Expression and localization of vascular endothelial growth factor in normal abdominal aorta and abdominal aortic aneurysm.

AIM: The genesis of abdominal aortic aneurysms is associated with remodeling of the vascular wall by angiogenesis as well as proteolysis. Vascular endothelial growth factor (VEGF) is known to be a regulator of angiogenesis and to simultaneously stimulate elastolytic proteinases. We analyzed the expression and localization of VEGF in human abdominal aortic aneurysms compared to normal human aorta METHODS: Eighteen infrarenal aortic aneurysm samples were collected at the time of abdominal aortic aneurysm surgery, while nine normal aortic samples were obtained from autopsy specimens. Immunohistochemical staining was performed to detect VEGF. Immunoenzyme or immunofluorescent double staining was also used to identify those cells presenting VEGF. RESULTS: VEGF was expressed in 18 (100%) of the 18 abdominal aortic aneurysm samples, while 0 (0%) in the 9 normal abdominal aorta samples. Of the 18 samples of aneurysms, all 18 displayed positive VEGF immunostaining in macrophages, 12 in smooth muscle cells (SMCs), and 9 in endothelial cells (ECs). CONCLUSION: Our study clearly demonstrated the expression of VEGF in ECs, and SMCs, and macrophages of abdominal aortic aneurysms as well as its absence in those cells of normal abdominal aorta, suggesting that VEGF may play an important role in aneurysm formation via its direct and/or indirect actions.

Three-year cardiovascular events and disease progress in patients with peripheral arterial disease: results from the Japan Medication Therapy for Peripheral Arterial Disease (J-METHOD).

AIM: To investigate the current status of peripheral arterial disease (PAD) drug treatment in Japan, and the effects of drug treatment, risk factors, and complications on disease progress and onset of cardiovascular events in PAD patients. METHODS: In this prospective observational cohort study, 557 PAD patients were followed up for 3 years, and the current status of PAD treatment, risk factors, and cardiovascular events were monitored. RESULTS: Three drugs, i.e., beraprost sodium, cilostazol, and aspirin, were most frequently used. The patients who had undergone vascular reconstruction of the lower limbs before enrollment showed significant improvement in ABI. Among the patients who had not undergone vascular reconstruction before enrollment, there was a significant improvement in ABI after treatment with beraprost. During the observation period, cardiovascular deaths occurred in 35 patients (6.3%), heart diseases in 63 (11.3%), brain diseases in 39 (7.0%), and events in the lower limbs in 94 (16.9%). The factors affecting the increase of the cardiovascular events were explored by multivariate analysis (Cox regression analysis). As a result, age (75 years or older), ischemic heart disease and increase in severity on the Fontaine classification were identified as significant factors for cardiovascular deaths, whereas kidney disorders and increase in severity on the Fontaine classification were identified for heart diseases, the number of oral drugs for treating PAD was identified for brain diseases, and age (younger than 75 years), dialysis, ABI (less than 0.7) and aspirin were identified for the events in the lower limbs. CONCLUSION: As a result of the three-year follow-up on the Japanese PAD cohort, the current status of PAD treatment, risk factors, and cardiovascular events could be identified.

Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques.

AIM: Prostaglandin (PG) receptor agonists are frequently used for the pharmacological treatment of arteriosclerosis obliterans (ASO). In particular, the PG receptors EP2 and IP stimulate vasodilation and inhibit platelet aggregation, biological processes thought to be protective against ASO and important for physiological homeostasis. However it is uncertain whether EP2 and IP exist in diseased arteries, or what their distribution within the artery might be. In this study, we analyzed the distribution of these PG receptors in patients with severe ASO to determine the potential application of stimulation of these receptors as targets for pharmacological treatment. METHODS: We collected segments of atherosclerotic femoral arteries during femoropopliteal bypass surgery and determined the expression levels of EP2 and IP receptors by western blotting. Immunofluorescence was used to observe receptor localization. RESULTS: Findings of western blotting showed an increased Cox-2 expression in patients with ASO. The EP2 as well as IP receptors were each induced approximately 3-fold in comparison to normal samples. The expression of these receptors was increased in the intimal layer as well as the medial layer; their expression was also detectable within the atherosclerotic plaque. CONCLUSION: We observed induction of the PG receptors EP2 and IP in atherosclerotic femoral arteries in the arterial intima, medial layer, as well as the associated atherosclerotic plaque. These results suggest that receptor-selective PG agonists specifically target atherosclerotic arteries and therefore, may find potential application in the pharmacological management of patients with ASO.

