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VASA. Zeitschrift Fur Gefasskrankheiten Nov 2007In recent years the importance of circulating bone marrow-derived cells in angiogenesis and collateral growth has been demonstrated in peripheral artery disease (PAD)... (Review)
Review
In recent years the importance of circulating bone marrow-derived cells in angiogenesis and collateral growth has been demonstrated in peripheral artery disease (PAD) and other ischaemic diseases. Although the mechanisms by which these cells exert their angiogenetic/arteriogenetic effects are not completely understood, improving the accumulation of bone marrow-derived cells at the site of vascular growth using cytokines has become one aim in some of the regenerative therapies. Interestingly recent data indicate that in addition to effects attributed to such accumulated cells there are also direct effects of cytokines used via their receptors. Several investigations in animal hind limb models of ischaemia have demonstrated the beneficial effect of bone marrow mobilisation using colony-stimulating factors (CSF) on collateral growth and perfusion recovery. Clinical studies in PAD patients, however are still rare and led to inconsistent data, in part due to different application protocols, choice of cytokine and low patient numbers with strong placebo effects. Moreover; the aetiology of the disease in humans differs markedly from the artificial occlusion of the femoral artery in a mostly healthy animal in the preclinical setting. Another approach to enhance arteriogenesis, which has been successful in animal models of hind limb ischaemia, is the local injection of the monocyte chemoattractant protein 1 (MCP-1). This treatment stimulated the invasion of monocytes leading to improved collateral growth and restoration of limb perfusion. Recent reports from animal experiments, in which both treatment strategies were combined (i.e. bone marrow mobilisation and enhancement of cell migration to the site of vascular growth), have shown strong synergistic effects, pointing at the importance to orchestrate the different processes involved in vascular repair in order to achieve maximal therapeutic effects.
Topics: Animals; Arterial Occlusive Diseases; Bone Marrow Cells; Chemokine CCL2; Cytokines; Disease Models, Animal; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hindlimb; Humans; Ischemia; Leg; Neovascularization, Physiologic
PubMed: 18357917
DOI: 10.1024/0301-1526.36.4.253 -
Anaesthesia May 1998
Review
Topics: Acute Disease; Compartment Syndromes; Crush Syndrome; Humans; Hyperbaric Oxygenation; Ischemia; Wounds and Injuries
PubMed: 9659073
DOI: 10.1111/j.1365-2044.1998.tb15161.x -
PloS One 2020Antiplatelet therapy following peripheral arterial endovascular intervention lacks high quality evidence to guide practice. The aim of this study was to assess the... (Comparative Study)
Comparative Study
OBJECTIVES
Antiplatelet therapy following peripheral arterial endovascular intervention lacks high quality evidence to guide practice. The aim of this study was to assess the effect of three months of dual antiplatelet therapy on amputation-free survival following peripheral arterial endovascular intervention in patients with chronic limb threatening ischemia.
METHODS
A retrospective review of symptomatic patients undergoing primary peripheral arterial endovascular intervention over a seven-year period was performed. The primary outcome measure was amputation-free survival. A sample size calculation based on previous cohort studies suggested that 629 limbs would be required to show a difference between single and dual therapy. Kaplan-Meier estimates and multivariate logistic regression analysis of recorded baseline characteristics was performed to determine predictors of amputation-free survival. Dual antiplatelet therapy was routinely given for 3 months.
RESULTS
754 limbs were treated with primary angioplasty and/or stenting over a 7-year period, 508 of these for chronic limb threatening ischemia. There was no difference in unadjusted amputation-free survival between patients with chronic limb threatening ischaemia taking single vs. dual antiplatelet therapy (69% vs. 74% respectively Log rank Chi2 = 0.1, p = .72). After adjusting for confounders, at 1 year there was also no significant difference in amputation-free survival between patients taking single vs. dual antiplatelet therapy [OR 0.8, 95% CI 0.5-1.2, p = .3]. There was no difference in rates of major bleeding between single and dual antiplatelet therapy.
CONCLUSIONS
There was no clear evidence of reduced amputation-free survival in patients with chronic limb threatening ischemia undergoing peripheral arterial endovascular intervention being treated with dual antiplatelet therapy for 3 months. This is at odds with other retrospective case series and highlights the limitations in basing clinical practice on such data. There is a need for an adequately powered, independent randomised trial to definitively answer the question.
