Endothelin-1 levels predict 3-year survival in patients who have amputation for critical leg ischaemia

BACKGROUND: Most patients with critical leg ischaemia (CLI) have co-existing coronary heart disease, which is the main cause of their increased mortality rate. The aim of this study was to investigate whether any markers of endothelial function could predict death in these patients. METHODS: In a cohort of 39 patients with CLI who were scheduled for lower-limb amputation, blood levels of vascular endothelial growth factor, homocysteine, endothelin (ET) 1, von Willebrand factor and vascular cell adhesion molecule 1 were measured, as well as forearm vascular responses to the endothelium-dependent vasodilator acetylcholine. RESULTS: Levels of ET-1 were significantly higher in patients who subsequently died within 3 years than in those who were still alive (P = 0.002) and Cox proportional hazards regression analysis demonstrated that ET-1 was an independent predictor of all-cause mortality:hazard ratio 3.53 (95 per cent confidence interval (c.i.) 1.29 to 9.70; P = 0.007) and cardiovascular mortality:hazard ratio 4.15 (95 per cent c.i. 1.30 to 13.23); P = 0.014. CONCLUSION: ET-1 was an independent predictor of death in these patients with CLI.     

Popliteal-to-distal bypass grafts for critical leg ischaemia

BACKGROUND: To assess the value of revascularization to crural and pedal arteries using the popliteal artery as inflow source. METHODS: Experimental design: Retrospective study with a mean follow-up period of 15.2 months (range, 0-46). Setting: Academic referral center. Patients: 62 patients with critical leg ischaemia and popliteal artery suitable as inflow source for infrapopliteal arterial revascularisation. Interventions: 66 popliteal-to-distal bypass procedures, of which 18 popliteal-crural bypass grafts and 48 popliteal-pedal bypass grafts. Main outcome measures: Bypass graft patency, leg salvage, survival and success defined as patients alive with leg. RESULTS: At 1-month, 1-year, and 2-year follow-up, the primary patency rates were 87%, 58%, and 55%, secondary patency rates were 95%, 70%, and 67%, leg salvage rates were 97%, 88%, and 88%, while 88%, 70%, and 66% of patients were alive with legs at the same intervals. At 2-year follow-up the survival rate was 72%. Above-knee popliteal-to-distal bypasses achieved better primary patency (p=0.02) and corrected primary patency rates (p=0.01) than below-knee popliteal-to-distal bypasses. Diabetes and uraemia affected the survival and patients alive with leg rates. CONCLUSIONS: Popliteal-to-distal bypass surgery is worthwhile for the management of severe, isolated infrapopliteal atherosclerotic disease. Diabetic and uraemic patients are at high risk for both leg and life loss after revascularisation. Grafts originating from the above-knee popliteal artery may achieve better patency rates than those originating from the below-knee popliteal artery.     

'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%.     

Surgical results of leg amputation according to Ghormley's technique in the treatment of chronic lower limb ischaemia

The authors present their experience in the treatment of chronic lower limb ischaemia resulting from atherosclerosis by below knee amputation according to Ghormley's technique, with the immediate application of a semi-rigid plaster cast and early rehabilitation. From a group of 664 patients requiring major amputations, 61 patients (52 men) aged 64 +/- 11 fulfilled the criteria for unilateral below-knee amputation for critical limb ischaemia for atherosclerosis consequences. Peri-operative (30-days) mortality was of 3.28%. Stump healing was very good or good (no need for further surgery) in over 2/3 of patients, but in 20% the need for above-knee amputation developed. Postoperative knee contracture (defined as 15 degrees or more limitation to the movement range) was observed in 11.5% of patients.     

Association of malignant disease with critical leg ischaemia

BACKGROUND: The aim of the study was to determine the prevalence of malignant disease in patients with critical leg ischaemia (CLI). METHODS:: Data for all patients with CLI presenting to a tertiary vascular unit over an 18-month interval were collected prospectively. Patients with clinical, laboratory or radiological features suggestive of malignancy were evaluated further. RESULTS: Of 192 patients admitted with CLI, 22 (11.5 per cent) were found to have an associated malignancy; ten had lung cancer. Fifteen were anaemic on presentation. The prevalence of occult malignancy in patients with acute leg ischaemia was 16 per cent (ten of 62) compared with 9.2 per cent (12 of 130) in those with chronic CLI. Eleven of 22 of patients with CLI and malignancy died within 6 months, compared with 35 (20.6 per cent) of 170 patients with no evidence of malignancy. CONCLUSION: A high prevalence of occult cancer was found in patients presenting with CLI; this was associated with a significantly increased mortality rate at 6 months.     

Redo bypass surgery to the infrapopliteal arteries for critical leg ischaemia.

OBJECTIVES: to evaluate the results of redo bypass surgery to the infrapopliteal artery and the value of adjuvant arteriovenous fistula (AVF) in this setting. DESIGN: retrospective study. MATERIALS: fifty-one redo reconstructions to the infrapopliteal arteries were done for critical leg ischaemia in 45 patients who have had primary infrainguinal reconstructions to the popliteal artery in 20 cases (39%), the crural arteries in 18 (35%), and the pedal arteries in 13 (25%). METHODS: a PTFE prosthesis was used in 21 cases (41%). A Miller cuff was used in 16 prosthetic grafts. Adjuvant AVF was added to three autogenous vein and 12 prosthetic grafts. RESULTS: at 2 years, the primary patency rate was 42%, the secondary patency was 43%, the limb salvage was 67%, the survival was 77%, and 53% of patients were alive with salvaged leg. The primary patency rate with a vein graft was 44% at 1 year, with prosthesis plus AVF 67%, but with prosthesis without AVF only 19%. Secondary patency rates were similar. Prosthetic graft with AVF and those without AVF achieved a 1-year leg salvage rate of 100% and 51%, respectively (p =0.01). Patients with adjuvant AVF had a worse 2-year survival rate that those without AVF (31% vs 89%) (p =0.007; RR: 8.87, CI 95%: 1.62-48.42). CONCLUSIONS: redo bypass surgery using autogenous vein graft may achieve satisfactory long-term results. The use of adjuvant AVF may improve patency of redo infrapopliteal prosthetic bypass grafts.     

