scholarly journals Development of an Exercise Training Protocol to Investigate Arteriogenesis in a Murine Model of Peripheral Artery Disease

2019 ◽  
Vol 20 (16) ◽  
pp. 3956 ◽  
Author(s):  
Ayko Bresler ◽  
Johanna Vogel ◽  
Daniel Niederer ◽  
Daphne Gray ◽  
Thomas Schmitz-Rixen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Suitable Model ◽  
Peripheral Artery ◽  
Running Wheel ◽  
Limb Perfusion ◽  
Collateral Growth ◽  
Artery Disease ◽  
Set Up ◽  
Exercise Induced ◽  
And Control

Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to develop an animal model to stimulate collateral growth in mice through exercise. The training intensity assessment consisted of comparing two different training regimens in C57BL/6 mice, a treadmill implementing forced exercise and a free-to-access voluntary running wheel. The mice in the latter group covered a much greater distance than the former pre- and postoperatively. C57BL/6 mice and hypercholesterolemic ApoE-deficient (ApoE−/−) mice were subjected to FAL and had either access to a running wheel or were kept in motion-restricting cages (control) and hind limb perfusion was measured pre- and postoperatively at various times. Perfusion recovery in C57BL/6 mice was similar between the groups. In contrast, ApoE−/− mice showed significant differences between training and control 7 d postoperatively with a significant increase in pericollateral macrophages while the collateral diameter did not differ between training and control groups 21 d after surgery. ApoE−/− mice with running wheel training is a suitable model to simulate exercise induced collateral growth in PAD. This experimental set-up may provide a model for investigating molecular training effects.

scholarly journals High prevalence of exercise-induced ischemia in the asymptomatic limb of patients with apparently strictly unilateral symptoms and unilateral peripheral artery disease

2019 ◽  
Vol 13 ◽  
pp. 175394471881906 ◽  
Author(s):  
Samir Henni ◽  
Pascal Bauer ◽  
Tanguy Le Meliner ◽  
Jeanne Hersant ◽  
Xavier Papon ◽  
...  
Keyword(s):  
Pressure Drop ◽  
Peripheral Artery Disease ◽  
Systolic Pressure ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Pressure Index ◽  
High Prevalence ◽  
Artery Disease ◽  
Exercise Induced ◽  
Brachial Systolic Pressure

Background: The prevalence of exercise-induced ischemia in the asymptomatic limb of patients with unilateral claudication based on history and treadmill evaluation, and with unilateral ipsilateral peripheral artery disease (i.e ankle-to-brachial systolic pressure index <0.90) is unknown. Methods: We detected exercise-induced ischemia in the asymptomatic limb of patients with apparently unilateral claudication. Among 6059 exercise-oximetry tests performed in 3407 nondiabetic and 961 diabetic patients. We estimated the intensity of ischemia in the both limb (buttocks and calves) using the lowest minimum value of the decrease from rest of oxygen pressure (DROP; limb changes minus chest changes from rest), with significant ischemia defined as DROP lower than −15 mmHg. Results: We found 152 tests performed in 142 nondiabetic patients and 40 tests performed in 38 diabetic patients. The asymptomatic limb showed significant ischemia in 46.7% and 37.5% of the tests. Strictly unilateral exercise-induced claudication with apparently unilateral peripheral artery disease was rare (<4% of all tests). However, among these highly selected tests, significant ischemia was found in the asymptomatic limb in more than one-third of cases. Conclusion: The asymptomatic limb of patients with peripheral artery disease should not be considered a normal limb.

scholarly journals Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease

2018 ◽  
Author(s):  
Igor Giarretta ◽  
Ilaria Gatto ◽  
Margherita Marcantoni ◽  
Giulia Lupi ◽  
Diego Tonello ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Sonic Hedgehog ◽  
Crucial Role ◽  
Experimental Studies ◽  
Clinical Implications ◽  
Peripheral Artery ◽  
Circulating Microparticles ◽  
Artery Disease ◽  
And Control

