Factors Affecting Patency of Subintimal Infrainguinal Angioplasty in Patients with Critical Lower Limb Ischemia

BACKGROUND: Because subintimal angioplasty (SA) is a technique that can achieve recanalization of long arterial occlusions, it is considered an alternative to lower limb bypass operations. The aim of this prospective study was to identify the risk factors that affect patency of SA in patients suffering from critical limb ischemia (CLI). METHODS AND RESULTS: 51 consecutive infrainguinal SA were done in 46 patients suffered from CLI. The patients were followed-up with regular duplex scans up to 12 months post-intervention. Sex, atherosclerosis risk factors, and some technical details of the procedure (number of patent run-off vessels after the procedure, length and re-entry point of angioplasty) were examined as potential risk factors of patency, using survival analysis statistical techniques. The overall patency rate at 12 months post-intervention was 50%. According to Cox-regression analysis, the factors that affect patency were the number of run-off vessels and the length of occlusion. Patients with two or three run-off vessels had a hazard of occlusion of 0.30 (P = .027) compared to those who had one run-off vessel. The 12-months patency in patients with more than one run-off vessels was 81% vs. 25% in patients with one run-off vessel. Regarding the length of angioplasty, the hazard of reocclusion was 1.02 for every centimeter of occlusion (P = .049). CONCLUSIONS: The number of patent run-off crural vessels after the angioplasty and the length of occlusion are significant risk factors for reocclusion of infrainguinal SA in patients with CLI. Trying to recanalize more than one run-off vessels could raise the SA patency.     

A prospective comparison of intra-arterial digital subtraction and conventional angiography prior to lower extremity revascularization

Prior to lower extremity revascularization, patients underwent CA or IADSA as the only radiologic study. A total of 30 patients were entered into each group and subsequently underwent a reconstructive procedure. Each study in the CA group was deemed accurate at the time of surgery, in assessing suitability of vessels for anastomosis. Of the patients undergoing surgery based exclusively on IADSA, 5 were noted in whom this examination provided insufficient detail or were misleading, resulting in attempted reconstructions at inappropriate sites. These results were statistically significant and indicate that IADSA should not be used as the only imaging technique in the preoperative evaluation of lower extremity vascular disease. IADSA is most useful as a complementary technique to CA and should be performed during the same examination when the latter fails to identify distal runoff vessels. In the majority of cases, CA alone will provide sufficient information and should be used as the initial contrast study.     

Critical limb ischaemia as a main cause of death in patients with end-stage renal disease: a single-centre study.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a high overall mortality rate, particularly due to cardiovascular morbidity. In an era of decline in cardiovascular diseases and early cardiovascular intervention, non-cardiac diseases seem to have a larger impact on overall mortality. METHODS: From 1997 to 2003, all incident haemodialysis patients in a single centre were enrolled in this prospective study. Those with clinical signs of vascular disease were examined by coronary or peripheral angiographies. Physicians took the patients' medical histories, examined them and followed them up until the end of the study or death. Causes of death were defined by the physicians. RESULTS: In all, 322 patients were enrolled in the study, 38% of whom were diabetic. At the start of dialysis treatment, 38% had coronary artery disease (CAD), defined as >50% stenosis of at least one coronary artery or as definite myocardial infarction, and 14% had critical ischaemia of at least one limb (CLI). In all patients with foot lesions, CLI was defined angiographically, as evidenced by stenosis or rarefication of distal vessels in the legs. Patients who died (n = 121) [due to cardiac causes (n = 25), complications of CLI (n = 22), stroke (n = 10), cachexia following a long-standing, non-malignant disease (n = 6), malignancy (n = 24), infection not related to CLI (n = 18) and other causes (n = 16)] were older (71+/-10 vs 65+/-13 years), more often male [74/121 (61%)] and often diabetic [56/121 (46%)]. CAD was documented in 82/121 (68%). Five-year survivals in patients with no risk and diabetes without CAD or CLI, CAD and CLI were 74%, 73%, 50% and 10%, respectively. Age, CLI and smoking habits independently increased the risk of death (hazard ratios: 1.052, 4.921 and 2.292, respectively). CONCLUSIONS: These results indicate that CLI with associated complications is not only an indicator of high mortality in patients with ESRD, but is also one of the main causes of death.     

