Stable Claudicants Research Articles

Inflammatory Profiling of Peripheral Arterial Disease

The progression of peripheral arterial disease (PAD) is poorly understood but may be caused by an underlying inflammatory dysfunction. This study therefore profiled interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, anticardiolipin, and anti-beta2-glycoprotein 1 antibody concentrations and characterized patients' inflammatory response in vitro. Patients were classified according to World Health Organization criteria and ankle-brachial pressure index into critical ischemics (n=20), stable claudicants (n=20), and controls (n=20). In vitro studies involved culturing whole blood with RPMI-1640 for 24hr with and without 1 microg/mL lipopolysaccharide and profiling cytokine production. Autoantibody levels were measured using enzyme-linked immunosorbent assays, while cytokine profiles were determined by multiplex immunoassay. Serum IL-6, IL-10, IL-13, and anti-beta2-glycoprotein 1 antibody levels were higher in PAD (p<0.05). In the case of IL-6 and anti-beta2-glycoprotein 1 antibody, levels reflected increasing disease severity (p<0.05). In vitro studies revealed that IL-8 and IL-13 secretory capacities were significantly higher in PAD after 6 hr. However, when these were standardized against patient leukocyte count, cytokine production profiles did not differ. PAD features an increased inflammatory burden irrespective of Th1:Th2 cytokine type; this is more pronounced with increasing disease severity. However, the inflammatory hyperresponsiveness of cultured whole blood from PAD patients probably relates to associated leukocytosis, rather than being attributable to an inherent inflammatory dysfunction.

Inflammatory trends of Interleukin‐7 in peripheral arterial disease

Objective: The primary function of interleukin (IL)-7 is the regulation of T-cell homeostasis and existing literature implicates it as a pro-inflammatory cytokine in atherosclerosis. In coronary artery disease, higher plasma levels of IL-7 have been found in patients with unstable angina compared to controls and patients with stable angina. Therefore, this study examined whether IL-7 levels behaved similarly in peripheral arterial disease (PAD). Method: Following Ethics approval, plasma was isolated from 39 patients (9 control, 15 stable claudicants, SC; 15 critical ischaemics, CLI). PAD diagnosis included Fontaine classification, ABPI and radiology. IL-7 levels were determined by fluid-phase immunoassay. Results: Although plasma levels of IL-7 were lower in the PAD group compared to controls (P<0.05), there were no significant differences in profiles between stable claudicant and critically ischaemic subgroups. Conclusion: Contrary to expectations, IL-7 levels were lower in association with PAD. These observations may be accounted for by the fact that none of the PAD patients in this study had acute ischaemia, which would otherwise result in activated platelet-induced IL-7 production. Furthermore, all PAD patients were on aspirin, which has previously been shown to reduce IL-7 levels in vitro. Project supported by LGI vascular surgical research fund. Figure 1Open in figure viewerPowerPoint IL-7 levels in control and PAD patients (∗P<0.05).

In vivo cytokine profiling in peripheral arterial disease (PAD)

Objective: This study determined Th1:Th2-type cytokine balance in relation to PAD severity. Methods: Following ethics approval, plasma was isolated from 10 controls, 14 stable claudicants (SC), 14 critical ischaemics (CLI). PAD diagnosis included Fontaine classification, ABPI and radiology. Th1 (interleukin (IL)-6, IL-12(p70), interferon (IFN)-γ) and Th2 (IL-10) cytokine profiles were measured by multiplex immunoassay. Results: IL-6 levels tended to increase in PAD, primarily with CLI, in contrast to IL-12(p70). IL-6:IL-10 ratio was higher in PAD, particularly with CLI, as opposed to IL-12(p70):IL-10 ratio (P<0.05). PAD had no effect on IFN-γ:IL-10 ratio. Conclusion: Estimation of Th1:Th2 cytokine ratios probably provide a more sensitive measure of disease progression and are more representative of in vivo cytokine synergism. Project supported by LGI vascular surgical research fund. Table 1. Cytokines and ratios in PAD (different superscripts = significant differences between groups/∗significantly different to controls; P<0.05)

