Primary Stenting of the Superficial Femoral Artery in Intermittent Claudication Improves Health Related Quality of Life, ABI and Walking Distance: 12 Month Results of a Controlled Randomised Multicentre Trial.

BACKGROUND: Invasive treatment of intermittent claudication (IC) because of severe atherosclerotic stenosis or occlusion in the superficial femoral artery (SFA) is controversial. This prospective randomised trial was performed to assess the impact on health related quality of life (HRQoL) of primary stenting with nitinol self expanding stents compared with best medical treatment alone in patients suffering from stable IC due to SFA disease. METHODS: One hundred patients with stable IC caused by SFA disease from seven Swedish hospitals treated with best medical treatment (BMT) were randomised to either the stent (n = 48) or the control (n = 52) group. Change in HRQoL assessed by the Short Form 36 Health Survey (SF-36) and EuroQoL 5 dimensions (EQ5D) 12 months after treatment was the primary outcome measure. Improvement in the Walking Impairment Questionnaire (WIQ), ankle brachial index (ABI), and walking distance were secondary outcomes. RESULTS: HRQoL improved significantly. In the stent group the following SF-36 domains improved: Physical Function, 19 points (p < .001); Bodily Pain, 14 points (p = .001); General Health, 6 points (p = .019); Vitality, 10 points (p = .004); Physical Component Summary, 6.5 points (p < .001); EQ5D, 0.14 points (p = .008); and WIQ 22 points (p < .001). They were unchanged in the control group. Both ABI (from 0.58 ± 0.11 to 0.86 ± 0.19, p < .001, in the stent group and from 0.63 ± 0.17 to 0.70 ± 0.20, p = .005, in the control group) and walking distance (WD) (from 171 ± 90 meters to 613 ± 381 meters, p < .001, in the stent group and from 209 ± 106 m to 335 ± 321 meters, p = .012, in the control group) improved, and at 12 months both the ABI (p < .001) and the WD (p = .001) were higher in the stent group. CONCLUSIONS: In patients with IC caused by lesions in the SFA, the addition of primary stenting to BMT was associated with significant improvement in HRQoL, ABI, and walking distance after 12 months follow-up compared with BMT alone.

All Cause Chronic Widespread Pain is Common in Patients with Symptomatic Peripheral Arterial Disease and is Associated with Reduced Health Related Quality of Life.

OBJECTIVE: Invasive treatment of peripheral arterial disease (PAD) does not always lead to improvement, as concomitant diseases might affect walking ability and health related quality of life (HRQoL). Patients with chronic widespread pain (CWP) report worse outcome when treated for cancer and rheumatic diseases. The aim of the present study was to evaluate the prevalence of CWP and its potential association with reduced HRQoL in patients treated for PAD. METHOD: This was a longitudinal cohort study conducted between May 2011 and April 2014, including patients with planned invasive treatment of symptomatic PAD at two vascular clinics in Sweden. In 240 patients with planned treatment of PAD, HRQoL and pain distribution were assessed using the Short Form 36 Health Survey (SF-36), EuroQoL 5 dimensions (EQ5D), Walking Impairment Questionnaire (WIQ), and a questionnaire concerning musculoskeletal pain (Epipain manikin) before and 12 months after treatment. HRQoL was compared in patients with no chronic pain (NCP), with chronic regional pain (CRP), and with CWP. The SF-36 subscales PF, VT, and MH, representing important aspects of HRQoL (physical function, vitality, and mental health), were the main outcome measures. RESULTS: Before treatment 22 (10%) patients reported NCP, 133 (61%) CRP, and 64 (29%) CWP. These proportions did not differ between patients with intermittent claudication (IC) and critical limb ischemia (CLI, p = .150). CWP was more common in women than in men (36% vs. 24%, p = .035.) HRQoL improved significantly after treatment in all groups, but was still significantly reduced in CWP patients. CWP predicted worse outcome in HRQoL after treatment. CONCLUSION: CWP is common and is strongly associated with reduced HRQoL in patients with PAD. Treatment led to significant improvement, but patients with CWP still had significantly reduced HRQoL after treatment. CWP measured by a pain manikin should therefore be taken into account when evaluating disease severity, treatment options, and effect of treatment in PAD.

