A systematic review and meta-analysis of early and late outcomes after endovascular angioplasty among patients with thromboangiitis obliterans and chronic limb ischemia.

BACKGROUND: No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients. METHODS: We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis. RESULTS: Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months. CONCLUSIONS: Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable.

The Effect of Smoking Cessation on the Technical Success of Endovascular Treatment for Thromboangiitis Obliterans.

PURPOSE: To show that smoking cessation improves the technical success of lower extremity endovascular treatment in patients with thromboangiitis obliterans (TAO), or Buerger disease. MATERIALS AND METHODS: One hundred two patients with TAO who underwent endovascular treatment for chronic limb-threatening ischemia or severe claudication of lower extremities in a tertiary hospital between 2015 and 2022 were included in this retrospective study. Data on serum cotinine levels were available for the last 45 patients, and 38 patients constituted the study population. Per the institution's protocol, patients were instructed to quit smoking 15 days before the intervention. However, cotinine levels showed that some of the patients continued smoking. Technical and recanalization successes were assessed as the primary end points. The secondary end point was the improvement in Rutherford scores at the 1-month follow-up. The McNemar test was used to compare the proportion of recanalized arteries after the intervention. RESULTS: Thirty-seven men and 1 woman (mean age, 42.9 years ± 10.1) were evaluated. The overall technical success rate was 86.8% in the study group. The technical success rate was significantly higher in the nonsmoker group (n = 24 [96%]) than in the smoker group (n = 8 [61.5%]; P = .006). One-month clinical data were available for 100% of the patients. The Rutherford category of the nonsmoker group was significantly lower at the 1-month follow-up. In addition, the Wilcoxon signed-rank test revealed lower Rutherford scores after the intervention in the nonsmoker group. The adverse event rate was 8%. One (2.7%) patient in the smoker group underwent a minor amputation. CONCLUSIONS: Cessation of smoking before endovascular therapy improved technical success and recanalization rates in patients with TAO.

A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans.

BACKGROUND: Thromboangiitis obliterans (TAO) can lead to the development of critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients (<50 years) still require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has been tested and shown to have reasonable efficacy in CLTI. In this multicenter prospective clinical trial, we evaluated the safety and efficacy of BM-MNC implantation in CLTI patients with TAO.Methods and Results: We enrolled 22 CLTI patients with skin perfusion pressure (SPP) <30 mmHg. The primary endpoint of this trial is the recovery of SPP in the treated limb after a 180-day follow-up period. Secondary endpoints include the pain scale score and transcutaneous oxygen pressure (TcPO2). One patient dropped out during follow-up, leaving 21 patients (mean age 48 years, 90.5% male, Fontaine Class IV) for analysis. BM-MNC implantation caused no serious adverse events and increased SPP by 1.5-fold compared with baseline. Surprisingly, this effect was sustained over the longer term at 180 days. Secondary endpoints also supported the efficacy of this novel therapy in relieving pain and increasing TcPO2. Major amputation-free and overall survival probabilities at 3 years among all enrolled patients were high (95.5% and 89.5%, respectively). CONCLUSIONS: BM-MNC implantation showed safety and significant efficacy in CLTI patients with TAO.

Thromboangiitis Obliterans Biomarker Shifts in Different Acute Phase Stages: A Case Study.

Thromboangiitis obliterans (TAO) is a rare vasculopathy that is predominantly seen in young male smokers. Recently, new biomarkers have been shown to be useful in distinguishing TAO from acute phase TAO in an Asian study population. The present case study illustrates their application in a European patient during TAO exacerbation and their association with therapeutic performance.

Clinical outcomes of extended endovascular recanalization of 16 consecutive Buerger's disease patients.

