Biomedical Engineering Reference
In-Depth Information
Peripheral Vascular Disorders
Peripheral Atherosclerotic Arterial Disease
As mentioned earlier in the report, atherosclerosis is an inflammatory disease in
which there is an increase in active inflammation markers such as C-reactive pro-
tein and other factors released by endothelial cells. Nitroglycerin acts by a chemical
liberation of NO, which explains its anti-inflammatory action. In a randomized,
double-blind, placebo-controlled pilot study, patients were treated with continuous
application of a transdermal nitroglycerin patch (de Berrazueta et al.
2003
). No
biological parameter was modified in the placebo group but nitroglycerin signifi-
cantly reduced plasma levels of C-reactive protein and sE-selectin and increased
the levels of intraplatelet cGMP. The results show that nitroglycerin has an anti-
inflammatory action in patients with peripheral vascular disease. This may provide
a new therapeutic approach to understanding the efficacy of nitrovasodilators in the
improvement of atherosclerotic syndromes.
Peripheral Ischemic Disease
Lower-limb ischemia is a major health problem. Critical limb ischemia due to
advanced peripheral arterial occlusive disease (PAOD) is characterized by reduced
blood flow and oxygen delivery with exercise or even at rest with severe disease,
resulting in claudication (muscle pain) and eventual non-healing skin ulcers that
can lead to gangrene. The estimated incidence of critical limb ischemia is 500-1,000/
million/year in the USA. Progressive microcirculatory dysfunction and impairment
of angiogenesis/arteriogenesis are crucial pathophysiologic determinants of critical
limb ischemia. As critical limb ischemia progresses, deregulation of the microcir-
culation occurs, characterized by activation of white blood cells, platelet aggrega-
tion, plugging of capillaries, endothelial damage, and release of free radicals, all of
which promote further ischemia leading to tissue damage and eventual tissue necrosis.
The prognosis of patients with critical limb ischemia is poor. The survival rate for
patients with significant tissue necrosis without major amputation is less than 50%
after 1 year. Many patients presenting with ischemic pain and ulcers are not suitable
candidates for surgical revascularization or angioplasty due to diffuse, distal occlu-
sive vascular disease. Current pharmacotherapy has had little impact on limb sal-
vage in patients with advanced critical limb ischemia and, likewise, little
symptomatic effect.
Because of the absence of effective treatment in the advanced stages of the dis-
ease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeu-
tic approaches include the intramuscular use of autologous bone marrow cells
(BMCs). Because tissue ischemia is associated with an overwhelming generation
of oxygen radicals and perturbed shear stress, metabolic intervention with antioxi-
dants and L-arginine could potentially induce beneficial effects beyond those
achieved by BMCs. The protective effect of autologous BMCs and vascular pro-
tection by metabolic cotreatment (vitamin E added to the chow and vitamin C
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