Hybrid surgical and endovascular therapy in multifocal peripheral TASC D lesions: up to three-year follow-up.

AIM: The authors described their three-year experience with hybrid surgical and endovascular therapy for multifocal peripheral TASC D lesions, involving both the aortoiliac and/or superficial femoral and common femoral arteries. METHODS: From February 2005 to March 2008, 21 lower limbs in 20 patients with multifocal peripheral artery disease, involving the aortoiliac and/or superficial femoral as well as common femoral arteries, were treated by hybrid surgical and endovascular therapy, such as aortoiliac and/or superficial femoral artery stenting as an adjunct to common femoral artery endarterectomy. Technical and hemodynamic success as well as primary and primary assisted patency and limb salvage rates were determined in concordance with the Society for Vascular Surgery guidelines. RESULTS: All lower limbs successfully underwent successful hybrid surgical and endovascular therapy. The average ABPI before and after hybrid therapy significantly increased from 0.50 +/- 0.32 to 0.79 +/- 0.24 (P = 0.0022). The mean duration of follow-up was 357 days (range, 4 to 1400 days). Over all, the primary patency rates were 94%, 70% and 70% at 6, 12, and 24 months, respectively, and the primary assisted patency rates were 94% at 24 months. The limb salvage rate was 100% at 24 months. The survival rates were 95%, 88%, and 88% at 6, 12, and 24 months, respectively. The primary patency rate for intermittent claudication was significantly higher that that for critical limb ischemia, while no significant difference was found in the assisted primary patency and survival rates between intermittent claudication and critical limb ischemia. CONCLUSION: Hybrid surgical and endovascular therapy, such as aortoiliac and/or superficial femoral artery stenting as an adjunct to common femoral artery endarterectomy, can provide a less invasive yet effective and durable option to patients with multifocal peripheral artery disease.

Fate of varicose veins after great saphenous vein stripping alone.

AIM: The aim of this study was to observe prospectively the clinical sequelae of varicose veins after great saphenous vein (GSV) stripping alone, and to examine whether spontaneous varicose vein regression or disappearance continued for a long period (>3 years). METHODS: Thirty-nine consecutive patients (20 males and 19 females; mean age 57.2), who underwent GSV stripping in Fujita Health University (55 limbs) between November 1, 2002 and December 31, 2003 were enrolled. RESULTS: At four to six weeks, varicose veins spontaneously resolved in 50 limbs (91%), in which subsequent sclerotherapy was not necessary. Five limbs subsequently underwent sclerotherapy for residual varicose veins (5%). At more than three years, 49 limbs (89%) completed the follow-up study. The recurrence after GSV stripping alone occurred in four of the 45 limbs (9%), while those of GSV stripping with sclerotherapy was one of the four limbs (25%). CONCLUSIONS: This study definitely demonstrated that spontaneous varicose vein resolution can continue for more than three years after GSV stripping alone, suggesting that varicectomy can be deferred or avoided in many patients.

Vein patch angioplasty with non-penetrating titanium clips. Comparison to standard suture technique.