Sonic Hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh+ MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. In this study, the plasma&nbsp; number of Shh+ MPs in patients with peripheral artery disease (PAD) and control subjects without PAD. We found significantly higher number of Shh+ MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs &ndash; produced either by endothelial cells, platelets, leukocytes, and erythrocytes &ndash; was not different between PAD patients and controls. Interestingly, the concentration of Shh protein unbound to MPs &ndash; which was measured in MP-depleted plasma &ndash; was not different between subjects with PAD and controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel insights on the mechanisms through which the Shh signaling is reactivated during ischemia in humans, with potentially important fundamental and clinical implications.

scholarly journals Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease

2018 ◽  
Vol 19 (12) ◽  
pp. 3954 ◽  
Author(s):  
Igor Giarretta ◽  
Ilaria Gatto ◽  
Margherita Marcantoni ◽  
Giulia Lupi ◽  
Diego Tonello ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Artery Disease ◽  
Sonic Hedgehog ◽  
Experimental Studies ◽  
Clinical Implications ◽  
Peripheral Artery ◽  
Circulating Microparticles ◽  
Artery Disease ◽  
Collateral Vessels ◽  
And Control

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.

Abstract 115: Microvascular Response to Ramipril in Peripheral Artery Disease

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Constance J Mietus ◽  
Peter Karvelis ◽  
Timothy Lackner ◽  
Hernan Hernandez ◽  
Holly DeSpiegelaere ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Wall Thickness ◽  
Walking Distance ◽  
Lumen Diameter ◽  
Peripheral Artery ◽  
Vascular Walls ◽  
Organ Systems ◽  
Walking Performance ◽  
Artery Disease ◽  
And Control

Background: The myopathy of Peripheral Artery Disease (PAD), a consequence of ischemia caused by atherosclerotic plaques in arteries supplying the legs, is characterized by myofiber degeneration and fibrosis of the vascular walls and extramyofiber matrix. In association with fibrosis we have found a robust expression of the profibrotic cytokine TGFβ1 in vascular smooth muscle cells. Additionally, we have observed microvascular endothelial “swelling” in PAD muscle. Published data indicate that inhibitors of the angiotensin system reduce fibrosis in multiple organ systems and improve walking performance, in diverse patient populations. We hypothesize that “swelling” of microvasculature endothelial cells represents abnormal accumulation of basement membrane Collagen Type IV (Col-IV) and that treatment with Ramipril will improve the microvasculature. Methods and Results: Gastrocnemius biopsies of PAD patients at Fontaine Stage II (N=5) before and after six months of Ramipril intervention and control patients (N=4) were labeled with an antibody specific for Col-IV. Images were acquired with an automated wide-field microscope and then processed with Image Pro Plus® and AutoQuant® deconvolution software. We used Col IV label to measure wall thickness and lumen diameter of 230 to 360 microvessels per patient, with a custom MatLab program based on the Expectation Maximization algorithm coupled with a Gaussian Mixture Model. Microvessel wall thickness was significantly greater (p < 0.04) in PAD patients before (1.54 ± 0.04 μ) and after (1.61 ± 0.06 μ) Ramipril treatment compared to control (1.42 ± 0.02). Lumen diameter was significantly greater (p < 0.02) in Post-Ramipril (3.49 ± 0.04 μ) compared to Pre-Ramipril (3.18 ± 0.08 μ) and control (3.00 ± 0.11 μ) patients. Conclusions: The increase of microvessel lumen diameter with Ramipril treatment is expected to increase microvascular perfusion and thereby improve walking distance. Our study will be expanded to increase cohort size and evaluate the association of microvascular measurements with microperfusion determined by Contrast Enhanced Ultrasonography and with walking performance.

scholarly journals Exercise versus vasodilator stress limb perfusion imaging for the assessment of peripheral artery disease

2017 ◽  
Vol 34 (8) ◽  
pp. 1187-1194 ◽  
Author(s):  
Brian P. Davidson ◽  
J. Todd Belcik ◽  
Gregory Landry ◽  
Joel Linden ◽  
Jonathan R. Lindner
Keyword(s):  
Peripheral Artery Disease ◽  
Perfusion Imaging ◽  
Vasodilator Stress ◽  
Peripheral Artery ◽  
Limb Perfusion ◽  
Artery Disease

Acute Effect of Exercise-Induced Leg Ischemia on Cutaneous Vasoreactivity in Patients with Stage II Peripheral Artery Disease