Invasive treatment for infrainguinal claudication has satisfactory 1 year outcome in three out of four patients: a population-based analysis from Swedvasc.

OBJECTIVES: In spite of recommendations advocating conservative best medical treatment, many patients with infrainguinal intermittent claudication (IC) are treated by invasive open and endovascular methods. This study aims to evaluate the incidence and 1-year results of all such treatments during 2009 in Sweden. METHODS: The design was a one-year follow-up through the Swedish Vascular Registry (Swedvasc) of all 775 patients from the Swedish population of 10 million inhabitants in whom 843 invasive infrainguinal procedures (796 index procedures and 47 secondary procedures) were performed for IC in 2009. Index procedures were open surgery in 290 (37%) patients, bilateral in nine cases, giving a total of 299 limbs, endovascular treatment in 447 (58%) patients, bilateral in 10, giving a total of 457 limbs, and hybrid treatment in 38 (5%) patients, bilateral in two cases, giving a total of 40 limbs. Data were analysed both with regard to the number of patients (775) and the number of procedures (843). Clinical outcome was calculated from patient-reported leg function (unchanged, improved, deteriorated) and whether amputation had been necessary or death had occurred. Patent reconstruction at 1 year was also counted as improvement. RESULTS: Improvement at 1 year was seen in 567 (73.2%) patients, (225 [77.6%] in the open surgery group, 320 [71.6%] in the endovascular treatment group, and 22 [57.9%] in the hybrid treatment group). No significant difference was found between the open surgery and endovascular treatment groups comprising 737/775 patients (p = .350). Hybrid treatment gave significantly worse results (p = .046). Fifty-seven (7.3%) patients reported unchanged limb function and 32 (4.1%) patients reported deterioration. Within 30 days two patients died and one patient underwent amputation. Within 1 year 10 patients underwent 11 amputations: five (1.7%) in the open surgery group, three (0.6%) in the endovascular treatment group, and two (7.5%) in the hybrid treatment group; one underwent bilateral amputation (p = .07). Twenty-two patients died: 10 (3.4%) in the open surgery group, 12 (2.7%) in the endovascular treatment group and none in the hybrid treatment group (p = .465). CONCLUSIONS: Reported improvement at 1 year was 73.2% in patients invasively treated for infrainguinal IC. Patients reporting an unchanged or deteriorated clinical state are a considerable clinical challenge. Further studies to determine whether or not invasive treatment of infrainguinal IC is appropriate are justified.

Platelet adhesion in polytetrafluoroethylene (PTFE) vascular grafts in vivo and the influence of increased intramuscular pressure--an experimental model.

Thrombogenicity of graft material is involved in early graft failure in small diameter grafts. The frequently seen postoperative swelling of the leg after distal revascularization may cause an increased intramuscular pressure and early graft failure. Pairs of 4 mm polytetrafluoroethylene (PTFE) grafts were implanted. Autologous platelets were labeled with 111In-oxine. Platelet adhesiveness onto the grafts were analyzed from gamma camera images. Intramuscular pressures were measured with wick technique. Blood flow was measured. One graft served as control the other as test graft. Ninety minutes after declamping the i.m. pressure was increased in the test-leg to 30 mmHg, and later to 60 mmHg. In the control-graft platelet uptake increased to a maximum 60 min after declamping. Blood flow and i.m. pressure remained uneffected. The test-grafts were initially similar but when i.m. pressure was increased to 30 mmHg activity in the grafts increased significantly. Blood flow decreased with 12% of initial flow. When i.m. pressure was raised to 60 mmHg platelet uptake continued to increase. An increased intramuscular pressure of 30 mmHg or more significantly increase the amount of platelets adhering onto PTFE grafts, emphasizing the need for measuring intramuscular pressures after lower limb vascular revascularizations.

Intramuscular pressure, blood flow, and skeletal muscle metabolism in patients with venous claudication.

