Cardiac Regeneration with Human Pluripotent Stem Cell-Derived Cardiomyocytes

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

Cardiac Regeneration with Human Pluripotent Stem Cell-Derived Cardiomyocytes

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.

Cell Therapy for Diabetic Neuropathy Using Adult Stem or Progenitor Cells

Diabetic neuropathy (DN) is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM)-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

Cardiovascular repair with bone marrow-derived cells

While bone marrow (BM)-derived cells have been comprehensively studied for their propitious pre-clinical results, clinical trials have shown controversial outcomes. Unlike previously acknowledged, more recent studies have now confirmed that humoral and paracrine effects are the key mechanisms for tissue regeneration and functional recovery, instead of transdifferentiation of BM-derived cells into cardiovascular tissues. The progression of the understanding of BM-derived cells has further led to exploring efficient methods to isolate and obtain, without mobilization, sufficient number of cell populations that would eventually have a higher therapeutic potential. As such, hematopoietic CD31+ cells, prevalent in both bone marrow and peripheral blood, have been discovered, in recent studies, to have angiogenic and vasculogenic activities and to show strong potential for therapeutic neovascularization in ischemic tissues. This article will discuss recent advancement on BM-derived cell therapy and the implication of newly discovered CD31+ cells.

A Case of Complete Resolution of Aortic Dissection in the Descending Thoracic Aorta Treated with Endovascular Stent-Graft Implantation

The aortic dissection is an acute aortic syndrome, caused by an intimal tear and subsequent splitting of the media by the pulsatile blood flow. Though there would be differences in the origin of aortic dissection and therapeutic modalities, the intermediate and long-term prognoses are poor. Endovascular Stent-graft implantation is a revolutionary technique in the treatment of aortic dissection. The endovascular stent grafting in aortic dissection is less invasive and feasible method and is an effective tool for closing the entry site and promoting clot formation, reducing the size of the false lumen. Therefore, endovascular Stent-graft implantation makes possible the desirable remodelling of aorta. We report 33 year-old male with aortic dissection in the thoracic aorta, which was treated with endovascular Stent-graft implantation. Over the favorable remodelling, his dissection was healed completely by the endovascular treatment using Stent-graft.

Carotid Artery Stenting in Patients With Takayasu's Arteritis:Early and long-term follow-up results

Takayasu's arteritis is a chronic inflammatory disease of unknown etiology involving the aorta, major branches of aorta, and pulmonary arteries and leads either stenosis and occlusion of the involved artery or aneurysm formation or both. The clinical course and prognosis are variable according to two major prognostic factors, ie, complications and the pattern of the past clinical course, as well as by ESR. Though the aggressive medical and surgical treatment are required for patients with a major complication and a progressive course, surgical reconstruction entails a high incidence of suture line complications including stenosis or dilatation. Moreover all the vascular lesions are amenable for vascular surgery. Initial reports revealed excellent results of percutaneous transluminal angioplasty (PTA) in patients with Takayasu's arteritis. However the suboptimal results and restenosis have been the main limitations of the PTA. Stenting has some benefits for early elastic recoil of the fibrotic vessels and restenosis as in other large vessels in Takayasu's arteritis or atherosclerosis. We report early and long-term results of two cases of carotid stenting in patients with symptomatic carotid stenosis and Takayasu's arteritis, which revealed variable angiographic results according to clinical courses and recommend that stenting in Takayasu's arteritis may be another treatment modality in inactive Takayasu's arteritis.

Percutaneous interventional therapy for whole body arterial occlusive disease / 대한내과학회지

