Management of Peripheral Arterial Disease

Abstract

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors such as cessation of cigarette smoking and control of dyslipidemia, hypertension, and diabetes should be treated. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, and angiotensin-converting enzyme inhibitors should be given to all persons with PAD. beta-Blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol improve exercise time until intermittent claudication. Indications for lower-extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations diminish the benefit of limb salvage.

Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide–mediated vascular smooth muscle relaxation

“…Treatments to address these factors, including hyperbaric oxygen, intravenous thrombolytics, anti-inflammatory agents, and local application of angiogenesis promoters, have been developed but have yielded only limited success. [6][7][8][9][10] Nitric oxide (NO) is a key signaling molecule in ischemia. NO stimulates vascular smooth muscle cell (VSMC) relaxation to increase blood flow and tissue perfusion.…”

Long-term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease

“…Each year, more than 100 000 individuals undergo lower limb amputation because of PADs. 1 An effective clinical treatment for critical limb ischemia is revascularization of affected limbs, which occurs as a result of vasculogenesis and angiogenesis. Vasculogenesis requires the novel recruitment of exogenous stem cell progenitors, whereas angiogenesis involves the quiescent endothelial cell progenitors of the pre-existing vessels.…”

Autologous Bone Marrow Cell Therapy and Metabolic Intervention in Ischemia-Induced Angiogenesis in the Diabetic Mouse Hindlimb

“…1 The management of patients with PAD consists of life-style modifications and pharmacotherapy addressing the risk factors to minimize disease progression and mortality from cardiovascular events, but may necessitate symptomatic invasive treatments of surgical or endovascular revascularization. 1 Unfortunately, about 30% of patients with critical limb ischemia cannot be treated by any of these methods and the only option for them is often amputation, especially in the presence of diabetes. 1,2 Thus, there is a great need for alternative treatment strategies to stimulate collateral artery growth.…”

“…1 Unfortunately, about 30% of patients with critical limb ischemia cannot be treated by any of these methods and the only option for them is often amputation, especially in the presence of diabetes. 1,2 Thus, there is a great need for alternative treatment strategies to stimulate collateral artery growth. Vasculogenesis requires novel recruitment of nonresident stem cell progenitors, whereas angiogenesis involves the quiescent endothelial cell progenitors of the preexisting vessels.…”

“…10 However, to date, the impact of concurrent diabetes during experimental ischemic hindlimb has been poorly investigated, 27,28 despite the fact that the majority of patients with PAD has also elevated levels of blood glucose. 1,2 Therefore, in the present study, we investigated the safety and effectiveness of intravenous therapy with autologous BMCs alone, or in combination with metabolic cotreatment afforded by antioxidants and L-arginine, in the diabetic mouse vs nondiabetic mouse ischemic hindlimb model.…”