Nine patients with chronic iliac vein obstruction and venous claudication were investigated. Intramuscular pressure was measured in the anterior tibial and the deep posterior compartments in both legs at rest and during exercise. The pressures were significantly higher in the leg with iliac vein obstruction (39 +/- 10 mm Hg) than in the contralateral leg (26 +/- 12 mm Hg) at rest as well as during exercise (60 +/- 16 mm Hg and 41 +/- 15 mm Hg, respectively) in the deep posterior compartment. Similar changes were observed in the anterior tibial compartment. Muscle water content was higher (P less than 0.01) in the obstructed leg and contributes to the explanation for the high intramuscular pressure in this leg. Muscle blood flow, adenosine triphosphate, phosphocreatine, and lactate were determined in the gastrocnemius muscles at rest and at exercise. Muscle blood flow, measured with the 133xenon clearance technique, was lower in the obstructed leg (17.5 ml/min, 100 gm) than in the control leg (28.1 ml/min, 100 gm) during exercise. Lactate increased more (P less than 0.05) in the obstructed leg. It is suggested that pain in venous claudication is caused by the high intramuscular pressure, and therefore fasciotomy may be useful in the treatment of this disorder.

Hypercholesterolemia and early restenosis after carotid endarterectomy.

Cellular proliferation in response to endothelial injury has been examined extensively in experimental animals. Under certain conditions (e.g., hypercholesterolemia and hypertension), this response can be exaggerated and develop into lesions that resemble early atherosclerosis. The injury caused by endarterectomy in human beings and the repair of the arterial wall that ensues may be analogous to the animal models. Presumably, those patients with an exaggerated proliferative response manifest myointimal hyperplasia and recurrent stenosis. To determine potential causes of recurrent stenosis after carotid endarterectomy, we studied 31 patients with early restenosis (group I), 35 patients with later restenosis (group II), and compared them with a control group of 100 consecutive patients who underwent uncomplicated carotid endarterectomy (group III). The known risk factors for atherosclerosis were analyzed. There was no significant difference in the male-to-female ratio, number of cigarettes smoked, or incidence of diabetes mellitus. However, the serum cholesterol level for group I was 282 +/- 57 mg/dl (p less than 0.001 versus controls) while the serum cholesterol level in group II was not significantly elevated over that of the control group. Both groups I and II had a higher incidence of hypertension (p less than 0.005 for both versus controls). There were no differences in the severity of hypertension. The data suggest that hypercholesterolemia has a strong association with early restenosis after carotid endarterectomy but not with late recurrent disease and that hypertension, even when treated, may be associated with both early and late recurrent stenosis.

Prostacyclin production in regions of arterial stenosis.

The effect of abnormal flow dynamics on prostacyclin (PGI2) production by intact endothelium is unknown. To investigate this we studied the effects of graded stenoses on vessel wall PGI2 production in dogs (n = 8) whose femoral and carotid arteries (n = 32) were narrowed by machine-milled clips, producing 1.0 cm segmental stenoses of 25%, 50%, 75%, and 90% diameter reduction. Three dogs were injected with Indium 111-labeled platelets and 12 vessels were scanned for platelet deposition. All stenotic vessels were excised at 6 weeks for histologic study (hematoxylin-eosin section and immunohistochemistry for factor VIII) and PGI2 radioimmunoassay (as the metabolite 6-keto PGF1 alpha). All vessels remained patent with no thrombus formation in any segment. Vessel imaging in platelet-labeled animals showed no significant deposition. Histologic analysis demonstrated an intact endothelial surface in the stenotic segments, confirmed by the demonstration of factor VIII production by these cells. PGI2 production (per unit surface area) by the arterial segments with greater than or equal to 50% stenosis markedly exceeded the PGI2 production by the normal proximal and distal segments (p less than 0.0002) and showed further significantly increased production with increasing degrees of stenosis (p less than 0.00001). The data indicate increased PGI2 production by normal endothelium in regions of arterial stenosis. The mechanism of this increase is unknown, but this endothelial "turn on" effect may serve to inhibit deposition of platelets and thrombus formation in the presence of disordered flow patterns.

Supraclavicular radical scalenectomy and transaxillary first rib resection for the thoracic outlet syndrome. A combined approach.