Our purpose was to compare the Vascular Closure Staples (VCS) clips to a standard suture technique for vein patch angioplasty in a porcine model. Six female pigs underwent vein patch angioplasty of the common iliac arteries with either VCS clips or continuous suturing. The reconstructed vessels were evaluated macroscopically, angiographically and histologically after two months by re-operation. There was a non significant trend towards shorter reconstruction (6.5 +/- 1.8 min. for clips vs. 8.5 +/- 1.7 min. for sutures, p = 0.15) and clamp times when clips were used (8.4 +/- 1.5 min. vs. 10.1 +/- 1.3 min., p = 0.15). At re-operation all vessels were found patent without significant histological differences regarding the intimal reaction. VCS clips are a reliable alternative to sutures for vein patch angioplasty.

Stent placement in the superficial femoral artery for patients on chronic hemodialysis with peripheral artery disease.

AIM: Chronic hemodialysis is associated with a high prevalence of peripheral artery disease (PAD), and patients on chronic hemodialysis with PAD have an increased risk of critical limb ischemia. The present study assessed the hemodynamic and clinical outcomes of stent placement in the superficial femoral artery (SFA) for patients on chronic hemodialysis. METHODS: Between February 2005 to August 2008, 43 consecutive lower limbs in 42 patients with SFA lesions that were successfully treated by primary stent placement were included in this study. Those were divided into a dialysis group (18 limbs) and a nondialysis group (25 limbs). Outcome measures included primary patency, assisted primary patency, limb salvage, and survival. RESULTS: Patients were significantly younger and presented with significantly more symptomatic limb ischemia in the dialysis group compared to the nondialysis group, despite comparable TransAtlantic Inter-Society Consensus (TASC) classification scores of SFA lesions between the two groups. The primary patency, primary assisted patency, limb salvage, and survival rates of the dialysis group were similar to those of the nondialysis group. CONCLUSIONS: Stent placement in the SFA is a feasible, safe, and effective procedure in patients on chronic hemodialysis with PAD, and may be offered as a first-choice therapeutic option for these patients.

Relationship between parameters of air plethysmography and types of superficial venous reflux in patients with primary varicose veins.

AIM: We investigated whether parameters of air plethysmography (APG) were correlated with types of superficial venous reflux as categorized by ascending venography in patients with primary varicose veins. METHODS: Two hundred and eight limbs with primary varicose veins in 135 patients were evaluated by both APG and ascending venography. Venous hemodynamics was assessed with APG. The location of incompetent vein segments was determined based on the results of ascending venography. RESULTS: Seventy-seven limbs had incompetence of the greater saphenous vein (GSV, G group), 36 had incompetence of the lesser saphenous vein (LSV, L group), and 77 had incompetence of the GSV and LSV (GL group). Twenty-five limbs did not have incompetence of the GSV or LSV (N group). The venous filling index (VFI) differed significantly between the N and the G and GL groups, the L group and the G and GL groups, and the G and GL groups. No significant difference was found between the N and L groups. The venous volume, ejection fraction, and residual volume fraction did not differ significantly among all four groups. CONCLUSION: The VFI as measured by APG discriminates well between limbs with incompetence of the GSV and those without incompetence of the GSV or LSV, and between limbs with incompetence of the GSV and those with the LSV in patients with primary varicose veins, suggesting that the hemodynamic severity of superficial venous reflux progresses with involvement from the LSV to the GSV to both saphenous veins.

Protective effect of sivelestat sodium (Eraspol) on postoperative lung dysfunction in patients with type A acute aortic dissection: a pilot study.

AIM: The authors evaluated the protective effect of sivelestat sodium on postoperative lung dysfunction in patients with type A acute aortic dissection who underwent aortic arch surgery with cardiopulmonary bypass (CPB) under deep hypothermia with circulatory arrest (DHCA). METHODS: Twelve patients with type A acute aortic dissection who underwent aortic arch replacement under CPB with DHCA and were pretreated with or without sivelestat sodium (sivelestat group, N.=7 patients; control group, N.=5 patients) were observed. The ratio of arterial oxygen tension to inspired oxygen fraction (P/F ratio) was measured as a parameter of pulmonary function before and after operation. The number of white blood cells was also counted as an index of inflammatory reaction before and after the operation. RESULTS: The P/F ratio decreased significantly after operation in the control group. However, the P/F ratio was unchanged between before and after operation in the sivelestat group. The number of white blood cells tended to increase after operation in the control group, whereas it decreased significantly after operation in the sivelestat group. CONCLUSION: The present study demonstrated the protective effect of sivelestat sodium on postoperative lung injury in patients with acute type A aortic dissection undergoing aortic arch surgery under CPB with DHCA.