Managing risk factors for atherosclerosis in critical limb ischaemia.

OBJECTIVE: To review the best medical management of critical limb ischaemia (CLI). METHODS: Published studies dealing with CLI and risk factors were searched for via PUBMED. FINDINGS AND CONCLUSIONS: Patients with critical limb ischaemia (CLI) have a one and ten year mortality of approximately 20% and 75% respectively. Risk factors for the development of peripheral atherosclerosis are the same as for coronary and cerebrovascular atherosclerosis namely diabetes mellitus, hyperlipidaemia, arterial hypertension, and smoking. As there are few studies of risk factor for peripheral arterial occlusive disease (PAOD), treatment recommendations are often based on studies in patients with coronary or cerebrovascular atherosclerosis. While waiting for specific studies, CLI patients should be treated according to current guidelines for other atherosclerotic patients.     

'Pole test' measurements in critical leg ischaemia.

BACKGROUND: For the quantification of critical limb ischaemia (CLI) most vascular surgery units use sphygmo-manometric and transcutaneous oxygen pressure (TcPO2) measurements. However, measurements obtained by cuff-manometry can be overestimated especially in diabetic patients because of medial calcification that makes leg arteries less compressible. TcPO2 measurements present a considerable overlap in the values obtained for patients with different degrees of ischaemia and its reproducibility has been questioned. Arterial wall stiffness has less influence on the pole test, based on hydrostatic pressure derived by leg elevation, and this test seems to provide a reliable index of CLI. OBJECTIVE: The objective of this study was to evaluate the pole pressure test for detection of critical lower limb ischaemia, correlating results with cuff-manometry and transcutaneous oxygen pressure. DESIGN: University hospital-prospective study. MATERIALS AND METHODS: Seventy-four patients (83 legs) with rest pain or gangrene were evaluated by four methods: pole test, cuff-manometry, TcPO2 and arteriography. CLI was present if the following criteria were met: (a) important arteriographic lesions+rest pain with an ankle systolic pressure (ASP) < or = 40 mmHg and/or a TcPO2 < or = 30 mmHg, or (b) important arteriographic lesions+tissue loss with an ASP < or = 60 mmHg and/or a TcPO2 < or = 40 mmHg. Fifty-seven lower limbs met the criteria for CLI. RESULTS: Measurements obtained by cuff-manometry were significantly higher to those obtained by pole test (mean pressure difference: 40 mmHg, p<0.001). The difference between the two methods remained statistically significant for both diabetics (50.73, p<0.001) and non-diabetics (31.46, p<0.001). Mean TcPO2 value was 15.51 mmHg and there was no important difference between patients with and without diabetes. Overall, there was a correlation between sphygmomanometry and pole test (r = 0.481). The correlation persisted for patients without diabetes (r = 0.581), but was not evident in patients with diabetes. Correlation between pole test and TcPO2 was observed only for patients with diabetes (r = 0.444). There was no correlation between cuff-manometry and TcPO2. The pole test offered an accuracy of 88% for the detection of CLI. The sensitivity of this test was 95% and the specificity 73%.     

Intra-arterial digital subtraction angiography in the evaluation of peripheral vascular trauma.

The role of intra-arterial digital subtraction angiography (IADSA) in the evaluation of extremity trauma has not been clearly established. Several potential advantages would make IADSA a preferable study to conventional angiography (CA). This retrospective study analyzed 104 major peripheral arteries with suspected injury. Multiplane IADSA studies were compared with conventional angiography of the same vessel in 97 patients. The arteriograms were evaluated by a physician and a radiologist in a double-blinded fashion. IADSA correlated well with CA. Similar findings comparing both studies were noted in 101 of 104 angiograms (97%) (p less than 0.001) in review by the radiologist and in 100 of 104 (96%) (p less than 0.001) by the surgeon. Only one injury confirmed at surgery was not seen on IADSA; this study was read as equivocal by both examiners. These data confirm that IADSA is a reliable and reasonable study for the evaluation of patients with suspected peripheral arterial injury.     