Transaxillary resection of the first rib alone was performed 97 times to relieve symptoms of irritation of the brachial plexus. Persistent or recurrent symptoms occurred in a fifth of the patients (7 and 13 patients, respectively), and necessitated reoperation using the supraclavicular approach. In all patients, at least one anomaly or acquired deformity was found that could not have been identified or safely removed by the original transaxillary approach alone. Subsequently, 94 combined operations, including supraclavicular radical scalenectomy with neurolysis of the brachial plexus and transaxillary resection of the first rib, were performed for irritation of the brachial plexus. The improved results using the combined procedure has led us to recommend it for the majority of symptomatic patients with irritation of the brachial plexus. The combined approach allows precise assessment of the thoracic outlet anatomy, facilitates first and cervical rib resection, and permits removal of any additional congenital or acquired lesions. It is associated with a low failure rate and results in few postoperative complications. However, the transaxillary approach alone may be suited for the patient with localized lower plexus symptomatology, keeping in mind the risk of recurrent symptoms associated with this technique.

Computerized tomographic assessment of graft incorporation after aortic reconstruction.

Computerized tomographic scanning is being used with increasing frequency for the detection of abdominal aortic prosthetic complications. Although computerized tomography remains a very precise method for direct imaging of the retroperitoneal space, the interpretation of a postoperative computerized tomographic scan is limited by the absence of any information on the normal appearance of the routine uncomplicated aortic graft. To study the normal tissue incorporation of aortic grafts, 29 patients were evaluated with periodic postoperative computerized tomographic scans. Seventeen patients had aortoiliac occlusive disease and 12 had aneurysmal disease. No patients who had reoperation were included and all patients had a normal postoperative course. Computerized tomographic scans were obtained in the early (mean 7 days), intermediate (mean 48 days), and late (mean 102 days) postoperative periods. A variable amount of perigraft hematoma was always present on the initial computerized tomographic scan. Perigraft air was seen in only four patients in the early study. Graft incorporation appeared complete in these patients by 48 days, although minimal hematoma persisted in one patient. This study provides baseline data on the appearance and timing of aortic graft incorporation which should facilitate subsequent computerized tomographic detection of aortic graft complications.

Polymorphonuclear leucocytes increase reperfusion injury in skeletal muscle.

OBJECTIVE: To study the effect of polymorphonuclear leucocytes (PMNLs) on reperfusion injury in rabbit skeletal muscle and to evaluate the role of oxygen-derived free radicals in PMNL-mediated reperfusion injury. EXPERIMENTAL DESIGN: An isolated rabbit limb perfusion model. Amputated hindlimbs were subjected to 4 hours of ischaemia followed by 2 hours of reperfusion with oxygenated Krebs' buffer. SETTING: Department of experimental surgery. ANIMALS: 14 rabbits. INTERVENTIONS: In group I (n = 8), one limb from each animal was reperfused with PMNL-supplemented buffer while the other limb was reperfused with cell-free buffer (control). In group II (n = 6), SOD and catalase were added to the limb reperfused with PMNL-supplemented buffer while the other limb was reperfused with cell-free buffer without SOD and catalase (control). MEASURES: PMNL accumulation as myeloperoxidase (MPO) activity, muscle necrosis as uptake of [Tc99]methylenediphosphonate (MDP), and oedema as increase in muscle water content (MWC). Electron microscopy was performed for histological demonstration of reperfusion injury. RESULTS: Addition of PMNLs increased MPO activity (p < 0.05) and MDP uptake (p < 0.05) but did not affect MWC. SOD and catalase treatment of limbs perfused with PMNLs prevented the increase in MPO activity (p < 0.05) and reduced MDP uptake (p < 0.05) and MWC (p < 0.05). PMNLs aggravated histological changes seen after reperfusion. CONCLUSIONS: Reperfusion injury in skeletal muscle is, at least partially, mediated by PMNLs. Free radical scavengers reduce PMNL-dependent injury and prevent PMNL accumulation suggesting that oxygen-derived free radicals are mediators of PMNL-dependent injury and/or engaged in the interaction between PMNLs and the microvascular endothelium.

