Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).
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Acute Disease↗
Biomedical subjects
L Norgren
Publications and source records attributed to L Norgren.
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).
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Acute Disease↗
Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study.
This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200mg bid vs placebo, p = 0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.
Adult↗
Systemic white blood and endothelial cell response after revascularization of critical limb ischemia is only influenced in case of ischemic ulcers.
AIM: The aim of this study was to study the inflammatory response to open revascularization of an ischemic leg in terms of activation of white blood cells (WBC), platelets and endothelial cells. DESIGN: prospective study. METHODS: Venous samples from 21 patients suffering critical limb ischemia (CLI) were drawn before, and 4 weeks after (20 patients) revascularization. Total WBC, differentiated WBC, and platelets were counted. Expression of CD11b/CD18 on granulocytes and monocytes and CD41 on platelets was measured by flow cytometry. Soluble endothelial markers (sICAM-1, sVCAM-1, sE-selectin and sP-selectin) were analysed with ELISA. RESULTS: WBC and granulocyte count decreased in the subgroup of patients with ulcer and gangrene but no change in activation of WBC was recorded. The endothelial marker sICAM-1 decreased while VCAM-1 increased following surgery, most evident in the subgroup with ulcers and gangrene. CONCLUSIONS: This study shows that revascularization of CLI does not significantly influence the inflammatory response in patients with rest pain only, but a limited response of down regulation was found in the ulcer/gangrene patients probably as an effect of healing ulcers.
Aged↗
Experiences of intentional carotid stenting in endovascular repair of aortic arch aneurysms--two case reports.
Endovascular repair of thoracic aneurysms has emerged as an attractive alternative especially in patients at high risk. However, the left common carotid artery limits the use of stent-grafts in aneurysms located in the aortic arch or close to the left subclavian artery. We report two cases with aneurysms in the distal arch and proximal descending aorta, where we have used a carotid stent in juxtaposition to an aortic stent-graft, to gain a longer proximal neck in the aortic arch in an attempt not to rely only on a by-pass graft feeding the left carotid artery.
Aged↗
Normal values and differences between intraperitoneal and subcutaneous microdialysis in patients after non-complicated gastrointestinal surgery.
OBJECTIVE: Visceral ischemia is an early event in the development of shock and organ failure. Microdialysis has been presented as a promising method for detection of visceral hypoxia and ischemia. The aim of this study was to investigate differences in the metabolic response measured by microdialysis between intraperitoneal and subcutaneous locations and to estimate normal values of lactate/pyruvate ratio, glucose and glycerol. MATERIAL AND METHODS: Intraperitoneal and subcutaneous metabolic responses were compared regarding lacate/pyruvate ratio, glucose and glycerol, during 45 postoperative hours in 33 patients undergoing various non-complicated elective major gastrointestinal surgery. RESULTS: Intraperitoneal lactate/pyruvate ratio started around 15 and decreased over time, while subcutaneous levels were stable around 9. Glucose levels were higher intraperitoneally and increased rapidly during the first 9 h to 8.6 mM, while the subcutaneous levels increased during 21 h to 7.5 mM. Intraperitoneal glycerol levels were stable around 100 microM, while subcutaneous values started around 230 microM and then increased. CONCLUSIONS: In a non-complicated postoperative course the lactate/pyruvate ratio and glucose levels are higher intraperitoneally, suggesting a higher postoperative intraperitoneal metabolism. Glycerol levels are higher and increase subcutaneously, suggesting increased postoperative energy demand, particularly in the visceral organs, as being responsible for the lipolysis seen in the subcutaneous tissue.
Adult↗
Arteriogenic gene therapy in patients with unreconstructable critical limb ischemia: a randomized, placebo-controlled clinical trial of adenovirus 5-delivered fibroblast growth factor-4.
The objectives of this study were to assess the safety and potential clinical efficacy of adenovirus-delivered fibroblast growth factor-4 (Ad5FGF-4) by intramuscular injection into patients with critical limb ischemia (CLI). This study was a double-blind, randomized, placebo-controlled study with escalating dose groups of 2.87 x 10(8) to 2.87 x 10(10) viral particles. Thirteen patients with CLI were randomized to receive active drug (n = 10) or placebo (n = 3). Safety evaluations and efficacy parameters (ankle-brachial index, digital subtraction angiograms, magnetic resonance imaging, and scintigraphy) were performed at baseline and for 12 weeks after treatment. Injections of Ad5FGF-4 were generally well tolerated and considered safe. Transfection efficacy at these concentrations may have been limited or local. The small sample size did not allow any firm conclusions regarding clinical efficacy but a trend toward more and slightly larger blood vessels was observed in the angiograms. It is concluded that intramuscular injection of Ad5FGF-4 into CLI patients seemed safe, but transfection efficacy was limited at the assessed doses. Conclusions regarding clinical efficacy are impossible to draw from this small patient cohort.