Vascular training in the U.K.: femorodistal bypass, an index procedure?

OBJECTIVES: femorodistal bypass operation is one of three index procedures for vascular training in the U.K. Our aim is to determine the suitability of femorodistal bypass to be considered as an index procedure in the era of increasing utilisation of percutaneous transluminal angioplasty (PTA). DESIGN: a retrospective analysis of prospectively collected data. PATIENTS AND METHODS: a total of 526 patients with 608 chronic critically ischaemic limbs admitted to the vascular unit, at the Royal United Hospital, Bath, between January 1994 and December 1999 was included in the study. RESULTS: revascularisation either by PTA, bypass surgery or a combination of both was attempted in 524 limbs (86%). Crural procedures were carried out on 71 limbs (14% of revascularised limbs). Primary crural procedures included 34 PTAs as a sole treatment (48%), and 37 femorodistal bypass operations (52%). CONCLUSIONS: during a 6-year period only 37 primary femorodistal bypass operations were performed in a unit which aggressively treats CLI. PTA is the initial step and increasingly the sole treatment for critical limb ischaemia (CLI), including distal lesions. We question the rationale of including an uncommon operation as a vascular training index procedure.     

Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study.

BACKGROUND AND AIMS: Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia in one randomized clinical study. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with stable critical limb ischaemia (CLI). Design: A prospective, combined-centre pilot study. MATERIAL: Eight patients with CLI of the lower extremities, and without any other treatment options. METHODS: Bone marrow cells were harvested from the patient's iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAS) and several non-invasive circulatory physiological tests. RESULTS: There were no complications from the procedures. Two patients were amputated two months after cell injection. Five patients reported pain relief after four months. Five patients could be evaluated at eight months. According to VAS and physiological tests, they were all either stable or showed improvement. CONCLUSION: This method seems to be a safe option for treating patients with CLI. Inclusion of patients took a long time, mainly because many patients with CLI are offered endovascular treatment in our institution. While symptomatic improvement was found in individual patients, larger trials are required to investigate efficacy. This will probably require multi-centre participation.     

Microtibial embolectomy.

BACKGROUND: microtibial embolectomy is an important technique in cases of limb threatening acute arterial occlusion affecting native crural and pedal vessels. It is particularly useful when thrombolysis is contraindicated or ineffective as in "trash foot". METHODS: in order to evaluate the efficacy of this technique, a retrospective case note review was carried out for patients undergoing microtibial embolectomy from 1990 to 1999. Data collected included the causes and degree of ischaemia, additional procedures required, vessel patency, limb salvage and complications encountered. RESULTS: twenty-two limbs underwent exploration of the crural/pedal vessels with ankle level arteriotomies under local anaesthetic in 12 cases, general anaesthetic in nine and epidural in one. The causes of ischaemia were cardiac emboli (8), "trash foot" (7), emboli from aortic and popliteal aneurysms (3) and thrombotic occlusion of crural vessels (4). The vessel patency rate was 69% and limb salvage rate 62% (13/21) up to 5-years follow-up. Six of the seven cases with "trash foot" were salvaged while one required an amputation at 3-months post-operatively. The 30-day mortality was 22% (5/22). CONCLUSIONS: microtibial embolectomy is effective in acute occlusion of the crural/pedal arteries including cases of "trash foot", offering limb salvage to a worthwhile proportion of cases.     

Lower limb occlusive arterial disease in the North of England: workload and development of management guidelines. The Northern Regional Vascular Surgeons.