BACKGROUND: The goal of percutaneous transluminal angioplasty(PTA) is recanalization of the arterial stenosis or occlusion. The low incidence of serious complications makes PTA an attractive form of treatment for selected patients, especially if the lesions are not severe enough to warrant surgery or the patient is at high operative risk. The purpose of this study was to assess the feasibility, safety, and efficacy of PTA as an alternative or primary therapy for whole body arterial occlusive disease. METHODS: PTA was performed in 397 patients(male 342, female 55 : mean age 58.9+/-12.4 yr) with arterial occlusive disease. The patients were followed after PTA for a mean period of 22+/-11months. The information on restenosis, recurrence of symptom, redo-PTA, bypass surgery and amputation was obtained by follow-up angiography, plethysmography and self-administered questionnaire. RESULTS: In the 313 patients who underwent PTA for low extremity vascular disease, the overall success rate was 80.6%. Technical success rate for the iliac lesions was 84.7%, for the femoropopliteal lesions 74.8%, and for the infrapopliteal lesions 78.6% respectively. These results showed that outcome for iliac lesions were significantly better than those for femoropopliteal lesions(p<0.001). The technical success rate for the low extremity vessels was greater in the stenting group than in the ballooning group(98.2% vs 68.9%, p<0.001). In 260 lesions followed after PTA for low extremity vascular disease, cumulative patency rate at 3 years was greater in the iliac artery group than in the femoropopliteal artery group (84.6% vs 50.8%, p<0.001). In femoropopliteal lesions, cumulative patency rate at 3 year was greater for intervention of stenotic lesions compared to occlusive lesions(60.3% vs 38.1%, p<0.05). Carotid artery stenting in 25 patients(35 lesions) was successful in all lesions. Angiography and/or duplex sonography which was performed at 5.5+/-2.6 months in 18 patients(24 lesions) followed after carotid stenting revealed no evidence of restenosis. Subclavian artery stenting in the 16 patients(17 lesions) was successful in 16 lesions(94%). Renal artery stenting in the 17 patients(18 lesions) was successful in all lesions. Angiography at 8.5+/-3.5 months in 6 patients(6 lesions) followed after renal stenting revealed no evidence of restenosis. PTA for total occlusion of abdominal aorta was successful in 11 lesions(84.6%) of the 13 lesions. Angiography at 13+/-12 months in 7 patients(7 lesions) followed after PTA for abdominal aorta revealed significant restenosis in 2 patients. Minor complications during the PTA for peripheral disease occurred in 25 patients of 397 patients. CONCLUSION: PTA for whole body arterial occlusive disease can be performed with an excellent technical success rate and minimal morbidity and mortality. PTA for carotid, subclavian, renal, iliac artery or abdominal aorta represents a true alternative to vascular surgery as a first-line treatment. Despite acceptable initial success rate, PTA for femoropopliteal or infrapopliteal artery warrants further validation because it has high incidence of clinical restenosis during the follow-up periods.

Polyarteritis Nodosa Presenting as Acute Myocardial Infarction

Coronary involvement of polyarteritis nodosa (PAN) is rarely identified at premortem. Herein, we report a case of PAN presenting as acute myocardial infarction (MI). A 66-year-old man without previous history of heart disease presented with excruciating substernal chest pain of 3 hours duration. On admission, cardiac enzyme and ECG changes were compatible with acute MI of inferior wall. Emergency coronary angiography showed multiple aneurysmal dilatations of both left and right coronary arteries (RCA) and total occlusion with large thrombi at mid-RCA. After balloon angioplasty and intracoronary urokinase, huge coronary aneurysm was defined at mid-RCA and coronary flow partially improved. The patient was transferred to coronary care unit and continous intravenous heparin infusion was started. On the 7th hospitalization day, the patient was discharged in good condition. Two months later, follow-up coronary angiography showed no significant luminal narrowings in RCA with multiple aneurysmal dilatation, but abdominal angiography revealed multiple aneurysms in right renal and superior mesenteric arteries. These findings were compatible with the diagnosis of PAN. The patient was started on prednisone 60mg once daily and cytoxan 125mg bid. At follow-up 8 month later, there was no recurrence of symptoms.

Carotid artery stenting in patients with symptomatic coronary artery disease

Carotid artery stenting has been accepted as a potential alternative to carotid endarterectomy in patients with significant carotid artery stenosis. The objective of this study was to evaluate the feasibility, safety and long-term outcome of percutaneous stenting of carotid artery stenosis in patients with coexisting symptomatic coronary disease. Between May 1996 and May 1999, we performed carotid artery stenting at 48 lesions in 36 patients with carotid stenosis of 60% and symptomatic coronary artery stenosis. Twenty-one patients (58%) had neurologic symptoms. Carotid stenting was performed in 43 internal, 2 external and 3 common carotid lesions. We used Wallstent in 46 lesions, Palmaz stent in 2 lesions and Microstent II in 1 lesion. Staged or combined coronary intervention was performed in 18 patients (50%) and staged coronary artery bypass surgery was performed in 6 patients (17%). In the other 12 patients (33%), medical treatments were performed. Carotid stenting was successful in all lesions. Simultaneous bilateral carotid stenting was performed in 11 patients (31%). One major and 1 minor stroke developed during the procedure. There were no deaths during the procedures and within 30 days post-procedure. During the follow-up of 14 +/- 7 (3 to 40) months, there were no deaths or neurological events. On follow-up (6 +/- 1 months) angiography and/or duplex sonography of 44 eligible lesions in 32 patients, there were 2 cases of asymptomatic restenosis (4.5%) which developed in Palmaz stents implanted at the external carotid artery and the common carotid artery, respectively. In conclusion, carotid artery stenting in patients with coexistent carotid and coronary artery disease is feasible, safe and shows favorable follow-up outcomes.

