Peripheral arterial occlusive disease

This article updates the diagnostic and therapeutic management of patients with peripheral arterial disease.     

Thrombophilias and peripheral arterial occlusive disease

Peripheral arterial occlusive disease is a frequent disease due to the classical vascular risk factors such as smoking, diabetes mellitus, dyslipidemia, and hypertension. Despite these risk factors, many thrombophilias (physiological inhibitors defects, Factor V Leiden and 20210A prothrombin gene variant, antiphospholipid antibodies, mild hyperhomocysteinemia 15-30micromol/l) can be evoked in some clinical forms of peripheral arterial occlusive disease. This paper provides a synthesis of the published data about this topic. Screening for these thrombophilias is justified in patients with venous thromboembolic disease, or signs of antiphospholipid syndrome and possibly in different situations such as premature atheroma of lower limbs, chronic ischaemia, evolutive disease despite adapted treatment and revascularisation failures without evident technical explanation. Except for the antiphospholipid syndrome, there is currently no consensus for systematic screening of thrombophilia and treatment in patients with peripheral arterial occlusive disease.     

Interval exercise in arterial occlusive disease

During intermittent exercise with periods of six minutes with two minutes pause the fluctuations in arterial and popliteal venous blood of lactate and pyruvate as well as changes in the lactate pyruvate ratio were studied in eleven patients with claudicatio intermittens. Oxygen uptake stabilizes itself within 4-6 min during exercise and VO2 at the end of an exercise period is higher than in the beginning of recovery. The level of arterial lactate does not vary significantly. The highest venous lactate was found in the pause. Significant differences in venous lactate, pyruvate and lactate pyruvate ratio were found between the first and second exercise. It is concluded that during intermittent exercise less glycogen was used and that this glycogen saving effect seems to have been accomplished both by a shift towards more oxidative metabolism and by a greater contribution from other substrates than glycogen.     

Mesenteric arterial occlusive and aneurysmal disease

Mesenteric arterial diseases are a heterogeneic group of clinically significant illnesses that have become recognized with increasing frequency because of the more common imaging of the intestinal circulation when studying both vascular and nonvascular diseases of the abdomen. Considerable knowledge exists regarding some of these diseases, whereas the understanding of others is anecdotal. It is important for clinicians to recognize differences among common ischemic diseases and common splanchnic aneurysms.     

Dyslipoproteinemia and peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is common in older age. PAOD is associated with an increased risk of vascular events (eg, myocardial infarction or stroke). Therefore, the prevention and treatment of PAOD is important, especially at a time when the elderly population is increasing. There is an association between lipid abnormalities and the risk of developing PAOD. However, it is not yet definitively established that early intervention with lipid-lowering drugs prevents the development of PAOD. There is evidence that vascular events in patients with PAOD can be significantly reduced by statins and that the symptoms associated with PAOD are improved by this treatment. There is an urgent need for appropriately designed lipid-lowering trials in patients with PAOD.     

Anatomic and functional diagnosis in arterial occlusive disease

Arteriosclerosis is the most common cause of peripheral arterial disease (PAD); it begins in the second and third decades of life but first becomes manifest, however, many years later. The hemodynamic effects of arterial narrowing in the peripheral arteries are dependent on functional and morphological adaption, temporal and topographical factors and the prevailing metabolism. In the large arteries of the legs, luminal narrowing of more than 70% is required to render impairment of normal exercise capacity such that it can be assumed that even substantial vascular changes may not be associated with clinical symptoms. An acute peripheral vascular occlusion is regarded as a medical emergency. The most frequent cause is in-situ thrombosis or embolism; the most common sources of embolism are valvular lesions in the left side of the heart and thrombi in the left ventricle after myocardial infarction. Sites of predilection for emboli are acutely-angled branching points of arteries primarily in the lower extremities (aorta, iliac, femoral and popliteal arteries). With the exception of the deep femoral artery, the statement is generally valid that the more central the occlusion, the more severe are the effects anticipated. In-situ arterial thrombosis superimposed on a preexistent arteriosclerotic stenosis or after vascular reconstruction, leads to occlusions generally in the pelvic region or upper thigh. Further causes of acute local vascular occlusion are pressure, tension or kinking at the artery, rarely trauma, dissecting aneurysm or ergotism. In 90% of patients with PAD there is involvement of the lower extremity, apparently due to the effects of hydrostatic pressure. Three types of disease can be differentiated: the pelvic type which is observed in approximately one-third of all cases. Through occlusion of the distal aorta (Leriche syndrome) or the large iliac vessels, vice-like pain is incurred in the hip musculature which frequently radiates to the upper thighs; with bilateral occlusion, impotence develops.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doppler diagnosis in peripheral arterial occlusive disease