2002 ◽  
Vol 64 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Marco Rossi ◽  
Adamasco Cupisti ◽  
Lauretana Perrone ◽  
Serena Mariani ◽  
Gino Santoro
Keyword(s):  
Peripheral Artery Disease ◽  
Acute Effect ◽  
Stage Ii ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Exercise Induced ◽  
Leg Ischemia

scholarly journals Prevalence and Predictors of Lower Extremity Peripheral Artery Disease among Adults with Type 2 Diabetes Mellitus Attending a Tertiary Hospital in Owerri, Nigeria

2019 ◽  
pp. 1-11
Author(s):  
Patrick Chinedu Obi ◽  
Anthony Chinedum Anyanwu ◽  
Chidimma Brenda Nwatu ◽  
Chinonso Ekwueme ◽  
Adaure Mbaike ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Dorsalis Pedis Artery ◽  
Artery Disease ◽  
And Control

Background: Lower extremity peripheral artery disease [LEAD] is common among patients with Diabetes mellitus (DM) and is under-diagnosed and under-treated.  Early diagnosis and treatment will prevent associated cardiovascular events, minimize long term disability and improve quality of life. There is paucity of data on LEAD in Owerri and Southeastern Nigeria in general. Study Objectives: To determine the prevalence and predictors of LEAD among adults with type 2 diabetes mellitus (T2DM). Study Design: Cross-sectional analytical. Study Site: Endocrinology Clinic, Federal Medical Centre, Owerri, Nigeria. Methodology: Two hundred and seventy (270) T2DM patients and 135 non-diabetic controls were recruited consecutively between January and June, 2016. Questionnaires  were  used  to  collect  relevant  information,  followed  by  focused  physical examination and anthropometry. A portable Ankle Brachial Index (ABI) kit was used for measurement of ABI and participants with values < 0.9 were diagnosed as having LEAD. For participants with ABI ≥ 1.3, a toe pressure kit was used to measure their toe systolic pressure and those with toe brachial index (TBI) ≤ 0.7 were diagnosed as having LEAD. Fasting blood samples were also collected for assessment of glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and lipid profile. Data analysis was performed with SPSS version 22 and p-value < 0.05 was considered significant. Results: The mean ages of the T2DM and control participants were 59.8 ± 10.7 and 59.6 ± 12.3 years respectively (P = 0.89) while their mean ABIs were 0.97 ± 0.18 and 0.99 ± 0.16 respectively    (P = 0.26). The  prevalence  of  LEAD  was  31.1%  and  27.4%  among T2DM  and  control  participants respectively (P = 0.44) while among the T2DM participants that had LEAD, 57 (67.8%), 26 (31.0%) and 1 (1.2%) had mild, moderate and severe LEAD respectively. The only predictor of LEAD among T2DM participants was absent/reduced dorsalis pedis artery pulsation (AOR = 3.57, CI = 1.13 – 11.29, P = 0.03). Conclusions and Recommendations: There is a high prevalence of LEAD among adults with T2DM but this is not significantly higher than the prevalence among non-diabetic individuals. Regular screening of T2DM patients for LEAD should be encouraged. There is also need for regular palpation of dorsalis pedis artery among adults with T2DM to identify those with absent or reduced pulsation which may be an indication of the presence of LEAD.

scholarly journals Muscle strength and control characteristics are altered by peripheral artery disease

2017 ◽  
Vol 66 (1) ◽  
pp. 178-186.e12 ◽  
Author(s):  
Molly N. Schieber ◽  
Ryan M. Hasenkamp ◽  
Iraklis I. Pipinos ◽  
Jason M. Johanning ◽  
Nicholas Stergiou ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Artery Disease ◽  
And Control

scholarly journals Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association

Circulation ◽  
2019 ◽  
Vol 140 (12) ◽  
Author(s):  
Sanjay Misra ◽  
Mehdi H. Shishehbor ◽  
Edwin A. Takahashi ◽  
Herbert D. Aronow ◽  
Luke P. Brewster ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Critical Limb Ischemia ◽  
Ankle Brachial Index ◽  
Limb Ischemia ◽  
The United States ◽  
Peripheral Artery ◽  
Limb Perfusion ◽  
Scientific Statement ◽  
Artery Disease ◽  
White Patients

There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed.

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