A Randomized Comparison of Cilostazol and Ticlopidine after Coronary-artery

BACKGROUND AND OBJECTIVES: Combination of ticlopidine and aspirin has been accepted as a standard antiplatelet regimen after coronary stenting because it reduced the rate of cardiac events and hemorrhagic-vascular compli-cations compared with intensive anticoagulation. Ticlopidine use, however, may accompany serious side effects such as neutropenia or liver dysfunction. Cilostazol, a c-AMP phosphodiesterase inhibitor, is a novel antiplatelet agent which is known to have less side effects. MATERIALS AND METHODS: We compared the efficacy and safety of ci lostazol plus aspirin (CA) with ticlopidine plus asprin (TA) after elective coronary stenting. Patients were randomly assigned to receive either CA or TA two days before stenting. The primary end point was a composite of angiographic stent thrombosis, death, myocardial infarction (Q or Non-Q), repeat intervention or bypass su rgery at 30 days. The secondary end points were hemorrhagic-vascular complications, or drug side effects such as neutropenia, thrombocytopenia, or any side effects requiring cessation of drugs at 30 days. RESULTS: After randomization of 300 patients equally to each group, 4 patients were excluded from the analysis: 1 failure of stenting, 3 follow-up loss. The primary end point was reached in 2 patients (1.4% ) in CA group and 3 patients (2.0% ) in TA group (p=1.0). The rate of hemorrhagic-vascular complications was not different between the gr oups (1.4% vs 2.0%, p=1.0). The incidence of significant drug-related side effects was not statistically different between CA group and TA group (0.7% vs 2.7%, p=0.37). However, serious side effect such as neutropenia was seen only in TA group. CONCLUSION: Compared with TA, CA has comparable effect for the prevention of stent thrombosis and major cardiac events with similar rate of hemorrhagic-complications and drug-related side effects after elective coronary-artery stenting. Thus CA regimen can be a safe alternative to TA in elective implantation of coronary artery stent.

A Case of Giant Aneurysm of Coronary Arteriovenous Fistula Treated by Percutaneous Deployment of Embolization Coil

Communication between coronary arteries and cardiac chambers or large vessels is unusual type of congenital malformation. Aneurysmal formation of a coronary arteriovenous fistula is even rare. We report a case of 83-year-old women with giant aneurysm of the coronary arteriovenous fistula from the left anterior descending coronary artery treated by percutaneous deployment of embolization coil.

Early Results of Subclavian Artery Stenting

BACKGROUND AND OBJECTIVES: Though the surgical intervention of subclavian artery stenosis has been effective, its high morbidity and mortality have limited its clinical application. In 1980 percutaneous balloon angioplasty of stenotic artery was introduced as a substitute for surgical intervention and subsequent reports have supported its efficacy noting that it is more effective when combined with stent. The purpose of this study was to assess the feasibility, safety, and efficacy of percutaneous intervention as an alternative or primary therapy for symptomatic subclavian artery stenosis. METHODS: Between September 1993 and October 1998, 17 lesions in 16 patients of symptomatic subclavian artery stenosis were enrolled as candidates for nonsurgical intervention. We performed percutaneous balloon angioplasty with stenting to the subclavian artery stenosis and evaluated the early results. RESULTS: 1)The patients had a mean age of 55+/-14 years and 13 of 16 patients were male. 2)Subclavian artery stenting was successful in 94% (16/17) of the lesion without significant complications. The cause of failure was suboptimal result after deployment of stent. 3)The types of stents deployed were Strecker stents in 4, Palmaz stents in 8, Wall stents in 3 and Jo stents in 2 cases. 4)The peak and mean pressure gradient reduced from 58.5+/-17.0 to 8.5+/-7.4 and 31.4+/-13.0 to 4.7+/-5.5 mmHg respectively (p<0.01) and the degree of luminal stenosis decreased from 92.5+/-8.5% to 10.0+/-14.3%. (p<0.01) CONCLUSION: Subclavian artery stenosis can be managed safely and effectively through percutaneous balloon angioplasty with stenting, with an excellent technical success rate and less morbidity and mortality particularly in patients coexisting other vascular and systemic diseases. However, the long-term patency and clinical effects should be warranted.