Short-term Lipid-Lowering Treatment with Atorvastatin Improves Renal Function But Not Renal Blood Flow Indices in Patients with Peripheral Arterial Disease

Some studies have suggested that lipid lowering with statins exerts favorable effects on the progression of chronic kidney disease. Therefore, the authors assessed the effects of short-term atorvastatin treatment on biochemical markers of renal function and evaluated duplex indices of renal blood flow (RBF) in patients with peripheral arterial disease. Hyperlipidemic claudicants (n = 18), aged 44-85 years, were treated for 8 weeks with 20 mg/day atorvastatin. Blood tests at baseline and after 8 weeks included serum fasting lipids, creatinine, urate, and cystatin C (a sensitive indicator of renal function) levels. RBF was also assessed (n = 9) by measuring pulsatile and resistance duplex indices. As expected, there was a significant improvement in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. There was also a significant (p < 0.0001) fall in serum creatinine from 89 (58-125) to 79 micromol/L (54-119) and an increase in calculated creatinine clearance (CrCl) from 72 (40-129) to 80 mL/minute (47-138; p < 0.0001). Serum cystatin C values decreased significantly (p = 0.0002) from 1.04 (0.57-1.56) to 0.90 mg/L (0.47-1.47). There were no detectable changes in the RBF duplex indices. Treatment of stable claudicants with atorvastatin for 8 weeks was associated with improved renal function (as assessed by serum creatinine, cystatin C, and calculated CrCl) without changes in RBF. Further studies are required to identify the mechanisms involved in this phenomenon.

Effect of weight on claudication distance

Conservative measures to improve claudication distance include advice on smoking, exercise, diet and weight reduction. Although the effects of smoking, exercise and diet are established, the effect of weight is less clear. The aim of this study was to investigate the effect of carrying extra weight on the maximum walking distance in stable claudicants. Twenty stable claudicants were exercised on a treadmill (3.5 km/h, 0 degrees slope) carrying 0, 2.5, 5, 7.5 and 10 kg weights in randomized sequence. Maximum claudication distance and ankle: brachial pressure indices were recorded. Patients were categorized into mild or severe claudicants depending on their ability to walk 200 m. A response index (RI) was calculated as the reduction in claudication distance per kilogram load; RI = [CD0-CD10]/10 m/kg, where CD0 and CD10 represent claudication distance with 0 and 10 kg weights, respectively. Claudication distance was significantly reduced in subjects carrying 5 kg or more (P less than 0.01). A linear relationship was demonstrated between the mean claudication distance and the load carried (r = 0.98, P less than 0.01) with a mean response index of 10.2 m/kg. The mean(s.e.m.) RI in mild claudicants (25.9(9.5) m/kg) was greater than the value observed in the severe claudicants (3.3(0.8) m/kg; P less than 0.01, Mann-Whitney U test). This study demonstrates that weight adversely affects claudication distance and suggests that weight reduction may deserve greater emphasis in the management of some patients with intermittent claudication.

The Role of Endothelial Cell Reactive Antibodies in Peripheral Arterial Disease

ObjectivesIt is hypothesised that endothelial cell reactive antibodies (ECRA) play a role in the progression of PAD through activation of endothelial cells and the release of inflammatory cytokines. We aimed to test this hypothesis by assessing levels of ECRA, E-selectin and IL-6 in patients with PAD of varying severity in a case controlled study. Design, materials, methodsPatients were assessed clinically and with ankle–brachial pressure indices. Patients with critical ischaemia (CI, n=30), stable claudicants (SC, n=30), and age-matched controls (AMC, n=20) were studied. Antibody, E-selectin and IL-6 levels were measured using ELISA. ResultsECRA levels were significantly raised in the CI group over AMC.IL-6 levels were significantly elevated in both SC and CI over the control group and in CI over SC.There were no significant differences in E-selectin levels between the AMC, SC and CI. ConclusionOur findings support the hypothesis that autoantibodies play a role in promoting PAD by elevating IL-6. The absence of an elevation in E-selectin in this study may be due to its short half-life, and casts doubt on its value as a marker of inflammation in atherosclerosis.