Topics: Aged; Cohort Studies; Endovascular Procedures; Female; Humans; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Survival Analysis
PubMed: 32525925
DOI: 10.1371/journal.pone.0234271 -
European Heart Journal May 2022
Topics: Chronic Limb-Threatening Ischemia; Cohort Studies; Humans; Ischemia; Peripheral Arterial Disease; Treatment Outcome
PubMed: 35137028
DOI: 10.1093/eurheartj/ehac047 -
VASA. Zeitschrift Fur Gefasskrankheiten Nov 2007Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis that is associated with a significant limitation in limb function due to... (Review)
Review
Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis that is associated with a significant limitation in limb function due to ischaemia and high risk of cardiovascular mortality. The lower limb manifestations of PAD principally fall into the categories of chronic stable claudication, critical leg ischaemia, and, rarely, acute limb ischaemia. Lower limb ischaemia induced by PAD is a major health problem. In the absence of effective pharmacological, interventional or surgical treatment, amputation is undertaken at the end-stage as a solution to unbearable symptoms. The concept of "therapeutic angiogenesis" has become widely accepted during the past few years. Bone marrow consists of multiple cell populations, including endothelial progenitor cells, which have been shown to differentiate into endothelial cells and release several angiogenic factors and thereby enhance neovascularisation in animal models of hind limb ischaemia. The promising results from various preclinical studies provide the basis for clinical trials using bone marrow-derived cells or non-bone marrow cells, like cells from the peripheral blood or other tissues. However, the mechanisms by which these cells exert their positive effects are poorly understood until now. This review summarises the data from experimental and clinical studies related to peripheral arterial disease and cellular therapy.
Topics: Angiogenesis Inducing Agents; Animals; Arterial Occlusive Diseases; Bone Marrow Transplantation; Cell Differentiation; Clinical Trials as Topic; Disease Models, Animal; Endothelial Cells; Hindlimb; Humans; Ischemia; Leg; Mice; Neovascularization, Physiologic; Rabbits; Rats
PubMed: 18357916
DOI: 10.1024/0301-1526.36.4.241 -
European Journal of Vascular and... Feb 2020
Topics: Humans; Ischemia; Peripheral Vascular Diseases; Vascular Surgical Procedures
PubMed: 32029196
DOI: 10.1016/j.ejvs.2020.01.001 -
European Journal of Vascular and... Oct 2009Endothelial progenitor cells (EPC) are a subpopulation of bone-marrow mononuclear cells that are capable of generating new blood vessels in areas of ischaemia or... (Review)
Review
BACKGROUND
Endothelial progenitor cells (EPC) are a subpopulation of bone-marrow mononuclear cells that are capable of generating new blood vessels in areas of ischaemia or infarction. This review examines the regenerative potential of EPC to ameliorate peripheral ischaemia.
METHODS
An online search was done using OVID Medline Search, PubMed, and Cochrane Review Database, for all reviews and original articles in English concerning progenitor or bone-marrow mononuclear cells.
RESULTS AND CONCLUSION
There are many controversies in EPC research, especially in the areas of identification, characterization, and therapeutic use. Both animal and human studies have shown benefits from using EPC to combat peripheral arterial and cerebrovascular disease. To bring EPC into wider clinical use, larger controlled clinical trials and better methods of augmenting EPC function and lifespan are required. Until then EPC should be used under robust trial conditions with ethical approval.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cell Differentiation; Cell Proliferation; Cell Survival; Cerebrovascular Disorders; Endothelial Cells; Extremities; Humans; Ischemia; Myocardial Ischemia; Neovascularization, Physiologic; Peripheral Vascular Diseases; Risk Factors; Stem Cell Transplantation; Treatment Outcome
PubMed: 19560945
DOI: 10.1016/j.ejvs.2009.05.019 -
European Journal of Vascular and... Aug 2023
Topics: Humans; Chronic Limb-Threatening Ischemia; Vascular Surgical Procedures; Limb Salvage; Ischemia; Treatment Outcome; Retrospective Studies; Peripheral Arterial Disease; Risk Factors
PubMed: 37187286
DOI: 10.1016/j.ejvs.2023.05.010 -
European Journal of Vascular and... Jun 2000
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European Journal of Vascular and... Dec 2011Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and... (Review)
Review
Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade.
Topics: Amputation, Surgical; Debridement; Diabetic Foot; Diabetic Neuropathies; Diagnostic Imaging; Humans; Ischemia; Peripheral Vascular Diseases; Practice Guidelines as Topic; Surgical Flaps; Vascular Surgical Procedures
PubMed: 22172474
DOI: 10.1016/S1078-5884(11)60012-9