Laser Doppler skin perfusion pressure in the diagnosis of limb ischemia in patients with diabetes mellitus and/or hemodialysis.

AIM: We investigated whether measurement of skin perfusion pressure (SPP), as measured by laser Doppler, can be used to evaluate the severity of limb ischemia in diabetes mellitus (DM) and/or hemodialysis (HD) patients. METHODS: From April 2004 to March 2005, the ankle brachial pressure index (ABPI) and SPP were evaluated in 44 consecutive lower limbs with peripheral artery disease (PAD) and in 24 patients (21 males and 3 females, aged from 45 to 84 years, with a mean age of 69.3 years) with DM and/or HD. Twelve limbs were categorized as Fontaine stage II, 19 as Fontaine stage III and 24 as Fontaine stage IV. RESULTS: The SPP did not differ significantly between limbs at Fontaine stage II and those at Fontaine stage III, but it was significantly lower in limbs at Fontaine stage IV than in those at Fontaine stage II or III. The ABPI did not differ significantly among limbs at Fontaine stages II, III and IV. CONCLUSION: The SPP, as measured by the laser Doppler technique, may be used as a standard for classifying the severity of PAD in patients with DM and/or HD.

Magnetic resonance venography of the lower limb.

Prior to surgery or endovascular therapy for the lower extremity varicose veins or deep venous thrombosis (DVT), ultrasonography provides useful information. But it depends on the operator's technique, each image is limited to a small field of view and interpretation may be subjective. On the other hand, magnetic resonance (MR) imaging is now available with several postprocessing techniques using workstations to demonstrate the gross and objective morphology of these lesions less invasively than the conventional ascending venography. As non-contrast MR venography, fat suppressed three-dimensional (3D) coronal balanced turbo field echo (bTFE) is mainly applied in the semisupine position. The varicose veins on the muscle fascia are easily recognized on volume rendering and the perforating veins can be identified on maximum intensity projection (MIP) and axial multiplanar reconstructions. Gadolinium-enhanced fluid attenuated inversion recovery-bTFE is added when coexisting joint effusion or edema masks the veins. For DVT, direct thrombus imaging (DTI) using fat suppressed 3D coronal inversion recovery-prepared blood suppressed gradient echo sequence is applied. However, the signal intensity of DVT depends on the clot's age on DTI and is sometimes confusing on bTFE. After gadolinium administration, blood shows higher signal intensity than clots regardless of the age and DVT can be easily depicted as filling defects on the axial reformations and summarized on the soap bubble-MIP.

Intermediate-term results of angioscopy-assisted anterior valve sinus plication for primary deep venous insufficiency.

AIM: The intermediate-term efficacy of angioscopy-assisted anterior valve sinus plication for primary deep venous insufficiency was evaluated. METHODS: Twelve limbs in 11 patients had class 4 or higher disease on the SVS/ISCVS classification. Descending venography revealed grade-3 or 4-reflux in all limbs. The limbs were treated with angioscopy-assisted anterior valve sinus plication of the highest valve of the superficial femoral vein. Clinical evaluation and air plethysmography were performed at the final follow-up. RESULTS: The mean follow-up was 38.4 months with a range of 24 to 48 months. Postoperative descending venography revealed significant improvement of the reflux of the superficial femoral vein. At the final follow-up, all patients reported relief of subjective symptoms. The ulcers healed and did not recur in the single limb with class-6 disease, the ulcers did not recur in four class-5 limbs, and there was a distinct clinical improvement with resolution of skin changes in the seven class-4 limbs. The venous filling index measured by air plethysmography was in a normal range in 8 of the 12 limbs. CONCLUSIONS: Angioscopy-assisted anterior valve sinus plication may be a surgical technique that results in intermediate-term clinical and hemodynamic improvement in patients with primary deep venous insufficiency.