Chronic Transcutaneous Electrical Stimulation of Calf Muscles Improves Functional Capacity without Inducing Systemic Inflammation in Claudicants

Objectives. To assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability.Design. Prospective randomised controlled trial of calf muscle stimulation.Materials and methods. Stable claudicants were randomised to receive either active chronic low frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one leg, 3×20 min per day for four weeks. Leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (ACR), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention.Results. Acute active muscle stimulation activated leucocytes less (28% increase) than a standard treadmill test (81% increase) and did not increase ACR. Chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70, P<0.05) while control treatment had no effect. Active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force.Conclusions. Chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.

The intermittent claudication questionnaire: A patient-assessed condition-specific health outcome measure

As yet, there is no patient-assessed, condition-specific instrument for the assessment of health-related quality of life in intermittent claudication. We evaluated the intermittent claudication questionnaire (ICQ) for properties required of a measure of health outcome. Interviews with patients with intermittent claudication and vascular specialist opinion produced a pool of statements used to itemize a self-completed ICQ. This was piloted in 20 patients for practicality and then administered to 124 stable claudicants. Reliability was assessed through a retest in 63 (51%) patients at 14 days and analysis of Cronbach's alpha for internal consistency. Spearman's correlation coefficient was used to assess construct validity in comparisons between the ICQ and ankle brachial pressure index, treadmill-walking distances, the walking impairment questionnaire, the EuroQol, and the Short Form-36. Responsiveness of the ICQ to changes in health was assessed in 60 patients treated conservatively and 40 patients undergoing angioplasty. The standardized response mean was used to identify the most responsive instrument in the study. A 16-item ICQ with a test-retest intraclass correlation of 0.95 and Cronbach's alpha of.94 was produced. One hundred twenty-one (98%) patients completed the ICQ (mean time, 3.7 minutes). The ICQ correlated better with the EuroQol (r = 0.58) and 7 out of 8 subscales of the Short Form-36 (r = 0.33-0.68) compared with the walking impairment questionnaire. The ICQ demonstrated the largest standardized response mean in relation to health transition compared with the other instruments. The patient-assessed ICQ is a practical, reliable, valid, and responsive measure of patient health-related quality of life in intermittent claudication.

Vascular 07

Aim: The course of peripheral arterial occlusive disease in patients with isolated SFA occlusion is benign. In light of the atheroprotective role of high shear-stress, we hypothesized that the haemodynamic and shear-stress alterations in distal arteries subsequent to SFA occlusion may confer atheroprotection; we determined the mean-shear-stress in the popliteal artery of stable claudicants with SFA occlusion in comparison with normal controls matched for age and sex. Methods: We measured popliteal artery diameter, mean velocity [MV] and flow [MQ] 2 cm distal to medial femoral condyle, on recumbency, using real-time gated Doppler/duplex in 50 limbs with SFA occlusion and 37 normal control limbs. Blood viscosity was calculated from plasma viscosity and haematocrit. Mean-shear-rate = 4MQ/π (Diameter/2)3; mean-shear-stress[dynes cm−2] = mean-shear-rate• viscosity. Data presented as median (interquartiles). Results: Arteriopaths' plasma viscosity [1.83(1.78–1.94)] mPa s−1 was similar to control [1.78(1.7–1.97)] mPa s−1. Conclusions: Popliteal artery mean-shear-stress in SFA occlusion is significantly higher than in normals, mainly due to higher MV and smaller diameter. Our data suggests that enhancement in haemodynamic shear forces distal to SFA occlusion may act atheroprotectively contributing to the benign vascular outcome in this pattern of disease.

Peripheral sympathetic autoregulation in arterial calf inflow enhancement with intermittent pneumatic compression.