BACKGROUND: in 1997 the vascular surgeons across the North of England commenced a study to examine various aspects of the management of lower limb occlusive arterial disease (LLOAD). Two aspects of this work were to assess workloads between hospitals and develop guideline parameters for managing intermittent claudication (IC) and critical limb ischaemia (CLI). The guidelines were to be developed, tested and modified by this study. METHOD: prospective inclusion of all patients admitted for investigation of LLOAD to nine hospitals by 19 surgeons over a period of 12 months. RESULTS: the hospitals admitted an average of 106 legs per 100 000 population (range 53-149) with LLOAD. Legs with IC (n=1351) were revascularised slightly less frequently than predicted (actual 76%, guideline 80%) and radiological treatment was used more frequently than predicted (radiology/surgery, actual 69/32%, guideline 40/60%). For limbs with CLI, revascularisation was undertaken more often (actual 70%, guideline 60%) and radiological intervention used more frequently (radiology/surgery, actual 45/58%, guideline 35/65%) than anticipated. Primary amputation, overall mortality and limb salvage were better than the predicted guidelines. CONCLUSION: large variations in workloads and clinical practice were observed between hospitals for the management of LLOAD. Developing guidelines for the management of limbs with IC was not considered appropriate, whereas suitable guidelines for legs with CLI were developed, tested and modified.     

Crural or pedal artery revascularisation for limb salvage: is it justified?

With the ageing of population, the incidence of limb-threatening ischemia increases. In chronic critical limb ischemia, peripheral arterial occlusive disease almost always involves infrainguinal and infragenicular vessels. Fortunately, recent advances in vascular surgery made arterial reconstruction of crural and pedal vessels possible. Should crural or pedal bypass surgery be offered to these frail, polyvascular patients, or is primary amputation a preferable treatment option in case of advanced limb-threatening ischemia? In order to answer this controversial question, the author analysed recent literature data on the feasibility and durability of infrapopliteal bypasses. The quality of life was also considered as an outcome measure. Finally, the cost-effectiveness of both treatment modalities (limb-saving distal bypass versus primary amputation) was assessed.     

A 1 year prospective study of management and outcome of patients presenting with critical lower limb ischaemia.

OBJECTIVES: to determine management of patients with critical lower limb ischaemia (CLI) from first presentation to investigation and treatment. DESIGN: prospective study of critical ischaemia patients. METHODS: one-year prospective survey (May 2000-May 2001). Follow-up 3-15 months. RESULTS: some 873 arterial cases presented, 134 patients had CLI. Of the latter 49% were men, 30% diabetic, the median age was 81 years. Only 15 (24%) of 62 cases were referred to outpatients as urgent. Patients waited a median of 25 days (range 1-100) to be seen in outpatients, and had symptoms for a median of 8 weeks. Treatment was conservative for 70 patients, and 11 primary amputations, six secondary amputations, and 62 revascularisation procedures (34 operative, 28 percutaneous transluminal angioplasty) were performed. At follow-up (3-15 months, median 9 months), rates of major amputation and death were 12 and 27% respectively. Significantly more diabetics underwent major amputation (p < 0.02) than non diabetics. Patients presenting with ulceration or gangrene were at greater risk of death than those with rest pain alone (p < 0.01). CONCLUSION: patients with CLI often have symptoms for many weeks before being seen by a specialist, and 76% are referred as non-urgent cases. This compares with patients with suspected malignant disease in the U.K. who are required to be seen within 2 weeks.     

Ergebnisse der peripheren Bypasschirurgie bei Patienten mit kritischer Extremitätenischämie

Aim

The outcomes of patients with critical limb ischemia (CLI) who underwent lower extremity bypass surgery were analyzed based on the data in the CRITISCH registry with respect to the localization of the distal anastomosis and type of bypass material.

Patients and methods

In total 284 patients with a lower extremity bypass (group 1: 75 patients with bypass above the knee, group 2: 80 patients with bypass below the knee and group 3: 129 patients with crural or pedal bypass) were included in this study. The graft material included 159 autologous saphenous vein grafts and 125 prosthetic grafts.

