Critical limb ischemia

Baumgartner, L, Pieczek, A, Manor, O., Blair, R., Kearney, M., Walsh, K. et al. (1998) Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation, 97, 1114-1123. 

Allie DE, Hebert CJ, Lirtzman MD, et al. A safety and feasibility report of combined direct thrombin and GP llb/llla inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention treating critical limb ischemia like acute coronary syndrome. J Invasive Cardiol 2005 17 427-432. 

A small study of plasmid-derived VEGF showed collateral vessel growth and improved outcome in patients with critical limb ischemia (37), In the regional angiogenesis with VEGF (RAVE) study, AdVEGF-121 was injected into the skeletal muscle of the lower extremity and safety and efficacy were compared with placebo control in patients with unilateral, severe, disabling intermittent claudication. No symptomatic or objective evidence of clinical benefit were reported at 26-week follow-up (38). 

Masaki I, Yonemitsu Y Yamashita A, et al. Angiogenic gene therapy for experimental critical limb ischemia acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res 2002 90(9) 966-973,... 

The clinical manifestations of PAD are associated with reduction in functional capacity and quality of life, but because of the systemic nature of the atherosclerotic process there is a strong association with coronary and carotid artery disease. Consequently, patients with PAD have an increased risk of cardiovascular and cerebrovascular ischemic events [myocardial infarction (Ml), ischemic stroke, and death] compared to the general population (4,5). In addition, these cardiovascular ischemic events are more frequent than ischemic limb events in any lower extremity PAD cohort, whether individuals present without symptoms or with atypical leg pain, classic claudication, or critical limb ischemia (6). Therefore, aggressive treatment of known risk factors for progression of atherosclerosis is warranted. In addition to tobacco cessation, encouragement of daily exercise and use of a low cholesterol, low salt diet, PAD patients should be offered therapies to reduce lipid levels, control blood pressure, control blood glucose in patients with diabetes mellitus, and offer other effective antiatherosclerotic strategies. A recent position paper... 

Hirsch AT. Critical limb ischemia and stem cell research anchoring hope with informed adverse event reporting. Circulation 2006 114 2581-2583. 

Rajagopalan S, Olin J, Deitcher S, Pieczek A, Laird J, Gross-man PM, Goldman CK, McEllin K, Kelly R, Chronos N. Use of a constitutively active hypoxia-inducible factor-1 alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients phase I dose-escalation experience. Circulation 2007 115 1234-1243. 

In a placebo-controlled trial in 114 patients with critical limb ischemia, twice-daily intravenous pentoxifylline 600 mg produced unimpressive results (4). 

Walter, D.H., Krankenberg, H., Balzer, J.O., Kalka, C., Baumgartner, I., Schluter, M., Tonn, T., Seeger, F., Dimmeler, S., Lindhoff-Last, E., Zeiher, A.M., Investigators, P. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia A randomized-start, placeho-controUed pilot trial (provasa). Circulation. Cardiovascular Interventions 4, 26-37 (2011)... 

Bosiers M, Scheinert D, Peeters P, TorseUo G, Zeller T, Deloose K, et al. Randomized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease. J Vase Surg 2012 55(2) 390-8. 

Matia I, Janou ek L, Marada T and Adamec M. Cold-stored venous allografts in the treatment of critical limb ischemia. Eur. J. Vase. Endovase. Surg. 34 429 31,2007. 

Lower-extremity CTA can be performed with all currently available MDCT scanners. No special hardware is required. Because of the slightly thicker sections (2.5-3 mm) usually obtained with four-channel MDCT (4 X 2.5 mm), evaluation of crural and pedal arteries is slightly limited, notably if calcifications are present. The technical limitations of four-channel MDCT are only clinically problematic in a small subset of patients, such as individuals with critical limb ischemia who have no or mild inflow and femoropopliteal disease, and who have diseased and calcified infrapopliteal vessels. In the majority of patients—notably those with intermittent claudication where interventions are limited to aboveknee arteries—even four-channel MDCT can provide all the therapeutically relevant information (Heijen-brok-Kal et al. 2007 Rubin et al. 2001 Ofer et al. 2003 Martin et al. 2003 Ota et al. 2004 Catalano et al. 2004). 

There are three levels of occlusive disease in the lower limb arteries aortoiliac, femoropopliteal, and infrapopliteal disease. Disease confined to one level may be asymptomatic or it can present with intermittent claudication. The presence of two or three levels of disease are symptomatic, and patients usually present with severe claudication or rest pain. Three levels of disease are often seen in patients with skin damage and critical limb ischemia. Without an intervention most limbs with critical ischemia will be amputated within 1 year. In patients with diabetes mellitus the disease is usually confined in the infrapopliteal vessels. Such patients may develop critical limb ischemia with one level of disease because this is the most distal of the three. Usually, multiple stenoses and/or occlusions are found in at least two of the run-off arteries. Although it is known that atherosclerosis develops most often in bifurcations, in the lower extremities the most frequently involved site is the superficial femoral artery. Other common sites are the aortoiliac, iliac, femoral popliteal, and tibioperoneal trunk bifurcations. 

Skin perfusion pressure measurements are taken with laser Doppler. Skin perfusion pressure is used in patients with critical limb ischemia requiring surgical reconstruction or amputation. Like the toe pressures, it is useful in patients with falsely elevated pressures caused by arterial wall calcification. 

Intramuscuiar gene therapy in chronic critical limb ischemia. 

In 1992, Johnston and colleagues (68) published re-analyzed data regarding angioplasty of the femoral and popliteal arteries. Of a total of 254 patients, 50 (19.7%) underwent femoropopliteal angioplasty with the intent of limb salvage for critical limb ischemia. Whereas the overall... 

Bastounis E, Georgopolis S, Maltezos C, et al. PTFE-vein composite grafts for critical limb ischemia A valuable alternative to all-autogenous infrageniculate Teconstmetions. Eur J Vase Endovasc Surg 1999 18 127-132. 

Prager M, Holzenbein T, Aslim E, et al. Fresh arterial homograft transplantation A novel concept for critical limb ischemia. Eur J Vase Endovase Surg 2002 24 314-321. 

Vraux H, Hammer F, Verhelst R, et al. Subintimal angioplasty of tibial vessel occlusions in the treatment of critical limb ischemia mid-term results. EurJ Vase Endovasc Surg 2000 20 441-446. 

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