Distal bypass with the saphenous vein in situ. Technical aspects and early results.

The in situ saphenous vein graft has theoretical advantages, e.g. preservation of vasa vasorum and normally functioning endothelium, over the reversed vein graft and has gained popularity in recent years. Forty-three patients underwent 45 distal in situ saphenous vein bypasses for limb salvage during a 15-month period. The Hall valve stripper was found to be superior to the Mill valvulotome for valve incision. Intraarterial digital subtraction angiography (DSA) was a useful tool for perioperative anastomosis and graft evaluation. The incidence of early graft failure, 8/45 (18%), was mostly due to identifiable causes, mainly small caliber veins (less than 2.5 mm diameter). The cumulative patency rate of 77% remained stable during the follow-up period of 15 months. Perioperative mortality was zero. The main technical advantage with the in situ method is the reduced size disparity at the anastomotic sites. The in situ technique allowed the successful use of veins as small as 2.5 mm in diameter which resulted in a vein utilization rate of 95%. This rendered long distal bypasses possible in patients who could not have been reconstructed with the reversed vein technique.

Intramuscular pressure, venous function and muscle blood flow in patients with lymphedema of the leg.

Intramuscular pressure, muscle blood flow and venous emptying was studied in seven patients with unilateral lymphedema of the leg. Intramuscular pressure was measured with the wick technique. Muscle blood flow was assessed by means of the 133Xenon clearance technique. Venous emptying was studied with strain gauge technique. Intramuscular pressure in the anterior tibial compartment of the edematous leg was 30 +/- 14 mmHg at rest, rising to 49 +/- 16 mmHg during exercise (p less than 0.05). In the healthy leg the pressure rose from 16 +/- 8 mmHg at rest to 28 +/- 6 mmHg during exercise (p less than 0.05). In the deep posterior compartment similar pressure values were obtained. Muscle blood flow during exercise was significantly higher (p less than 0.05) in the healthy leg, 32.4 +/- 6.8 ml X min-1 X (100 g)-1 than in the edematous leg, 29.9 +/- 4.8 ml X min-1 X (100 g)-1. Venous emptying was significantly lower (p less than 0.05) in the diseased leg, 44.7 +/- 18.7 ml X min-1 X (100 g)-1 than in the healthy leg, 61.4 +/- 18,9 ml X min-1 X (100 g)-1. Thus, lymphatic obstruction of the leg causes edema which leads to an increased intramuscular pressure and a decreased muscle blood flow and venous emptying.

Gender differences in outcome after stent treatment of lesions in the femoropopliteal segment.

BACKGROUND AND AIMS: Although endovascular stent treatment is increasingly used in infrainguinal atherosclerotic occlusive disease, outcome with focus on gender differences has not been reported in detail. MATERIAL AND METHODS: One hundred and twelve consecutive patients (67 [60%]) women, undergoing endovascular nitinol stent treatment of atherosclerotic lesions in the femoropopliteal segment were analysed concerning improvement in ankle brachial index (ABI), reinterventions, complications, amputation and survival rates up to 12 months after intervention. Risk factors for amputation and death were analyzed with logistic regression. RESULTS: At presentation, women showed critical limb ischemia (CLI) more often than men (87% vs. 58 %; P = 0.001). After 12 months ABI had improved (from 0.40 ± 0.26 at baseline to 0.86 ± 0.22 after 12 months, P < 0.001), but 16 patients (15%) had been amputated and 27 patients (24 %) had died. After adjustment for age, diabetes mellitus and smoking, female gender was an independent risk factor for amputation (OR 9.0; 95% CI 1.1-76.5; P = 0.045). CONCLUSIONS: Stent treatment of lesions in the femoropopliteal segment had favourable effects on ABI and limb salvage. Treated women more often had CLI and ran a higher risk for amputation within 12 months than men. This might reflect failure of clinicians to adequately appreciate symptoms of atherosclerotic leg artery disease in women.

Fluoropolymer-coated dacron versus PTFE grafts for femorofemoral crossover bypass: randomised trial.