PHYSICAL AND TECHNICAL FUNDAMENTALS OF DOPPLER ULTRASONOGRAPHIC METHODS: In addition to units recording both velocity and direction of blood flow, mostly using two ultrasonic frequencies and phase-out technique, there are small non-directional units available which provide useful diagnostic information from the acoustic Doppler signal derived. Doppler ultrasonic techniques utilize two physical phenomena: a) High-frequency ultrasonic energy penetrates biologic tissue and is partially reflected at borders between tissues of differing density. b) If the border area is in motion, due to the Doppler effect, there is a change in the reflected ultrasonic frequency with respect to the frequency emitted. In blood vessels the ultrasonic beam is primarily reflected from the flowing red blood cells where the change in frequency is a function of the velocity of flow (Doppler effect). From the Doppler transducer, the continuously-emitted ultrasonic beam is also received after being reflected. The frequency of the reflected beam is directly proportional to the velocity of the flowing blood. If flow is directed toward the transducer, the frequency of the reflected beam increases and if the flow is away from the transducer, the converse is true. The best Doppler signals can be received when the angle beta of the transducer to the studied vessel is about 45 degrees. The unprocessed Doppler signal represents a frequency spectrum corresponding to the various velocities of the individual lamina of the blood stream from which the prevailing velocity is integrated and registered. The penetration depth is dependent on the frequency emitted. Doppler units are preferred with working frequencies of 8 to 10 MHz and 3 to 5 MHz. With 8 MHz, the maximal depth of penetration is 3.5 cm, with 4 MHz, 8 cm. The lowest detectable velocity is also dependent on the frequency emitted: with 8 MHz, minimum is 3 cm/s. Since flow toward the transducer results in a positive Doppler shift and flow away in a negative shift, with the Doppler signal, the direction of flow can also be determined. The recorded Doppler curves enable a qualitative and, to some degree, quantitative assessment. Phase-out and frequency analysis systems enable differentiation of forward and backward flow components. From separate forward and backward flow curves, the instantaneous summation curve (integrated instantaneous hemotachygram) as well as a trend curve over 5 to 7 seconds can be constructed and the mean flow velocity displayed.     

Exercise testing in lower-extremity arterial occlusive disease

Exercise tolerance testing has wide application in the detection and quantitation of lower-extremity claudication. Serial follow-up after operative or nonoperative therapy permits an accurate, objective assessment of the course of the disease in each limb. Unmasking of occult aortoiliac disease, identification of pseudoclaudication, and assessment of the relative contribution of other systemic disorders in exercise limitation are further advantages of this technique. Routine exercise tolerance testing has merit for the initial and subsequent evaluations when symptoms of leg pain are produced solely by exercise.     

Conservative therapy of arterial occlusive disease

Since in stage II of peripheral arterial disease (PAD), according to the definition, there is no objective evidence of danger for the involved extremity, management is dependent on the extent to which the claudication complaints are tolerated (Figure 1). If well tolerated, observation and treatment of risk factors, possibly enrollment in an out-patient training group, are sufficient. Exceptions are the cases of pending danger to viability as well as isolated stenoses in the pelvic region or larger leg arteries easily amendable to percutaneous dilatation. If the patient does not tolerate the complaints, for aortic and pelvic artery occlusions, training of the muscles of the upper thigh is indicated, for occlusions in the thigh training of the calf musculature is warranted. The pathophysiologic basis of training lies in an increase in perfusion via collaterals due to dilatation of the muscular arterioles distal to the stenosis incurred by virtue of work and ischemia. This mechanism may also involve a sheer-induced release of endothelium-derived relaxing factor. Over a moderate period of time, there is an organic increase in collateral caliber due to the perfusion-dependent growth stimulus. A further effect of training is an increase in metabolic activity. If training is unsuccessful, lumen enlarging measures ("LEM" in Figure 1) should be considered. Indications for percutaneous transluminal angioplasty (PTA) are stenoses in the pelvic region or large leg arteries as well as short occlusions of the femoropopliteal vessels (less than 10 cm). With the help of special techniques like rotational angioplasty even occlusions of the pelvic arteries are treatable in selected cases. The five-year patency rate of dilated pelvic artery stenoses is 82%, three-year patency rate for femoral artery stenoses 81% and femoral artery occlusions 78%. Among newer procedures are laser and auger angioplasty, catheter atherectomy and stents. The question of efficacy of platelet inhibiting drugs of the aspirin type, with regard to prophylaxis of early and late re-stenosis remains unsettled. In principle new medical approaches are selective inhibition of thromboxane as well as inhibition of arteriosclerosis-induced proliferation and migration of active mediamyocytes, for example, with highly negative-charged polyanions. For the prophylaxis of peripheral arterial occlusion with aspirin, a dosage of one to 1.5 gram daily would seem appropriate until studies are available to document the effects of lower dosages.(ABSTRACT TRUNCATED AT 400 WORDS)     