OBJECTIVE: Buerger's disease is one of the worst diseases causing peripheral artery occlusions (especially lower extremity) with increased morbidity and mortality. Endovascular treatment of the diseased arteries gains preference over bypass surgery nowadays. Here, we aimed to present the clinical outcomes of 16 consecutive Buerger's disease patients underwent extended endovascular recanalization which is a new technique to restore direct blood flow to at least one foot artery, with the performance of angioplasty for each tibial and foot artery obstructions. METHODS: A total of 16 consecutive patients with confirmed diagnosis of Buerger's disease that percutaneously treated in our center between February 2014 and March 2018 were included in the study. The mean age of the patients was 44.25 ± 4.28 ranging from 36 to 50 years. After physical examination and complementary diagnostic tests, performance of extended angioplasty for occluded arteries was intended to restore direct blood flow to at least one of the blow-the-knee arteries. RESULTS: A successful extended endovascular treatment was performed in 20 of 22 limbs, achieving a technical success of 91%. All patients were successfully discharged without any complication. Mean follow-up duration was 21.43 ± 7.08 months. Reintervention was performed in one patient and minor amputation was needed in one of the failed limbs. Limb salvage rate was 100%. A significant difference was observed based on Rutherford classification, ankle brachial index, direct blood flow to foot, presence of ulcer and rest pain when compared before and after the intervention. CONCLUSION: We showed successful extended endovascular recanalization of Buerger's disease patients with a high technical success rate and sustained clinical improvement. Extended endovascular recanalization could be a therapeutic option in Buerger's disease patients, since they are not good candidates for surgery.

[Comprehensive treatment of a patient with Buerger's disease using genetically engineered complexes VEGF-165]. / Kompleksnoe lechenie patsienta s bolezn'iu Biurgera s primeneniem genno-inzhenernykh konstruktsii VEGF-165.

Buerger's disease, also known as thromboangiitis obliterans, is a severe invalidating systemic vascular disease. To one of the modern methods, which is distinguished by its radically new principles of action, as well as holding much promise for further study and application in treatment of patients with lower limb chronic ischaemia induced by thromboangiitis obliterans belongs the use of genetically engineered complexes based on vascular endothelial growth factor VEGF-165 ('Neovasculgen'). 'Neovasculgen' is a genetically engineered complex being a circular DNA (native plasmid on the CELO vector and Ad5), carrying the human VEGF-165 gene, encoding VEGF synthesis. Injection of this drug to the ischaemised tissues of lower extremities ensures long-term synthesis of vascular endothelial growth factor 165 leading to the development of an additional collateral vascular network and consequently to increased perfusion of tissues with oxygen and decreased degree of ischaemia. Presented herein is a clinical case report of a successful therapeutic outcome achieved in a patient suffering for a long time from thromboangiitis obliterans (Buerger's disease) and treated with genetically engineered complexes based on vascular endothelial growth factor ('Neovasculgen') used as a component of comprehensive conservative therapy.

Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease).

BACKGROUND: Thromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease). SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease). DATA COLLECTION AND ANALYSIS: The review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: We only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm2 (standard deviation (SD) 0.70) to 1.48 cm2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm2 (SD 0.62) to 3.59 cm2 (SD 0.14); mean difference (MD) -2.11 cm2, 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.The quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.

How to Treat a Patient with Thromboangiitis Obliterans: A Systematic Review.

To date, there is still no treatment protocol for patients with thromboangiitis obliterans (TAO) who are also afflicted with critical limb ischemia (CLI). Smoking cessation on its own cannot be considered a treatment for the purposes of salvaging a limb of a TAO patient with CLI. The aim of this review was to evaluate different studies of various treatment protocols for avoiding amputation in TAO patients. A systematic search for relevant studies dating from 1990 to the end of 2016 was performed on the PubMed, SCOPUS, and Science Direct databases. Only 24 studies fulfilled the inclusion criteria, of which only one was a randomized controlled trial (RCT). The remaining studies were quasi-experimental with various treatments and follow-up durations. Therefore, meta-analysis was not performed. Judging from the major amputation rates after the suggested treatments were performed, no treatment was particularly effective. This review demonstrated that more standard RCTs are needed to resolve this treatment issue involved in TAO. In addition, because health insurance coverage for TAO patients differs by country, regional cost-benefit and cost-efficacy studies of the suggested treatments for TAO are highly recommended.

Outcomes of endovascular recanalization versus autogenous venous bypass for thromboangiitis obliterans patients with critical limb ischemia due to tibioperoneal arterial occlusion.