OBJECTIVES: To investigate whether patency of a thin walled 8 mm fluoropassivated Dacron graft was similar to that of a standard 8mm PTFE graft for femorofemoral crossover bypass surgery. DESIGN: A randomised multicentre clinical trial comparing two vascular grafts with participation of 10 departments of vascular surgery in Denmark, Sweden and Norway. PATIENTS AND METHODS: 198 patients were randomised to PTFE (n=107) or fluoropolymer-coated Dacron grafts (n=91), 63% underwent surgery for claudication, 27% for ischaemic rest pain and 10% for tissue loss. The median follow-up time was 24 months (IQR 19-26 months). RESULTS: The primary patency rate of the two grafts was similar (log rank test: p=0.35). The primary patency rates (95% CI) for coated Dacron and PTFE grafts were 92% (86-98) and 94% (89-99) at 12 months and 87% (74-95) and 93% (87-99) at 24 months, respectively. CONCLUSION: In patients with unilateral iliac artery disease not amenable to angioplasty, the femoral-femoral bypass is durable and effective. No difference in patency was found between the two graft materials (fluoropolymer coated Dacron and PTFE).

Allopurinol--a free radical scavenger--reduces reperfusion injury in skeletal muscle.

Reperfusion of ischaemic skeletal muscle may lead to increased vascular permeability, oedema and ultimately muscle necrosis. Oxygen-derived free radicals have been suggested as aetiological factors in reperfusion injury. Amputated rabbit hindlimbs were subjected to 4 h of ischaemia followed by 2 h or reperfusion with Krebs' buffer. One limb from each animal was reperfused with oxygen-saturated buffer (reoxygenated limb) while the other limb was reperfused with nitrogen-saturated buffer (non-reoxygenated limb). Six animals received allopurinol orally 2 days prior to the experiment and ten animals received no treatment. The energy charge dropped from 0.90 to 0.54 during ischaemia and increased to 0.82 after reperfusion with oxygenated perfusate. Oedema was determined by limb weight and water content in muscle biopsies and muscle injury was assessed by uptake of [Tc99]methylenediphosphonate ([Tc99]MDP). The results were expressed in ratios, between the reoxygenated and nonreoxygenated limb. Without allopurinol treatment, the increase in water content and limb weight in reoxygenated limbs exceeded (p less than 0.05) non-reoxygenated limbs (ratios = 1.73 and 1.89, respectively). Allopurinol treatment significantly reduced (p less than 0.05 and p less than 0.02, respectively) the increase in water content and limb weight (ratios = 0.54 and 1.01, respectively). Without treatment, [Tc99]MDP-uptake was greater (p less than 0.05) in reoxygenated limbs than in non-reoxygenated limbs (ratio = 1.60). Allopurinol treatment significantly reduced (p less than 0.002) [Tc99]MDP-uptake in reoxygenated limbs (ratio = 0.80). These results demonstrate that additional injury to ischaemic skeletal muscle occurs during reperfusion with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of mannitol on reperfusion injury and postischaemic compartment pressure in skeletal muscle.

Mannitol has previously been shown to reduce skeletal muscle reperfusion injury and postischaemic compartment pressure. The present study was designed to evaluate whether these effects result from hyperosmolarity or free radical scavenging. A rabbit hindlimb perfusion model was used to compare the effects of mannitol (n = 6), glucose (n = 6)--an isomer of mannitol without scavenging effect--and fasciotomy (n = 6) on oedema, compartment pressure, energy charge, and muscle injury after 4 hours of ischaemia and 2 hours of reperfusion. One limb from each animal received treatment, while the other limb served as an untreated control. Mannitol and glucose reduced (p < 0.05) muscle water content and decreased (p < 0.01) the compartment pressure. Fasciotomy had no effect on muscle water content but normalised compartment pressure. The increase in energy charge following reperfusion was improved (p < 0.05) and uptake of [Tc99]methylenediphosphonate--an indicator of muscle injury--was reduced (p < 0.05) by mannitol only. In conclusion, mannitol reduces postischaemic oedema mainly by its hyperosmolar property whereas restitution of energy production and reduction of muscle necrosis seem to be an effect of free radical scavenging. The compartment pressure is reduced by hyperosmolarity and free radical scavenging.