Increased angiogenic response but deficient arteriolization and abnormal microvessel ultrastructure in critical leg ischaemia

BACKGROUND: Ischaemia is known to induce angiogenesis, but the effects of critical leg ischaemia (CLI) on angiogenesis remain unclear. The aim of this study was to examine the physiological angiogenic response in CLI by investigating the extent of neovascularization, characterizing microvessel subtypes and determining the microvessel ultrastructure. METHODS: Gastrocnemius muscles were biopsied from 12 patients with CLI and 12 without leg ischaemia. Microvessels were evaluated immunohistochemically using three endothelial markers (anti-CD31, anti-CD34 and PAL-E) and anti-alpha smooth muscle actin (SMA) as a mural cell marker to label arterioles. Ki67 was used to demonstrate active cell proliferation. Further microvessel ultrastructural characteristics were determined by transmission electron microscopy. RESULTS: The CLI group had significantly higher microvessel density and microvessel : muscle fibre ratio for all endothelial subtypes examined (P < 0.001). PAL-E staining demonstrated the highest increase: 4.7 times higher in CLI muscle. There was no significant difference in alphaSMA-positive microvessel density (P = 0.118) or microvessel: muscle fibre ratio (P = 0.214). Ki67 staining showed no active cell proliferation. Transmission electron microscopy showed CLI microvessels had abnormal morphology, mainly a thick basement membrane. CONCLUSION: A physiological angiogenic response was found in CLI, but the microvessels had an abnormal ultrastructure. A lack of active cell proliferation suggests that the angiogenic response may have been exhausted.     

Microdialysate metabolites before, during and after vascular surgery for chronic leg ischaemia.

OBJECTIVE: to investigate peripheral metabolism in the leg during bypass surgery for chronic ischaemia. PATIENTS AND METHODS: in eight patients, microdialysis catheters were placed in the anterior and posterior tibial muscles, subcutaneously in the leg and, for reference, subcutaneously in the pectoral region. Tissue glucose, glycerol and lactate levels were measured between induction of anaesthesia and the first postoperative day. RESULTS:glucose levels increased postoperatively at all four sites. Glycerol levels decreased during the day of surgery. Glycerol was significantly lower in the leg than in the pectoral region. Muscle lactate increased after anaesthesia, but before proximal clamping, and no further significant intra-operative increase was observed. Post-operatively, lactate decreased to baseline levels. Subcutaneous lactate levels followed the changes observed in muscle but did not reach statistical significance. CONCLUSION: bypass surgery for chronic ischaemia temporarily worsens ischaemic metabolism in the leg.     

Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia

BACKGROUND: Spinal cord stimulation (SCS) may have a place in the treatment of patients with inoperable chronic critical leg ischaemia. METHODS: A systematic review and meta-analysis was performed of all controlled studies comparing SCS in addition to any form of conservative treatment for inoperable chronic critical leg ischaemia. Main endpoints were limb salvage, pain relief and clinical situation. Systematic methodological appraisal and data extraction were performed by independent reviewers. RESULTS: Of the 18 reports found, nine trials, comprising 444 patients, matched the selection criteria. After pooling, limb salvage at 12 months appeared significantly greater in the SCS group (risk difference (RD) -0.13 (95 per cent confidence interval (c.i.) -0.04 to -0.22)). Significant pain relief occurred in both treatment groups, but patients who received SCS required significantly less analgesia and reached Fontaine stage 2 more often than those who did not have SCS (RD 0.33 (95 per cent c.i. 0.19 to 0.47)). Complications of SCS were problems of implantation (8.2 per cent), changes in stimulation requiring reintervention (14.8 per cent) and infection (2.9 per cent). CONCLUSION: The addition of SCS to standard conservative treatment improves limb salvage, ischaemic pain and the general clinical situation in patients with inoperable chronic critical leg ischaemia. These benefits should be weighed against the cost and the (minor) complications associated with the technique.     

Serum creatine kinase-B activity in patients with chronic lower-limb ischemia and after leg amputation

Serum creatine kinase-B (CK-B) activity was measured and electrocardiograms (ECG) recorded before and after operation in two groups of ten orthopedic patients. Group I underwent lower-limb amputation because of severe, chronic ischemia of the leg and group II (controls) had knee prosthesis implantation or knee ligament surgery. In group I the number of patients with CK-B activities exceeding the discrimination value (0.25 muka-tal/l) for acute myocardial infarction preoperatively and 2, 24, 48, 72 hours, and at 7 days postoperatively were, respectively, three, three, five, three, two and nil. In Group II the serum CK-B activity remained below the myocardial infarction discrimination value in all patients at all times. No ECG abnormalities indicating myocardial infarction appeared in any patient of either group. The study indicates that severe, chronic lower-limb ischemia and amputation of the leg may cause elevation of non-cardiac CK-B activity in serum that can interfere with enzymatic recognition of acute myocardial infarction.