OBJECTIVE: This study sought to compare the outcomes of endovascular recanalization (ER) vs autogenous venous bypass (AVB) for tibioperoneal arterial occlusion in thromboangiitis obliterans patients with critical lower limb ischemia. METHODS: A total of 90 limbs in 75 patients, successfully treated with ER (ER group, 35 patients, 43 limbs) and AVB (AVB group, 40 patients, 47 limbs) for tibioperoneal arterial occlusions from January 2009 to December 2015 in a single institution, were retrospectively analyzed. The characteristics and outcomes were compared between the two groups. The primary outcome was the amputation-free survival rate during follow-up; the secondary outcomes were patency rates, immediate failure, periprocedural complications, and rates of reintervention. Univariate and multivariate analysis to identify potentially significant predictors of amputation-free survival and primary patency in the whole study group was performed. RESULTS: Not all patients in the ER group were bypass candidates because of unavailable runoff arteries or adequate conduit for bypass. Other baseline characteristics were similar between groups. Patients in the ER group had a much higher incidence of immediate failure (36.36% in femoropopliteal segment and 65.52% in tibioperoneal segment vs 14.89% in AVB bypass; P = .03 and < .001). Although patients in the ER group had a significantly higher rate of reintervention (62.79% vs 27.66%; P < .001) associated with a significantly lower primary patency rate (18.96% in femoropopliteal segment and 14.37% in tibioperoneal segment vs 60.41% in AVB bypass; P = .008 and < .001) and secondary patency rate (33.85% in femoropopliteal segment and 21.29% in tibioperoneal segment vs 68.78% in AVB bypass; P = .04 and .002) at 3 years, the amputation-free survival in the ER group and AVB group was similar at 1 year (92.9% vs 93.2%; P = .81) and 3 years (87.8% and 90.6%; P = .66). Univariate and multivariate analysis showed that the presence of gangrene was independently associated with major amputation (hazard ratio, 2.24; 95% confidence interval, 1.33-4.3; P = .02); however, the presence of active ulcer was the only risk factor for poorer primary patency during follow-up (hazard ratio, 1.86; 95% confidence interval, 0.55-5.6; P = .04). CONCLUSIONS: ER is a valid strategy for limb salvage in thromboangiitis obliterans patients who are unsuitable for bypass, contributing an acceptable amputation-free survival as high as with AVB, even though it is associated with lower patency rates and a higher rate of reintervention.

Endovascular Therapy Outcomes and Intravascular Ultrasound Findings in Thromboangiitis Obliterans (Buerger's Disease).

PURPOSE: To investigate outcomes of contemporary endovascular therapy and intravascular ultrasound (IVUS) findings in thromboangiitis obliterans (TAO) patients. METHODS: Between April 2007 and January 2016, 20 patients (mean age 45±8 years; 16 men) underwent endovascular therapy for TAO-related lesions in 25 consecutive limbs. Subjects exhibited a broad array of clinical symptoms, including critical limb ischemia (n=15) and claudication (10) in the lower (n=20) and upper (n=5) limbs. RESULTS: Procedure success was achieved in 24 (96%) limbs (complete success in 16 and partial success in 8), all of which exhibited improvements of at least 1 grade of the Rutherford category. Kaplan-Meier analysis showed that reintervention-free rates were 81.9% (95% CI 0.586 to 0.928) at 6 months and 71.7% at 10 months (95% CI 0.473 to 0.862). IVUS was performed in 20 limbs and revealed unique findings, including the "bull's-eye" appearance, "lotus-root" appearance, and "bunch of grapes" appearance. During a mean follow-up of 26±19 months, the limb salvage rate was 100% with no deaths. CONCLUSION: Contemporary endovascular therapy might be able to serve as a potential option for TAO patients with lower and upper limb symptoms. Liberal application of IVUS could help us understand the pathology of TAO to support endovascular therapy for TAO.

[Thromboangiitis obliterans: notions for practice]. / Thromboangéite oblitérante :notions pour la pratique.

Thromboangiitis obliterans is an occlusive vasculopathy affecting small- and medium-size arteries. It can result in severe ischemic status. Thrombophlebitis can be associated. The exact etiology has still to be elucidated. Smoking is the main contributing factor. Diagnosis is based on clinic and paraclinic context, as well as exclusion of other vascular pathologies. Its management consists in complete smoking cessation and instauration of vasodilator treatment. Revascularization is an option that has to be evaluated on a case by case basis. New promising therapeutic approaches are emerging.