Results

There were no perioperative complications in 191 out of the 284 patients (67.3?%) and in 236 out of the 284 (83.1?%) patients the bypass remained open at discharge from hospital. An uneventful postoperative course was documented in 76?% of the patients in group 1, 62.5?% in group 2 and 65.1?% in group 3. The amputation-free survival at 1 year was 86?% in group 1, 65?% in group 2 and 69?% in group 3. In patients with a bypass above the knee prosthetic grafts were at least not inferior to vein grafts (amputation-free survival at 1 year: prosthetic bypasses 92?%, saphenous vein grafts 71?%, p?=?0.147), while in the group with a crural or pedal bypass, vein grafts showed a better amputation-free survival at 1 year (76?%) compared with prosthetic bypasses (56?%, p?=?0.105). Patients with a PIII CLI risk score ≤?3 exhibited a better amputation-free survival at 1 year of 78?% compared to patients with PIII CLI risk scores 4–7 with 69?% (p?=?0.053). The same applied to patients with Rutherford stage 4 versus Rutherford stage 6 CLI.

Conclusions

In patients with CLI and a bypass above the knee, vein grafts provide no benefits for at least 1 year follow-up when compared with prosthetic grafts. But in more distal anastomoses vein grafts should be preferred.

     

Chapter II: Diagnostic methods

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.     

Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity.

OBJECTIVES: Arteriographic lesions of diabetic subjects with critical limb ischemia (CLI) and ischemic foot ulcer were reviewed retrospectively, to provide new criteria for stratification of these patients on the basis of their vascular involvement. PATIENTS: In 417 consecutive CLI diabetic subjects with ischemic foot ulcer undergoing lower limb angiography, lesions were defined as stenosis or occlusion, localization, and length (<5 cm, 5-10 cm, >10 cm). In a subgroup of 389 subjects, foot arteries also were evaluated. Patients then were categorized into 7 classes of progressive vascular involvement based on angiographic findings. RESULTS: Of the 2893 found lesions (55% occlusions) 1% were in the iliac arteries, whereas 74% were in below-the-knee (BTK) arteries. Sixty-six % of all BTK lesions were occlusions, and 50% were occlusions >10 cm (p<0.001 vs proximal segments). Occlusions of all BTK were present in 28% of patients, although there was patency of at least one foot artery in 55% of patients. The morphologic Class 4 (two arteries occluded and multiple stenoses of tibial/peroneal and/or femoral/popliteal vessels) was the most common (36%). An inverse correlation between morphologic class and TcPO2 was observed (r=-0.187, p=0.003). CONCLUSIONS: In CLI diabetic subjects with ischemic foot ulcer, the vascular involvement is extremely diffuse and particularly severe in tibial arteries, with high prevalence of long occlusions. A new morphologic categorization of these patients is proposed.     

VEGF and VEGF Receptor Expression in Human Chronic Critical Limb Ischaemia

OBJECTIVE: This study quantified endogenous VEGF and VEGF receptor expression in limbs of patients with chronic critical limb ischaemia (CLI). METHODS: Skin and muscle biopsies were obtained from the legs of 25 patients undergoing limb amputation for CLI. Samples were obtained at the amputation level (thigh or calf) and, distally, from the foot and in the vicinity of ischaemic ulcers and gangrene. Control biopsies were obtained from patients undergoing amputation for non-arterial reasons or knee arthroplasty (n=7). VEGF protein levels in tissue lysates were measured by ELISA, and VEGF and KDR mRNA levels were determined using quantitative PCR. RESULTS: At the amputation level, VEGF protein and VEGF and KDR mRNA levels in CLI limbs were similar to those in controls. In the foot VEGF mRNA in skin (P=0.005) and VEGF protein levels in muscle (P=0.02) were elevated compared to levels in a proximal biopsy from the same limb. VEGF and KDR mRNA levels in the vicinity of gangrene/ulcers (VEGF P=0.01, KDR P=0.03) also were elevated. CONCLUSIONS: VEGF expression is not deficient in CLI. Indeed, it is elevated at distal sites in the ischaemic limb. These findings question the rationale for VEGF supplementation in CLI.     

