Vascular occlusion

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

The neuromuscular complications of diabetes mellitus are most often neuropathic in origin, with distal sensorimotor polyneuropathies being the most common. In addition, ischemic infarction of skeletal muscle may occur due to occlusive vascular disease, with small and medium-sized arterioles particularly affected. This occurs in poorly-controlled diabetes and affects thigh, muscles in most cases. In acute stages, muscle biopsy findings are those of widespread muscle necrosis, edema, and phagocytic cell infiltration. Muscle regeneration may be incomplete and increased fibrous connective tissue may replace lost muscle tissue. 

Patients with occlusive vascular disease are at high risk for further compromise of circulation to the extremities, which may result in gangrene,... 

There may be an added benefit for adults. N 5-methyltetrahydrofolate is required for the conversion of homocysteine to methionine (Figure 33-1 Figure 33-2, reaction 1). Impaired synthesis of N 5-methyltetrahydrofolate results in elevated serum concentrations of homocysteine. Data from several sources suggest a positive correlation between elevated serum homocysteine and occlusive vascular diseases such as ischemic heart disease and stroke. Clinical data suggest that the... 

Kang SS, Wong FW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992 12 279-298. 

Anti-thrombotic Trialists Collaboration Meta-analysis of trials studying antiplatelet agents in patients at high risk of occlusive vascular disease... 

Cholesterollowering drugs HPS Simvastatin versus placebo in patients with coronary disease or other occlusive vascular disease (including TIA or stroke)... 

H5 otension in (atherosclerotic) occlusive vascular disease is particularly serious, for these patients are dependent on pressure to provide the necessary blood flow in vital organs whose supplying vessels are less able to dilate. It is important to maintain an adequate mean arterial pressure, whichever inotrope is selected. 

Occlusive vascular disease is a major cause of morbidity and mortality.There is now better understanding of the mechanisms by which the haemostatic system ensures blood remains fluid within vessels, yet forms a solid plug when a vessel is breached, and of the ways in which haemostasis may be altered by drugs to prevent or reverse (lyse) pathological thrombosis. 

A patient with aorto-iliac occlusive vascular disease and hypertension suffered a stroke 6.5 minutes after administration of intravenous dipyridamole during a thallium myocardial study (11). Aminophylline did not reverse its progression. 

Intravenous administration of indometacin increases blood pressure, coronary vascular resistance, and myocardial oxygen demands, decreasing coronary flow. A controlled short-term study showed that indometacin increased blood pressure in patients with mild untreated essential hypertension (SEDA-17, 108). In view of the increasing use of parenteral administration, the acute hemodynamic effects of indometacin may now occur more often, especially in the elderly (5). The mechanism is poorly understood, but apparently a direct action is exerted on the resistance vessels in various regions. This is probably independent of indometacin s action on prostaglandin formation. The chnical relevance is largely unknown, but other NSAIDs should probably be prescribed for patients with occlusive vascular diseases affecting the cerebral and/or coronary vessels. 

In plasma, homocysteine is present as both free (< 1 %) and oxidized forms (>99%). The oxidized forms include protein (primarily albumin)-bound homocysteine mixed disulfide (80-90%), homocysteine-cysteine mixed disulfide (5-10%), and homocystine (5-10%). Several studies have shown the relationship between homocysteine and altered endothelial cell function leading to thrombosis. Thus, hyperhomocysteinemia appears to be an independent risk factor for occlusive vascular disease. Five to ten percent of the general population have mild hyperhomocysteinemia. 

B. Epinephrine is relatively contraindicated in patients with organic heart disease, peripheral arterial occlusive vascular disease with thrombosis, or ergot poisoning (see p 189). 

In one study, patients having inoperable severe occlusive vascular disease were administered 3.8 mg zinc/kg/day as zinc sulfate for at least 1 year (Henzel et al. 1971). Eighteen of the 24 patients experienced improvement in lower extremity blood flow and unchanged or decreased arterial pressure. Zinc s role in these improvements was not completely understood by the study authors. They hypothesized that when optimal zinc levels are provided to the ischemic limb, the activity of certain zinc enzymes promotes the reversal of tissue-dependent hypoxia and/or lactic acidemia in the muscles. It is also not known if this high dose of zinc was associated with any toxic effects. 

Mawad ME, Hilal SK, Michelsen WJ, Stein B et al. (1984) Occlusive vascular disease associated with cerebral arteriovenous malformations. Radiology 153 401-408... 

The largest experience to date with neurolytic thoracic and lumbar sympathetic block is in the treatment of occlusive vascular disease (Schild 1998). After sympathetic block, assessment of completeness of the interruption is best done by determining loss of sweat and a rise in skin temperature. This technique can however give rehef to patients with intractable pain caused by carcinoma, in whom conventional therapy is no longer effective (Bonica 1990b). Possible complications with thoracic sympathetic blocks include accidental puncture of the lung, puncture of intercostal vessels, or contact with the thoracic somatic nerve if the bevel... 

Homocysteine is sulfur-containing amino acid that has been linked with higher risks of coronary heart disease (CHD), stroke and other occlusive vascular diseases (Clarke et al. 1991). Untreated individuals with homocystinuria, who have extreme elevations of plasma homocysteine (typically > 100 pmol/L), have high rates of vascular disease in their second and third decades (McCully 1969 Mudd et al. 1989). Homocystinuria is caused by deficiency of the enzyme cystathionine C-synthase, required for the conversion of homocysteine to cystathionine. In addition to the associations with vascular risk, persons homozygous for homocystinuria may also have ocular, skeletal and neurologic complications of the disease. 

Jamieson WRE, Janusz MT, Miyagishima RT, et al. Influence of ischemic heart disease on early and late mortality after surgery for peripheral occlusive vascular disease. Circulation 1982 66 192-197. 

Microarray Applications in Occlusive Vascular Disease. Cardiovascular Hematological Agents in Medicinal Chemistry, Vol.9, pp. 84-94. 

The view that the nerve lesions are the outcome of degenerative atheromatous changes in the vasa nervorum has been one that has been much debated and despite the repeated reports of poor correlation between occlusive vascular disease and neuropathy it would probably be premature to exclude this as a contributory, if not a causative, factor. 

Although there are some problems with efficiency and stability of expression, the elinieal use of naked DNA is notable Ibr its simplidly and the lack of immunogenicity the latter issue being a recurring problem for the viral vectors. Plasmid DNA has alreatfy been used in one clinical trial in which vascular endothelial growth factor (VEGF) was delivered to skeletal muscle of the lower limbs in patients with severe occlusive vascular disease. 

Fish oils and co-3 polyunsaturated fatty acids exhibit hypolipidemic effects and both antiaggregatory and antiinflammatory properties (Table 1), they may lead to complex and only partially understood alterations of cellular interactions. The available data raise the question of the potential therapeutic and preventive value of dietary supplementation with co-3 polyunsaturated fatty acids in occlusive vascular diseases. 

The conclusion that diet and occlusive vascular disease are causaUy linked is based on the following clinical and experimental observations ... 

Descriptive epidemiologic studies comparing Greenland Eskimos and mainland Danes suggested that a diet rich in marine lipids may lead to a signiflcant reduction in the incidence of occlusive vascular disease (Table 2) independoit of sm differences and independent of the total amount of fat consumed [7, 8, 26, 87]. The average individual Hsh consumption of adult Eskimos following traditional dietary habits is estimated to be about 400 g/day (S, 6], i.e., four to six times more than that of mainland Danes. 

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