Peripheral arterial occlusive disease of the lower extremities

Disturbance of the arterial perfusion of the lower limbs with occlusion in the aorto-iliac area presents a broad field of operative treatment in younger patients below 70 years of age. In older people caution is necessary depending on preexisting multiple morbidity. If necessary, extra-anatomic bypass operations have to be taken into consideration in order to save a jeopardized leg. Limb salvage should be accomplished whenever possible. In case of involvement of the femoro-popliteal region even in old age patients aggressive surgery for limb salvage is important because of high mortality due to primary amputation and last not least because of better life quality and for cardiovascular training. Conservative treatment of occlusions in the aorto-iliac area is not promising much success. Therefore in this area vascular surgery is the treatment of choice. In contrary arterial occlusion of the femoro-popliteocrural region--especially if both are combined--can be positively influenced by conservative angiological regimen. Hence conservative therapy should always be tried first, before difficult and long lasting vascular reconstructions are taken into consideration. One should not forget that surgery of occlusive vascular disease is only a symptomatic therapy, not a curative one. Life expectancy is not enhanced, but only ability of walking is saved. Generally spoken, the patient with occlusive vascular disease of the lower limbs nowadays can be offered a differentiated and individualized therapy including, also, non-surgical procedures. Well planned reconstructive vascular surgery has a good long time prognosis saving the physical integrity and efficiency of the older patient suffering from disabling vascular alterations.     

Inflammation and platelet activation in peripheral arterial occlusive disease

OBJECTIVES

Epidemiological evidence indicates that inflammation accompanies the progression of atherosclerosis. The aim of the present cross-sectional study was to define relationships between platelet activation and inflammation in patients with mild to severe (stages II to IV) peripheral arterial occlusive disease (PAOD) and matched controls. The effect of chronic administration of low-dose acetylsalicylic acid was investigated.

METHODS

Subjects were studied on a single occasion. C-reactive protein (CRP) and two indexes of in vivo platelet activation were measured – the urinary excretion of 11-dehydrothromboxane (TX) B₂ by immunoassay and circulating platelet-monocyte aggregates (PMAs) by flow cytometry.

RESULTS

Plasma PMAs and urinary 11-dehydro-TXB₂ were significantly increased in PAOD patients compared with controls (P<0.01 for all). A positive correlation between 11-dehydro-TXB₂ and CRP was found in the study population (r_s=0.63, P<0.001). Using logistic regression analysis, CRP was the only independent correlate of 11-dehydro-TXB₂ (β_CRP=11.9, P<0.01), whereas only the presence of PAOD was an independent predictor of high PMA levels (β_PAOD=13.7, P=0.001). Chronic administration of acetylsalicylic acid reduced 11-dehydro-TXB₂, but not PMA and CRP.

CONCLUSIONS

There is evidence that platelet activation in patients with PAOD is related to the vascular disease and is dependent on the severity of inflammation.     

Adiponectin and inflammatory markers in peripheral arterial occlusive disease

This study was designed to examine the plasma levels of adiponectin as well as markers of inflammation and endothelial function in peripheral arterial occlusive disease (PAOD), and to investigate the pathophysiological significance of adiponectin in this disease. Eighty-eight subjects with (n=40) and without PAOD (n=48) were enrolled. Multiple regression analysis including age, sex, body mass index, hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, creatinine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecules-1 (sVCAM-1), von Willebrand factor, and high-sensitive C reactive protein (Hs-CRP) showed that adiponectin concentration was significantly lower in PAOD subjects (PAOD: 7.9+/-0.7 microg/mL versus without PAOD: 9.5+/-0.6 microg/mL, F=4.94, p<0.03). Furthermore, concentrations of adiponectin (F=8.5, p<0.01) as well as sICAM-1 (F=5.8, p<0.02), sVCAM-1 (F=5.9, p<0.02), and Hs-CRP (F=3.8, p=0.05) were independently associated with ankle-brachial index. In 27 subjects (10 with PAOD and 17 without PAOD), adiponectin levels in the femoral artery and saphenous vein were measured. A significant step-up of adiponectin from the artery to the vein was observed in subjects without PAOD (+13.0%, p<0.01), but not in subjects with PAOD (+0.4%, NS). Plasma adiponectin as well as Hs-CRP were followed before and after percutaneous transluminal angioplasty (PTA) in eight patients. Adiponectin showed a tendency to decrease after PTA (day 6, -30.6%), although Hs-CRP significantly increased. Adiponectin is decreased in patients with PAOD in proportion to the severity of the disease. Adiponectin concentration could be a marker of the existence of atherosclerosis, and measurement of its concentration may be helpful in assessment of the progress of atherosclerosis.     

Placebo-controlled, double-blind trial of hemodilution in peripheral occlusive arterial disease

A number of uncontrolled trials has suggested that hemodilution is effective in peripheral occlusive arterial disease. This study was aimed at proving or disproving the efficacy of hemodilution by using a randomized, placebo-controlled, double-blind crossover design. Twenty-four stable claudicants with long, collateralized femoropopliteal obstructions were treated with isovolemic hemodilution with 500 mL of 10% hydroxyethyl starch 200 and sham dilutions. Three weeks of hemodilution lowered blood and plasma viscosity, as well as hematocrit, and increased resting blood flow and pain-free walking distance. Placebo treatments produced no such favorable changes. It is concluded that hemodilution therapy can be clinically effective in patients with arterial obstructions in the lower extremities. Hemodilution seems particularly promising under hemodynamic condition of low shear stresses in vivo.