Peroperative mortality, graft failure and balloon angioplasty limitations mitigate against active intervention for claudication. With the exception of exercise programmes, conservative treatments yield limited results. Intermittent pneumatic compression of the foot (IPC(foot)) used daily for over 3 months enhances significantly the walking ability and pressure indices of stable claudicants; this is attributable to the significant calf inflow enhancement with IPC(foot); however, the physiologic mechanisms involved are only partially understood. Aims by comparing the effects of IPC(foot)and postural alteration on calf inflow haemodynamics, this study examines the role of peripheral sympathetic autoregulation, which controls homeostasis in lower limb vessels when posture changes, in the enhancement of calf inflow with IPC(foot)in healthy subjects and claudicants. forty-one limbs of healthy subjects (n =34; Group I) and 48 limbs of stable claudicants (Fontaine II) (n =42; Group II) were studied. The volume flow (Q), pulsatility index (PI), mean (mV), peak systolic (PSV) and end diastolic (EDV) velocities were measured in the popliteal artery using duplex ultrasound in: the horizontal position, and on sitting with or without IPC(foot). in Group II: median Q, mV, PSV and EDV increased by 61%, 53%, 29% and 51% respectively, and PI decreased by 20% as posture changed from sitting to horizontal; with IPC(foot)median Q, mV, PSV and EDV increased by 70%, 58%, 22% and 75% respectively, and PI decreased by 26% (all p < 0.001). In Group I: median Q, mV, PSV and EDV increased by 125%, 115%, 51% and 38% respectively and PI decreased by 30% as posture changed from sitting to horizontal; with IPC(foot)median Q, mV, PSV and EDV increased by 119%, 153%, 23% and 46%, respectively, and PI decreased by 50% (all p < 0.001). The effects of IPC(foot)and postural alteration (from sitting to horizontal) did not differ haemodynamically (p > 0.1) in both groups. Q on lying was similar in Groups I and II. On sitting Q was higher in Group II [p =0.027 (95% CI 1.7, 27 ml/min)]. the striking similarity in the haemodynamic effects of IPC(foot)and postural alteration in the popliteal artery strongly suggests that the leg inflow enhancement with IPC(foot)is mediated by a transient suspension of peripheral sympathetic autoregulation. In addition to their role as clinical markers of PVD severity, the autoregulatory reflexes of peripheral circulation appear to have functions with significant clinical implications in the management of patients with leg inflow impairment.

Improvement in walking ability, ankle pressure indices and quality of life in vascular claudication using intermittent pneumatic foot and calf compression: a randomized controlled trial

Abstract Background Perioperative mortality, graft failure and limitations of balloon angioplasty mitigate against active intervention for claudication. With the exception of exercise programmes, conservative treatments yield modest results. Intermittent pneumatic compression (IPC) of the foot used daily for over 3 months enhances significantly the walking ability and pressure indices of stable claudicants. This prospective randomized study evaluated the effects of IPC of the foot and calf simultaneously (IPCfoot + calf) on the walking ability, arterial haemodynamics and quality of life of patients with intermittent claudication. Methods Forty-one stable claudicants, meeting stringent inclusion and exclusion criteria, were randomized to receive either IPCfoot + calf and 75 mg aspirin (group 1; n = 21) or 75 mg aspirin alone (group 2; n = 20), with stratification for diabetes and smoking. Groups matched for age, sex, initial (ICD) and absolute (ACD) claudication distance, ankle: brachial pressure index (ABPI), popliteal artery flow (Q) and quality of life (Short Form (SF) 36 questionnaire). IPCfoot + calf (120 mmHg, three cycles per min, inflation 4 s, proximal inflate delay 1 s) was used for 2·5 h daily for 5 months consecutively. Both groups were advised to exercise unsupervised. Evaluation of patients, after randomization, included: (a) ICD and ACD on a treadmill, (b) resting and postexercise ABPIs, (c) Q using duplex imaging, and (d) quality of life. Study time-points were: baseline and 1, 2, 3, 4, 5 and 17 months. Compliance was assessed by means of a log book. Non-parametric statistical analysis was used (Wilcoxon and Mann–Whitney tests). Results After 5 months of IPCfoot + calf median ICD, ACD, resting and postexercise ABPI in group 1 increased by 197, 212, 17 and 64 per cent (all P &amp;lt; 0·001) respectively; changes in group 2 were all non-significant (P &amp;gt; 0·1). On intergroup comparison at 5 months, patients in group 1 were better than those in group 2 in terms of ICD, ACD, resting and postexercise ABPI (all P &amp;lt; 0·01). Q changes within this period were not significant in either group; neither were intergroup Q differences (P &amp;gt; 0·1). Associated changes in the quality of life within group 1 at the end of month 5 were significant; non-significant changes were noted in group 2. At 5 months patients in group 1 enjoyed a better quality of life than those in group 2 (P &amp;lt; 0·01). IPCfoot + calf use did not result in any complications. The daily IPCfoot + calf compliance (2·5 h per day) was greater than 82 per cent in the first month and greater than 85 per cent in months 2–5. One year after the end of IPCfoot + calf application, patients in group 1 maintained the improved ABPI and walking benefit. Conclusion IPCfoot + calf emerged as an effective, high-compliance, uncomplicated method for improving the walking ability and pressure indices in patients with stable claudication, with a confirmed durable outcome. These changes are associated with a significant improvement in all aspects of quality of life evaluated by the SF-36. Despite a limited benefit noted in some individuals, unsupervised exercise had a non-significant impact overall.