Relationship between air-plethysmographic venous function and clinical severity in primary varicose veins.

AIM: The role of air plethysmography (APG) in the diagnosis of chronic venous insufficiency has not been well established. The purpose of this study was to elucidate the relationship between APG parameters and clinical severity in patients with chronic venous insufficiency. METHODS: Two hundred and ninety-four limbs in 154 patients with primary varicose veins were evaluated by APG. Limbs were categorized according to the clinical classification of chronic venous disease suggested by the Ad Hoc Committee on Reporting Standards in Venous Disease of the North American Chapter of the Society for Vascular Surgery and International Society for Cardiovascular Surgery (SVS/ ISCVS). RESULTS: The venous filling index (VFI) was significantly higher in classes 2, 3, 4, and 5+6 than in class 0 or 1, and did not differ among classes 2, 3, 4, 5+6. The ejection fraction did not differ significantly among the 6 classes, and the residual volume fraction was significantly higher in classes 2, 3, 5+6 than in class 0. CONCLUSIONS: APG is a reasonable method for distinguishing the presence or absence of chronic venous insufficiency, but it cannot discriminate the clinical severity. Among APG parameters, the VFI is the most useful diagnostic parameter in the evaluation of chronic venous insufficiency.

Presence of prostacyclin receptor in arteriosclerotic human femoral artery.

AIM: Prostacyclin, which is mainly synthesized by vascular endothelial cells, exerts antiplatelet and smooth-muscle-relaxant effects, thereby maintaining cardiovascular homeostasis. Prostacyclin analogues have been clinically proven to improve ischemic symptoms and prevent the occurrence of vascular events in the lower extremities of patients with arteriosclerosis obliterans. We examined the presence of prostacyclin receptor (IP receptor) in an arteriosclerotic human femoral artery. METHODS: Specimens of the femoral artery were obtained at the time of limb amputation from an 83-year-old woman. Atherosclerotic lesions and associated changes such as calcification were evident. The specimens were stained with hematoxylin and eosin, and processed for immunohistochemistry. RESULTS: A monolayer of cells was observed on the luminal side of the femoral artery. Single immunohistochemistry showed the presence of the IP receptors on cells of the luminal side of the femoral artery. Triple-immunofluorescence staining revealed colocalization of IP-receptor-positive cells and cells positive for von Willebrand factor, a marker of vascular endothelial cells. CONCLUSIONS: We investigated the presence of the IP receptor in the human femoral artery immunohistochemically, and demonstrated their strong expression in endothelial cells. This finding suggests that prostacyclin or prostacyclin analogues may act on their receptors on endothelial cells in patients with arteriosclerosis obliterans.

False aneurysm formation at proximal and distal ends of a stent graft: a rare complication in the repair of endovascular thoracic aortic aneurysm.

This case report demonstrates a rare complication of false aneurysm formation at the proximal and distal ends of a stent graft that was placed in the descending thoracic aorta to repair an atherosclerotic aneurysm with a fibrotic, solid aortic wall. This complication can develop not only in penetrating aortic ulcers and aortic dissections but also in atherosclerotic aneurysms.

Long-term results of treatments for varicose veins due to greater saphenous vein insufficiency.

