cultured endothelial cell apoptosis ( P = .019), the percentage drop in exercise calf muscle (StO2; P = .023), high-sensitivity C-reactive protein ( P = .032), and glucose ( P = .033). Higher levels in pro-inflammatory vascular biomarkers, impaired calf muscle StO2 during exercise, and elevated blood glucose were independently associated with greater exercise pressor response in patients with symptomatic PAD. The clinical implication is that exercise and nutritional interventions designed to improve inflammation, microcirculation, and glucose metabolism may also lower blood pressure during exercise in patients with symptomatic PAD.


Angiology ◽  
2012 ◽  
Vol 64 (5) ◽  
pp. 364-370 ◽  
Author(s):  
Aman Khurana ◽  
Julie A. Stoner ◽  
Thomas L. Whitsett ◽  
Suman Rathbun ◽  
Polly S. Montgomery ◽  
...  

2002 ◽  
Vol 64 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Marco Rossi ◽  
Adamasco Cupisti ◽  
Lauretana Perrone ◽  
Serena Mariani ◽  
Gino Santoro

2017 ◽  
Vol 123 (6) ◽  
pp. 1599-1609 ◽  
Author(s):  
Wesley B. Baker ◽  
Zhe Li ◽  
Steven S. Schenkel ◽  
Malavika Chandra ◽  
David R. Busch ◽  
...  

We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS), and frequency-domain near-infrared spectroscopy (FD-NIRS) to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients ( n = 64) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 mo of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at 3 mo in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29% (13%, 50%) and 8% (1%, 12%), respectively [ P < 0.001; median (25th percentile, 75th percentile)]. These improvements across the exercise group population were significantly higher than corresponding changes in the control group ( P < 0.004). Exercise training also increased PWT by 49% (18%, 101%) ( P = 0.01). However, within statistical error, the ABI, resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin\myoglobin desaturation following cessation of maximal exercise were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT. NEW & NOTEWORTHY We report on noninvasive optical measurements of skeletal muscle blood flow and oxygen extraction dynamics before/during/after treadmill exercise in peripheral artery disease patients who experience claudication. The measurements tracked the effects of a 3-mo supervised exercise training protocol and revealed that supervised exercise training improved patient ability to increase microvascular calf muscle blood flow and oxygen extraction during physical activity.


2012 ◽  
Vol 17 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Amy M West ◽  
Justin D Anderson ◽  
Frederick H Epstein ◽  
Craig H Meyer ◽  
Klaus D Hagspiel ◽  
...  

We hypothesized that percutaneous intervention in the affected lower extremity artery would improve calf muscle perfusion and cellular metabolism in patients with claudication and peripheral artery disease (PAD) as measured by magnetic resonance imaging (MRI) and spectroscopy (MRS). Ten patients with symptomatic PAD (mean ± SD: age 57 ± 9 years; ankle–brachial index (ABI) 0.62 ± 0.17; seven males) were studied 2 months before and 10 months after lower extremity percutaneous intervention. Calf muscle phosphocreatine recovery time constant (PCr) in the revascularized leg was measured by 31P MRS immediately after symptom-limited exercise on a 1.5-T scanner. Calf muscle perfusion was measured using first-pass gadolinium-enhanced MRI at peak exercise. A 6-minute walk and treadmill test were performed. The PCr recovery time constant improved significantly following intervention (91 ± 33 s to 52 ± 34 s, p < 0.003). Rest ABI also improved (0.62 ± 0.17 to 0.93 ± 0.25, p < 0.003). There was no difference in MRI-measured tissue perfusion or exercise parameters, although the study was underpowered for these endpoints. In conclusion, in this pilot study, successful large vessel percutaneous intervention in patients with symptomatic claudication, results in improved ABI and calf muscle phosphocreatine recovery kinetics.


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