Antioxidants Reduce Oxidative Stress in Claudicants

Background. Low-grade ischemia–reperfusion in claudicants leads to damage of local tissues and remote organs. Since this damage is partly caused by oxygen-derived free radicals (ODFR), scavenging these ODFR could reduce the local and remote injury.Methods. Using a new method by which a free radical reaction product (ortho-APOH) of the exogenous marker antipyrine is measured to quantify the oxidative stress, 16 stable claudicants performed a standard walking test before and after administration of vitamin E (200 mg) and vitamin C (500 mg) daily for 4 weeks.Findings. Ortho-APOH was significantly increased during the reperfusion period (P = 0.026) before administration of the vitamins. After 4 weeks of vitamin supplementation no rise was found in the reperfusion period. Malondialdehyde showed no changes in either group.Interpretation. These findings indicate that administering extra antioxidants to claudicants reduces oxidative stress in these patients. This may also have an effect on the remote ischemia–reperfusion damage and reduce cardiovascular morbidity in this group.

Putting your heart into walking further

Abstract Background Leg exercise training improves maximum walking distance (MWD) in claudicants, but it also causes neutrophil activation and may, as a consequence, elicit damage to the coronary circulation. It was hypothesized that symptomatic improvements induced by exercise programmes result from systemic cardiovascular effects rather than localized changes in the lower limb. The aim of this study was to develop an upper body training programme that would enhance cardiovascular fitness while avoiding potentially damaging inflammatory responses. Methods Sixty-three stable claudicants were recruited; all underwent arm and leg ergometry exercise assessments. Peripheral blood was obtained before and 1 h after exercise. The intensity (median channel of fluorescence; MCF) of neutrophil CD11b expression (as a measure of neutrophil activation) was determined using whole blood flow cytometry. Patients were randomized to an arm (n = 24) or leg (n = 24) training programme structured to achieve identical heart rate changes. Training involved two supervised sessions per week for 6 weeks. Controls undertook no exercise (n = 15). The MWD was determined at the beginning and end of training. Results Arm exercise had no effect on neutrophil expression of CD11b, whereas expression was significantly increased by leg exercise (Table). Arm and leg training increased the maximum work rate from 75 to 100 W (P = 0·004; Wilcoxon test) and there was a concomitant decrease in the submaximal heart rate (arm group 150 to 131 beats min−1; leg group 155 to 136 beats min−1; P = 0·002). These cardiovascular changes were accompanied by an increased MWD (Table). There were no changes in the control group. Conclusion Upper body training can increase walking distance in claudicants without neutrophil activation and maximizing cardiovascular fitness appears to be the key to improving symptoms in these patients.