AIM: The purpose of this study was to determine the long-term recurrence rates of greater saphenous vein (GSV) insufficiency after treatments for primary varicose veins, and to elucidate risk factors for recurrence. METHODS: This was a multicenter retrospective analysis of 376 limbs of 296 patients treated for primary varicose veins due to GSV insufficiency from January 1996 to December 1997. The recurrence-free rates after stripping surgery, saphenofemoral ligation, and sclerotherapy were estimated. The risk factors for the recurrence of primary varicose veins were estimated by multiple regression analysis. RESULTS: The follow-up period was 3.1+/-1.3 (mean+/-SD) years. The recurrence-free rates at 4 years after stripping, saphenofemoral ligation and sclerotherapy were 80.7%, 64.5%, and 51.3%, respectively. The saphenofemoral ligation group and sclerotherapy group had significantly higher recurrence rates than the stripping group (P=0.002, P<0.001, respectively). There was no difference in recurrence rates between the saphenofemoral ligation group and sclerotherapy group (P=0.074). Logistic regression analysis revealed that being female (P<0.029) and treatment without stripping (P<0.001) increased the recurrence rate. CONCLUSIONS: Stripping surgery may be the treatment of first choice for patients with varicose veins due to GSV insufficiency. Patients who have not received stripping surgery and female patients require closer follow-up.

Abdominal aortic aneurysm with left-sided inferior vena cava. Report of a case.

The combination of abdominal aortic aneurysms and congenital anomalies of the inferior vena cava and its tributaries, such as double inferior vena cava, left-sided inferior vena cava, circumaortic renal collar, and retroaortic renal vein, are very rare but of clinical importance to vascular surgeons since these conditions can increase the difficulty of aneurysm resection as well as the risk of venous injury and subsequent excessive bleeding. This report describes a case of an abdominal aortic aneurysm with a left-sided inferior vena cava, and reviews of the incidence, diagnosis, and treatment of these conditions.

Autologous transplantation of peripheral blood endothelial progenitor cells (CD34+) for therapeutic angiogenesis in patients with critical limb ischemia.

AIM: Intramuscular injection of endothelial progenitor cells (EPCs) may constitute an alternative treatment strategy for patients with critical limb ischemia (CLI). We performed transplantations of EPCs (CD34(+)) extracted from peripheral blood in patients with CLI. The objective of this report is to present the method and early results of intramuscular autologous peripheral blood CD34(+) cell transplantation in the ischemic limb. METHODS: CD34(+) cell transplantation was performed in 2 limbs of 2 patients with CLI, in cases in which it was not possible to perform surgical or percutaneous revascularization. The patients received a granulocyte colony-stimulating factor (G-CSF) prior to the treatment. CD34(+) cells were retrieved from peripheral blood and injected directly into the muscle of the ischemic limb. RESULTS: CD34(+) cells retrieved in patient 1 were 1 x 10(5)/ml and in patient 2 were 1.6 x 10(5)/ml. Transcutaneous oxygen pressure in the foot increased and clinical symptoms improved. Newly visible collateral blood vessels were directly documented by angiography. CONCLUSION: Satisfactory clinical improvement was achieved by using peripheral blood EPCs (CD34(+)) in the patients with CLI. No complications arose following the intramuscular administration of peripheral blood CD34(+) cells.

Albumin-coated knitted Dacron aortic prosthses. Study of postoperative inflammatory reactions.

BACKGROUND: The purpose of this study was to investigate the postoperative inflammatory reactions to albumin-coated Dacron grafts (ACGs), which are used in the repair of abdominal aortic aneurysm (AAA). EXPERIMENTAL DESIGN: a retrospective study with a follow-up period of 14 days. SETTING: University hospital. PATIENTS: 50 patients admitted for elective AAA repair from January 1997 to January 2000. INTERVENTIONS: each patient underwent AAA repair with an ACG (Bard, albumin-coated Dacron graft). MEASURES: the white blood cell (WBC) count, plasma C-reactive protein (CRP) concentration, and body temperature (BT) were determined. The preoperative data, the highest values of the postoperative data, and the values 2 weeks postsurgery were analyzed. RESULTS: The BT, CRP, and WBC increased and peaked at the 1st week postsurgery and then decreased gradually. The BT and WBC levels returned to normal within 2 weeks. The CRP level continued to show slightly elevated values in the 2nd week, but it was not significantly different compared to the preoperative data. CONCLUSIONS: The use of an albumin-impregnated prosthesis for the reconstruction of AAA is biocompatible, since no significant increases in inflammatory reactions are observed in the 2nd week postsurgery.