Adenoviridae↗
Inflammatory markers and IL-6 polymorphism in peripheral arterial disease with and without diabetes mellitus.
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, recognized as an inflammatory disease of the vessel wall, probably accelerated by diabetes mellitus (DM). Elevated interleukin (IL)-6 levels have been associated with increased cardiovascular morbidity and a common polymorphism has been identified in the promoter region of the IL-6 gene. The aim of this prospective study was to investigate inflammatory mediators in PAD patients (+/- DM) and to investigate a possible relationship to the IL-6 gene polymorphism. Five groups of patients (DM, intermittent claudication +/- DM, critical limb ischemia (CLI) +/- DM) and a control group of 20 individuals each were included. Hemoglobin, high sensitive C-reactive protein (hsCRP), creatinine, blood lipids, white blood cells (WBC); CD11b/CD18; vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, sP-selectin; IL-6, IL-8, tumour necrosis factor (TNF)alpha, sTNFalpha-R1 and sTNFalpha-R2 were analysed. The IL-6 gene polymorphism was determined in all groups and also compared with 200 healthy controls from a larger study of blood donors. In a multiple regression analysis, adjusted for gender, smoking and age, the effect of CLI was significantly (p < 0.05) associated with elevated levels of the WBC count, hsCRP, proinflammatory cytokines (IL-6, TNFalpha-R1-2) and endothelial (sICAM, sVCAM) and WBC (CD11b gran) markers. The effect of less advanced PAD (intermittent claudication) was related to an increased concentration of sVCAM-1 and the number of monocytes and granulocytes. DM or leg ulcers were not significantly related to any of the markers. No significant difference in frequency of the various IL-6 genotypes was found between the groups or when compared with the group of 200 blood donors (p> 0.3). Activation of cytokines, endothelial cells and WBC was related to the Fontaine stage of PAD but not to the presence of DM or ulcers. No association was found between the polymorphism in the IL-6 promoter region and PAD.
Aged↗
Intraperitoneal and intraluminal microdialysis in the detection of experimental regional intestinal ischaemia (Br J Surg 2004; 91: 855-861).
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Animals↗
Results of intraperitoneal microdialysis depend on the location of the catheter.
BACKGROUND AND OBJECTIVE: Intraperitoneal microdialysis was recently described as a method for early detection of visceral ischemia. The method seems safe and accurate. The intra-abdominal catheter used may imply variations in results depending on the location of the catheter. The aim of the study was to investigate possible differences in metabolic parameters obtained depending on various locations of the intra-abdominal catheter, compared with using the subcutaneous reference catheter. METHOD: After right-sided hemicolectomy in 12 patients, three catheters were placed and fixed intraperitoneally: one at the anastomosis, one in the omentum and one embedded between the small intestinal loops. A subcutaneous catheter placed in the pectoral region was used as reference. Analyses of lactate/pyruvate ratio and glucose and glycerol levels were done during a period of 45 hours postoperatively. RESULTS: Lactate/pyruvate ratio decreased numerically at all three intraperitoneal locations during the study while the subcutaneous lactate/pyruvate ratio increased slightly. Significant differences between intraperitoneal and subcutaneous locations were found as well as differences between the three intraperitoneal locations. Highest values of the lactate/pyruvate ratio were found at the anastomosis, while the widest range was found at the small intestine. Subcutaneous glucose levels were lower while glycerol levels were higher compared with intraperitoneal values. CONCLUSIONS: In evaluating postoperative metabolism, intraperitoneal microdialysis is influenced by the location of the microdialysis catheter. The same pattern is, however, recorded over time. The juxta-anastomotic region and the small intestinal loop area seem to be the most reasonable locations for measurements.
Aged↗
Postoperative on-line monitoring with intraperitoneal microdialysis is a sensitive clinical method for measuring increased anaerobic metabolism that correlates to the cytokine response.