La thromboangéite oblitérante se caractérise principalement par une atteinte occlusive des artères de petit et moyen calibres, pouvant mener à un tableau clinique ischémique grave. Une thrombophlébite peut y être associée. L'étiologie exacte n'est pas encore connue. Le tabagisme est le facteur de risque prépondérant. Le diagnostic se base sur les contextes clinique et paraclinique, ainsi que l'exclusion d'autres pathologies vasculaires. La prise en charge consiste en l'arrêt définitif du tabagisme et l'introduction de traitements vasodilatateurs. Les options de revascularisation sont à discuter de cas en cas. De nouvelles modalités thérapeutiques semblent prometteuses.

[Thromboangiitis obliterans (Buerger's disease): state of the art]. / Obliteriruyushchii trombangiit (bolezn' Byurgera): sovremennoe sostoyanie problemy.

Thromboangiitis obliterans (Buerger's disease) is systemic vasculitis with predominant development of thrombotic occlusions of small-to-medium diameter arteries of distal portions of both upper and lower limbs. A distinctive feature of Buerger's disease from other vasculitides is the involvement of the venous bed into the pathological process in the form of migrating thrombophlebitis. The disease is encountered more often in young adult males, predominantly tobacco smokers. The clinical pattern is presented by symptoms of increasing insufficiency of blood supply of tissues of extremities. The diagnosis is made by means of ruling out other vascular diseases (atherosclerosis, diabetes mellitus, systemic diseases of connective tissue, hypercoagulation conditions) based on clinical and laboratory findings, as well as modern methods of visualization, including multislice spiral computed tomographic angiography. Of special importance is a pathomorphological examination aimed at detecting the signs specific for Buerger's disease: arteries showing intimal hyperplasia (from stenosis to complete obliteration according to the capillary angiomatosis type, vascular "recalibration", obliteration of lumens by thrombi, lack of calcification of the tunica media; venous alterations are presented by panphlebitis with intimal hyperplasia, and occlusion with thrombi. Treatment is aimed at eliminating the aetiological stimulus (i. e, smoking), improving blood circulation by means of regular, dosed physical exercises, and administration of anti-ischaemic agents (analogues of prostaglandins, calcium channel antagonists, antiaggregants and anticoagulants). Failure of conservative treatment failed should be followed by making a decision to perform revascularization (endovascular interventions, bypass reconstructive operations, arterialization of the venous blood flow of the foot, resection of the posterior tibial veins, transplantation of the greater omentum onto the crus).

Fate of ischemic limbs in patients with Buerger's disease based on our 30-year experience: does smoking have a definitive impact on the late loss of limbs?

PURPOSE: We herein review the long-term results of our series of critical ischemic limbs caused by Buerger's disease. METHODS: A retrospective review of 103 patients with critical limb ischemia who were diagnosed with Buerger's disease by Shionoya's criteria between 1980 and 2010. RESULTS: The age of onset was 38.0 ± 9.7 years (mean ± SD). The median follow-up was 97 months. Thirty-three patients had pain at rest, and 65 patients presented with ischemic ulcers in their toes and/or fingers. Gangrene was present in five patients. Sixteen patients achieved remission with medical therapy and smoking cessation. Sixty-six patients underwent sympathectomy. Bypass to the crural arteries was performed in 23 limbs, with assisted primary patency rates of 67.0 and 45.6 % at five and 10 years. Graft failure caused major amputation in two out of 10 smokers, but no limbs were lost among the 12 ex-smokers. Therapeutic angiogenesis using cell transplantation led to improvement in three ex-smokers; however, amputation was unavoidable in the one smoker who was treated. The limb salvage rate at 20 years was 90 % in ex-smokers and 69 % in smokers, which was not significantly different. CONCLUSIONS: This study demonstrated no significant difference in the limb salvage rate between ex-smokers and smokers. Our results do not support any advantageous effect of smoking cessation on the long-term remission in patients with Buerger's disease.

Effect of a Low-Intensity Pulsed Ultrasound Device, SX-1001, on Clinical Symptoms in Buerger Disease With Limb Ischemia.