Comparison of treatment plans for peripheral arterial disease made with multi-station contrast medium-enhanced magnetic resonance angiography and duplex ultrasound scanning

OBJECTIVE: This study was undertaken to investigate the effects of substituting multi-station total outflow contrast medium-enhanced magnetic resonance angiography (CE-MRA) for color duplex ultrasound (US) scanning on treatment planning in the diagnostic workup of patients with suspected or known peripheral arterial occlusive disease.Patients and methods One hundred consecutive patients referred because of suspected or proved peripheral arterial occlusive disease to a University Hospital underwent both aortoiliac duplex US scanning and multi-station total outflow CE-MRA. For 73 of these patients (57% men; mean age, 62 years) treatment or treatment plans could be retraced. Eighteen patients also underwent femoro-popliteal duplex US scanning. Three experienced vascular surgeons retrospectively formulated two sets of treatment plans based on standardized clinical parameters and either duplex US scanning or CE-MRA. The main outcome measure was proportion of patients for whom the treatment plan matched actual treatment without additional use of intra-arterial digital subtraction angiography. Actual treatment, based on all available information, including results of duplex US scanning, CE-MRA, and any other diagnostic tests, served as the standard of reference. RESULTS: Duplex US scanning provided enough information for treatment planning in 46, 45, and 53 patients versus 67, 68, and 66 patients when CE-MRA was used (surgeons 1, 2, and 3, respectively; surgeons 1 and 2, P <.001; surgeon 3, P =.007). Treatment plans based on duplex US scanning exactly matched actual treatment in 37 of 73 patients (51%; surgeon 1), 36 of 73 patients (49%; surgeon 2), and 46 of 73 patients (63%; surgeon 3). Treatment plans based on CE-MRA exactly matched actual treatment in 56 of 73 patients (77%; surgeon 1), 55 of 73 patients (75%; surgeon 2), and 51 of 73 patients (70%; surgeon 3). Positive predictive value and negative predictive value of duplex US scanning as measures of ability to discriminate between surgical and nonsurgical treatment were 0 of 0 (undefined) and 43 of 46 (93%), 1 of 2 (50%) and 40 of 43 (93%), and 5 of 5 (100%) and 44 of 48 (92%) for surgeons 1, 2, and 3, respectively. For CE-MRA, positive and negative predictive values were 11 of 13 (85%) and 50 of 54 (93%), 10 of 12 (83%) and 51 of 56 (91%), and 8 of 13 (62%) and 48 of 53 (91%), respectively, for surgeons 1, 2, and 3. CONCLUSION: Compared with aorto-iliac and femoro-popliteal duplex US scanning, multi-station total outflow CE-MRA is more effective for treatment planning in most patients with known or suspected peripheral arterial occlusive disease.     

Vascular endothelial cell growth factor and fibroblast growth factor 2 expression in patients with critical limb ischemia

BACKGROUND: For patients with critical limb ischemia (CLI), there is a great need for alternative treatment strategies. One option is therapeutic angiogenesis by administration of vascular growth factors. The lack of convincing clinical data supporting this strategy may be due to the ignorance of endogenous angiogenic processes in CLI. To evaluate the importance of vascular growth factors in the pathogenesis in CLI and provide information for clinical growth factor treatment trials, we determined the levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in the ischemic legs of patients with this disease. METHODS: Skin and muscle biopsies from the calf and groin were gathered from 25 patients with CLI. Control samples came from 10 orthopedic patients and from 5 patients who were undergoing coronary artery bypass. The concentration of VEGF and FGF-2 in the biopsies was measured by enzyme-linked immunoassay, and to localize growth factor production, biopsied sections were immunostained. RESULTS: Patients with CLI had lower levels of VEGF in distal skin samples than in proximal ones (mean difference: 16.7 pg/mg total protein, 95% confidence interval: -1.0 to -32.3, P =.038), but these levels were similar to those in distal samples from control subjects (8.0, -4.6 to 20.5, P =.65). In muscle, VEGF concentrations were similar in calf and groin (5.4, -12.4 to 23.1, P =.55), but distal levels were higher than in distal samples from control subjects (23.7, 1.2 to 56.7, P =.028). Skin FGF levels tended to be higher in distal samples (45.3, 26.5 to 117.5, P =.090) and were higher than in skin from control subjects (106.2, -11.4 to 223.8, P =.050). Also in muscle, distal samples had higher levels of FGF-2 (35.6, -1.6 to 59.7, P =.006), but these levels were similar to what was found in control subjects (29.4., -16.3 to 81.2, P =.39). Growth factors were located in connective tissue between muscle fibers. In skin, the predominant FGF-2 staining was just below the epidermal layer, whereas VEGF appeared in the dermal layer. CONCLUSIONS: The results indicate that there are elevated concentrations of FGF-2 in calf muscle, whereas VEGF concentrations do not appear to be higher in the ischemic part of the leg in patients with CLI. These findings suggest that VEGF supplementation may be a more appropriate strategy for therapeutic angiogenesis to the calf area for CLI than FGF-2.     