BACKGROUND: Visceral ischaemia and cytokine release are early stages in the development of shock and multiorgan failure. Because of lack of methods to measure anaerobic metabolism or visceral hypoxia in the early phase, diagnosis is not usually established until shock and organ failure are evident. METHODS: Nineteen patients were studied postoperatively after major abdominal gastrointestinal surgery. A microdialysis catheter was placed intraperitoneally before closure of the abdomen. Analysis of glucose, pyruvate and lactate was performed every second hour and the ratio between lactate and pyruvate was calculated. Peritoneal fluid was collected from a peritoneal drainage for analysis of tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10). RESULTS: Sixteen of the patients had a normal postoperative course; the lactate/pyruvate ratio started at the level of 20 immediately postoperatively and decreased significantly during the first 45 postoperative hours (P = 0.007). A similar pattern was recorded for peritoneal TNF-alpha, which decreased correspondingly (P = 0.003). A correlation coefficient of 0.303 (P < 0.001 ) between lactate/pyruvate ratio and TNF-alpha was found. After an initial short increase, IL-10 decreased over time (P < 0.001). Three of the patients had abnormalities in the microdialysis results, cytokines and clinical outcome. These patients are presented separately. CONCLUSIONS: A normal postoperative course results in a decrease in the intraperitoneal lactate/pyruvate ratio, TNF-alpha and IL-10. A correlation between the intraperitoneal lactate/pyruvate ratio and TNF-alpha was found which suggests that intraperitoneal microdialysis is a sensitive, indirect method in analysing the postoperative intraperitoneal inflammatory response. A complicated postoperative course was preceded by increase of the peritoneal lactate/pyruvate ratio interpreted as splanchnic hypoxia and also an increased TNF-alpha level.
Adult↗
Long-term results after endovascular repair of abdominal aortic aneurysms with the Stentor and Vanguard stent-graft.
PURPOSE: To present a single institution experience of long-term results after endovascular repair of abdominal aortic aneurysms (AAA) with the Stentor and Vanguard stent-grafts. MATERIAL AND METHODS: Twenty-three patients (20 men, 3 women; mean age 68 years, range 53-81 years) were included in this prospective study. A first generation nitinol stent-graft (Stentor) was used in 12 patients and a second generation (Vanguard) in 11 patients. Follow-up was performed with magnetic resonance imaging (MRI) with contrast-enhanced MR angiography (CE MRA) at 1, 6, and 12 months, and thereafter annually (median follow-up 3 years; range 8 months to 8 years). A conventional radiograph of the abdomen was also performed. Before secondary intervention the findings on MRI with CE MRA were confirmed with spiral computed tomography (CT) and/or angiography (DSA). RESULTS: Only one patient (4%) had no complication. Endoleak was found in 15 patients (65%), graft migration in 8 (35%), and graft deformation in 18 (78%). Secondary endovascular repair was required in 7 patients (30%) and 7 (30%) were converted to open repair. CONCLUSION: Complications with the Stentor and Vanguard stent-grafts were common. Long-term follow-up of endovascularly repaired AAA is mandatory.
Aged↗
White blood cell and endothelial cell response to endovascular procedures in the leg.
AIM: The longterm patency of endovascular procedures is partly depending on restenosis by intimal hyperplasia, a process depending on inflammatory mechanisms resembling the mechanisms of normal repair and the process of atherosclerosis. The aim of this study was to characterize the inflammatory response of white blood cells (WBC) and endothelial cells following endovascular procedures in the leg. METHODS: Venous blood samples were drawn from a cubital vein before and 2 hours after intervention in 19 patients suffering from peripheral arterial occlusive disease (PAOD). Flow cytometry was used to identify and determine the concentrations of WBC and platelets and to measure CD11b/CD18 on WBC and CD41 on platelets. Soluble endothelial markers (sICAM-1, sE-selectin, sP-selectin and sVCAM-1) were measured by ELISA technique. RESULTS: WBC were downregulated following endovascular procedures. The endothelial cell response was limited and only downregulation of sP-selectin reached significant levels. The results were more evident in the group of patients with critical limb ischemia (CLI) compared to patients with intermittent claudication (IC). CONCLUSION: Endovascular procedures in the leg evoke only a limited response which is depending on the degree of ischemia and the magnitude of the interventional procedure.