Effect of Intermittent Pneumatic Foot Compression on Popliteal Artery Haemodynamics

Purpose: the aim was to investigate the effect of intermittent pneumatic foot compression (IPCfoot) on popliteal artery haemodynamics in normal individuals and in patients with intermittent claudication due to peripheral vascular disease (PVD) (Fontaine stage II). Material and methods: popliteal artery volume flow [vFl], pulsatility index [PI], mean velocity [mV], peak systolic [PSV] and end diastolic velocity [EDV], in 25 limbs of 20 normal subjects and 40 limbs of 32 stable claudicants were obtained in the sitting position before, during and within 30 seconds after the application of IPCfoot(applied pressure: 120 mmHg; inflation time: 3 seconds; deflation time: 17 seconds) using colour-flow duplex imaging (CFDI). The reproducibility of flow velocity estimations using CFDI in the horizontal [hor] (recovery) and sitting [sit] positions was evaluated in 20 limbs of normal controls and 20 limbs of claudicants. Results: popliteal artery vFl, mV, PSV and PI measurements were performed with a coefficient of variation (CV) of less than 14.6% among claudicants and of less than 13.3% in normal subjects. EDV is the least reproducible parameter with an overall CV range of 10.2–21.5% in normal controls and 9.1–18.6% in arteriopaths. On application of IPCfootpopliteal artery vFl increased by 111% in the control group (p<0.001) and by 51% in the claudicants (p<0.001). Within 30 seconds of the cessation of pump action flow decreased significantly in both groups (p<0.001), but maintained a significantly higher level than that at baseline (p<0.001, in both groups). The mV, PSV and EDV showed a similar pattern of significant changes. Both in normals and claudicants, the PI decreased with IPCfoot(p<0.001) and increased post-compression; however, it was significantly lower than baseline (p<0.005) within 30 seconds of impulse delivery. Conclusions: current CFDI technology enables a reproducible estimation of popliteal artery flow velocities. IPCfootcan significantly augment arterial calf inflow on an acute basis both in normals and claudicants. The increase of EDV and decrease of PI indicate that attenuation of peripheral resistance to flow is the main mechanism underlying the popliteal artery vFl enhancement on application of IPCfoot. Prospective trials on the long-term effect of IPCfootin the management of patients with PVD are indicated from the results of this study.

Fibrinogen and mortality in chronic critical limb ischaemia.

Plasma fibrinogen predicts cardiovascular events in patients with stable peripheral arterial occlusive disease, but its predictive value in patients with chronic critical limb ischaemia, a condition associated with a high risk of death, is unknown. A prospective cohort study. Determination of fibrinogen and other potential predictors during clinic-based work-up of patients admitted for diagnostic and therapeutic evaluation. A total of 108 patients (72 +/- 10 years, 78 males) with atherosclerotic occlusive disease and critical limb ischaemia (pain at rest and/or trophic lesions) followed up for a median period of 1.6 years). (range: 8 days-5.5 years; 218 patient-years). Total mortality. Forty-five deaths (71% cardiovascular) occurred during the follow-up. Baseline fibrinogen was higher in those who died in the early follow-up period (first 6 months), as were white cell count and serum creatinine, while haematocrit was lower. Plasma fibrinogen values correlated positively with white cell count, and negatively with haematocrit; other cardiovascular prognostic factors did not differ. Only plasma fibrinogen predicted survival independently in multivariate age-corrected Cox regression analysis. Relative risk of death doubled for each standard deviation above the mean and increased with each tertile increase in fibrinogen. Fibrinogen predicted death in these elderly arteriopaths with critical limb ischaemia, particularly those who died in the first months following critical ischaemia. Inflammatory stimuli secondary to severely defective tissue oxygenation and possibly sepsis and necrosis, might have stimulated fibrinogen, an acute-phase reactant, thereby compromising organ perfusion through increased blood viscosity and/or promoting thrombosis.

A Six Year Prospective Study of Fibrinogen and Other Risk Factors Associated with Mortality in Stable Claudicants

A total of 333 patients with stable intermittent claudication at recruitment were followed up for 6 years to determine risk factors associated with subsequent mortality. Cardiovascular diseases were the underlying cause of death in 78% of the 114 patients who died. The strongest independent predictor of death during the follow-up period was the plasma fibrinogen level, an increase of 1 milligram being associated with a nearly two-fold increase in the probability of death within the next 6 years. Age, low ankle/brachial pressure index and a past history of myocardial infarction also increased the probability of death during the study period. The plasma fibrinogen level is a valuable index of those patients with stable intermittent claudication at high risk of early mortality. The results also provide further evidence for the involvement of fibrinogen in the pathogenesis of arterial disease.

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.