Vascular and stromal features in the skin of the lower limb in patients with chronic critical limb ischaemia (CLI) and oedema.

OBJECTIVE: peripheral oedema is often observed in limbs affected by chronic critical limb ischaemia (CLI) and is mainly subcutaneous in distribution. Previous work has shown that capillary filtration coefficient (CFC) in limbs with CLI and oedema was twice as great as that in the contralateral limb. These changes might be due to morphological changes. Transmission electron microscopy (TEM) was used to examine the morphological features of the capillary walls and surrounding stromal tissues in the skin of these limbs. MATERIAL AND METHODS: eight patients with unilateral CLI and peripheral pitting oedema (four men, four women, a mean age of 81+/-6.9 years) was studied. Skin biopsies were taken from the pulp of the first toe, interdigital space between the first and second digits and dorsal part of forefoot just prior to amputation. RESULTS: stromal oedema and dilated capillaries were most prominent in the distal part of the foot. Some of the capillaries were filled with blood cells and some were empty. The endothelium of the dilated vessels was elongated and distended. In some patients a number of capillaries were collapsed with degenerate endothelial cells. , i.e. large openings, were found between the elongated oedematous endothelial cells. The basal lamina was thickened in all patients. Stromal haemorrhage and degeneration were seen in approximately 50% of patients. CONCLUSION: CLI causes ultrastructural changes in the capillary endothelium and surrounding stroma. The presence of large gaps between endothelial cells as well as an increased capillary pressure may enhance transcapillary transudation, and are most likely the causative factors in the formation of the ischaemic oedema. The stromal haemorrhage as well as degeneration probably signifies a terminal stage of CLI.     

Magnetic resonance angiography of peripheral runoff vessels.

Recent improvements in magnetic resonance imaging techniques have made magnetic resonance angiography (MRA) a very useful adjunct to invasive angiography. Fifty-five limbs in 51 patients with occlusive peripheral vascular disease were studied with both MRA and contrast arteriography. The magnetic resonance and contrast arteriograms were read by radiologists and surgeons and separate interventional plans were based on each study. The MRA findings differed significantly from those of conventional arteriography in 26 limbs (48%). In every case MRA visualized all of the same vessels and hemodynamic stenoses seen on the contrast arteriogram. In 48% of the cases, however, MRA revealed additional findings. Thus the discrepancies in the two studies were always the result of the failure of the arteriogram to reveal all of the patent vessels seen on MRA. The additional information provided by MRA resulted in alteration of the interventional plan in 11 cases (22%). In nine cases (18%) target vessels suitable for use in a limb-salvage procedure were identified by MRA, although they had been missed by conventional arteriography. In all of these cases, intraoperative arteriograms confirmed the suitability of these vessels for use in technically successful bypass procedures. In two cases (4%) additional information provided by MRA identified a target runoff vessel for bypass grafting that proved to be a better alternative than the one that would have been chosen on the basis of contrast arteriography.(ABSTRACT TRUNCATED AT 250 WORDS)