Aged↗
Effect of Iloprost infusion on metabolism in critical limb ischemia, utilizing microdialysis. A pilot study.
AIM: In critical limb ischemia (CLI), the prognosis to keep the leg is poor if revascularisation is not possible. Treatment with prostanoids has proven to be beneficial regarding pain relief, ulcer healing and limb salvage but only in a proportion of patients. Prostanoids exert their effect in different ways e.g. on white blood cells and endothelial cells. No study has so far investigated the effect of prostanoids on the local tissue metabolism. The aim of this study was to investigate if infusion of the prostacyclin analogue, iloprost (PGI2) improves the local metabolism measured by microdialysis technique. METHODS: Eleven patients, 7 men and 4 women, median age 75 years (range 64-89 years), suffering CLI (Fontaine stage III and IV), were included. Patients with insulin dependent diabetes mellitus were excluded. Microdialysis catheters (CMA 60) were inserted subcutaneously in the ischemic leg and in the pectoral region, respectively. An iloprost infusion was given for 6 hours during 3 days preceded by a control day. Registrations of glucose and lactate levels were performed hourly. RESULTS: No significant differences were found in lactate or glucose levels over the treatment period but a trend of increasing glucose and decreasing lactate was observed. Compared to the control day, lactate was significantly lower during (p=0.02) and after (p<0.05) the infusion. This was also true for the reference catheter during the infusion period (p=0.02). CONCLUSIONS: No immediate improvement in glucose or lactate levels in ischemic tissue could be observed after 3 days of iloprost infusion, but a significant lactate decrease was found compared to a previous control day, suggesting a possible metabolic response.
Aged↗
Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients.
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Adult↗
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.
Aged↗
Human intraperitoneal microdialysis: increased lactate/pyruvate ratio suggests early visceral ischaemia. A pilot study.
BACKGROUND: Previous studies suggest that visceral ischaemia precedes shock and multiple organ failure, though methods for studying humans are lacking. We aimed to evaluate intraperitoneal microdialysis, a new technique for detecting splanchnic ischaemia in clinical practice. METHODS: Right-sided hemicolectomy was performed in eight patients who were studied by microdialysis postoperatively for glucose, lactate, pyruvate and glycerol levels. RESULTS: Six of the eight patients showed a normal postoperative course and had lactate/pyruvate ratios between 7.1 and 21.7, glucose between 4.5 and 14.3 mmol/L and glycerol between 10.4 and 296 micromol/L. In one patient, intraperitoneal lactate/pyruvate ratio and glycerol increased and glucose decreased 5 h before low oxygenation appeared. Another patient exhibited a period of increased lactate/pyruvate ratio before a period of atrial fibrillation. CONCLUSION: Intraperitoneal microdialysis was performed safely. Two out of the eight patients exhibited changes of metabolic markers followed by clinical symptoms that were probably related to transient visceral ischaemia. Our findings suggest that intraperitoneal microdialysis may become a useful tool for monitoring splanchnic ischaemia in clinical practice.
Aged↗
Measurements before endovascular repair of abdominal aortic aneurysms. MR imaging with MRA vs. angiography and CT.
PURPOSE: 1) To compare measurements obtained with MR imaging (MRI)/contrast-enhanced MR angiography (CE MRA) with measurements obtained with angiography (DSA) and CT, for stent-graft sizing of abdominal aortic aneurysms (AAA). 2) To compare MRA measurements obtained with the two post processing techniques MIP (maximum intensity projection) and VRT (3D volume rendering technique). MATERIAL AND METHODS: The prospective study included 20 consecutive patients with AAA identified by DSA and CT as suitable for endovascular repair. For the study, MRI/CE MRA was performed. Five measurement variables for stent-graft sizing were chosen. Comparisons were made between MRI/CE MRA, DSA and CT, and between observers. Comparisons were also made between MIP and VRT. RESULTS: Significantly shorter lengths were obtained with MRA-MIP than with DSA. Three out of six diameter measurements were significantly smaller on MRI/CE MRA than on DSA and CT. No significant differences were found between the observers. One diameter measurement was significantly smaller on MIP than on VRT, while the other measurements showed no significant differences. CONCLUSION: The length measurements obtained with MRA-MIP were probably more correct than those with DSA. For more reliable diameter measurements with CE MRA, improvements of the technique, including VRT reconstructions and a standardized determination of the vessel boundaries, are needed.
Aged↗