Buerger disease is a rare disease of unknown etiology and cannot be treated by bypass surgery or percutaneous re-endovascularization. Although the need for effective limb ischemia prevention strategies is increasingly being recognized, effective preventative strategies are insufficient. The aim of this study using a new pulsed ultrasound device, SX-1001, is to determine whether treatment using SX-1001 can mitigate rest pain and improve blood supply to ischemic legs in patients with Buerger disease. This study is a multicenter, double-blinded, parallel randomized clinical trial testing the efficacy and safety of SX-1001. Treatment using SX-1001 is expected to result in reduction of the visual analog scale score for pain in Buerger disease patients who have Fontaine stage III. A total of 44 patients from 20 hospitals in Japan will be enrolled. The primary endpoint of the trial is a change in rest pain intensity on the visual analog scale score from baseline to 24 weeks. This trial will be the first to show the safety and efficacy of low-intensity pulsed ultrasound using SX-1001 for clinical symptoms in patients with Buerger disease. Low-intensity pulsed ultrasound may be a new therapy for limb ischemia. Ethical approval has been obtained from each of the participating institutes. Study findings will be disseminated through peer-reviewed journals and at scientific conferences.This study is registered at UMIN Clinical Trial Registry (UMIN000014757).

[THROMBOANGIITIS OBLITERANS (BUERGER'S DISEASE)]. / Maladie de Buerger.

To day there appears to be a consensus to recognize thromboangiftis obliterans (Buerger's disease) as a distinct clinical and pathological entity, characterized by an inflammatory occlusive vasculitis of the small and medium-sized arteries and veins that affects young adult smokers. The strong link with smoking is one of the unique features of thromboangiitis obliterans. Once the disease has became established stepping smoking is the only effective way to prevent evolution of the disease and to reduce the risk of major amputations. Ischaemia of the lower and upper limbs and superficial thrombophlabitis are the essential features of the clinical presentation. However the diagnosis of thromboangiitis is rendered difficult by the lack of specific clinical, radiological, biological and histapathological features. Thus the diagnosis is funded on a probabilistic approach. Discontinuation of tobacco use and to day cannabis are the cornerstone of therapeutic management of patients with thromboangiitis. In patients with ischaemic lesions local care is the other main component of therapeutic management, infusion of iloprost had demonstrated some efficacy.

Endovascular SilverHawk directional atherectomy for thromboangiitis obliterans with occlusion of the popliteal artery.

Thromboangiitis obliterans (TAO), also known as Buerger disease, is a nonatherosclerotic segmental inflammatory disease of small and medium-sized arteries of the distal extremities occurring predominantly in young men who are long-term tobacco smokers. We treated 2 patients who presented with TAO involving popliteal and tibial arteries. Directional atherectomy with a SilverHawk device was used to recanalize the arteries without major complications. During follow-up conducted using computed tomography or sonography, we observed that the treated vessels remained patent. These cases report illustrate the feasibility and immediate effectiveness of endovascular SilverHawk directional atherectomy in TAO patients with occlusion of the popliteal arteries.

Embolus-carried vascular endothelial cell growth factor 165 improves angiogenesis in thromboangiitis obliterans.

We investigated neovasculization effects of embolus-carried human vascular endothelial cell growth factor 165 (VEGF165)-encoded adenovirus (Ad) vector in the hindlimbs of rats with thromboangiitis obliterans (TAO). Rats were equally divided into blank control (I), TAO model (II), embolus (III), Ad-VEGF165 intravascular treatment (IV), Ad-VEGF165 intramuscular treatment (V), and embolus-carried Ad-VEGF165 (VI) groups. After interventional treatment, the neovasculization effect of the test gene was observed using immunohistochemistry. At 1 week after administration, compared with group II, groups V and VI had significantly increased microvessel densities, but no significant difference was observed between groups V and VI. At 2 weeks, groups V and VI exhibited significantly increased microvessel densities. At 1 week after administration, compared with group II, both groups V and VI showed a significant difference in the ratio between the α-smooth muscle actin count and the muscle fiber count, whereas no significant difference was observed between them. At 2 weeks, groups V and VI also exhibited significant differences in these ratios compared with the other groups. We conclude that Ad-VEGF165 promotes neovasculization in ischemic limbs. Embolus-carried Ad- VEGF165 had the most pronounced effect.