Genetic Polymorphism of PAI-1 Gene and Cardiovascular Disease: eta-analysis of Case-Control Studies

BACKGROUND: Previous reports have suggested that alleles at the plasminogen activator inhibitor-1 (PAI-1) gene are associated with increased risk of developing coronary artery disease, including myocardial infarction and stroke through their effect on PAI-1 levels. Method: We attempted to search English literatures for all reports of possible effects of PAI-1 gene on cardiovascular disease in human published prior to November 1998. We used a Mantel-Haenszel method (fixed effect model) and random effect model, respectively, to perform a meta-analysis of 7 case-control studies that provided information related to the effects of PAI-1 gene on risk of cardiovascular disease. RESULTS: From 7 studies for diagnosed cardiovascular disease, the relative frequencies of the three genotypes among controls was (5G/5G) (homozygous normal), 24.5%; (4G/5G) (heterozygous), 48.2%, and (4G/4G) (homozygous for the mutant, 675 GGGG), 27.3%. These relative frequencies in cases were 21.7% for 5G/5G, 48.0% for 4G/5G, and 30.3% for 4G/4G. In fixed effect model, compared with those with genotype (5G/5G), the overall odds ratio (OR) for cardiovascular disease among those with (4G/5G) was 1.12 (95% CI, 0.93 to 1.34), and it was 1.20 (1.01 to 1.44) for the (4G/4G) genotype. For five studies with myocardial infarction as the outcome, the overall OR of myocardial infarction was 1.20 (0.99 to 1.47) for those with (4G/5G) and 1.24 (1.00, 1.54) for those with (4G/4G) genotypes, respectively. CONCLUSION: Our findings provide support for the weak association between PAI-1 gene and cardiovascular disease, in particular, myocardial infarction.

A Case of Transluminal Stent-Graft Implantation at Right Subclavian Artery Pseudoaneurysm in Behcet's Syndrome

Behcet's disease is an uncommon disorder characterized by clinical triad of relapsing iritis, ulcer of mouth and genitalia. It is now recognized as a systemic disorder with mucocutaneous, ophthalmic, intestinal, respiratory, musculoskeletal, cardiovascular, urogenital and neurologic involvement. Systemic complications affecting the arterial system of disease are rare and mainly the aorta and iliac arteries are involved. Invasion of arterial wall is the most common lesion, predisposing to false aneurysm or rupture. As the standard open surgery, although often difficult, needed second surgeries in 30% to 50% of the patients due to the occurrence of anastomotic false aneurysms, endovascular repair emerged as an alter-native treatment of aneurysmal or pseudoaneurysmal manifestrations in Behcet's disease. We report here a case of the pseudoaneurysm at right subclavian artery which is successfully treated with percutaneous stent-graft.

A Study of Major Gene Dominant Family for Factor VII Concentration: Segregation Analysis / 한국역학회지

Elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII levels. We used maximum likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether Mendelian inheritance of a major gene could best explain the familial distribution of factor VII. The study population included 414 family members of 67 subjects who had undergone elective coronary arteriography. The factor VII level was adjusted for age, gender, body mass index, smoking and alcohol drinking (R2=20.6%). Factor VII levels revealed strong familial aggregation with estimated correlation spouse of 0.12, parent-offspring of 0.31, and siblings of 0.40. Regressive models were used to examine inter-individual variation in adjusted factor VII levels in these 67 families. This analysis strongly favored a major gene model with codominant transmission. Genotypic means were 111.6, 123.2, and 184.3% with relative frequencies of 59.4%, 35.4%, and 5.2%. This putative major gene explains 39.9% of the total variance of factor VII. Likelihood was used to search for etiologic heterogeneity by sorting pedigrees into groups that favor one model over another. Compared to pedigrees less favoring Mendelian models, pedigrees favoring Mendelian codominant models have almost 8 times earlier onset of coronary heart disease. These family data suggest that there are strong familial and genetic effects on the factor VII activity in these high risk families. Therefore, linkage studies in these families may be worthwhile to clarify the molecular basis of factor VII levels.

Frequency of Combined Atherosclerotic Disease of the Coronary, Periphery, and Carotid Arteries Found by Angiography

BACKGROUND: The real incidence of atherosclerotic lesions in carotid and peripheral arteries in coronary artery disease patients is not well known in Korea. The aim of this study was to prospectively evaluate the prevalence of atherosclerotic involvement of the coronary, carotid, and peripheral arteries in each arterial disease patients. This study was also designed to evaluate the risk factors, the clinical characteristics of associated carotid artery stenosis in patients with coronary artery disease, and associated peripheral vascular disease in patients with coronary artery disease. METHODS: Between June 1996 and March 1998, 475 patients (369 males, 106 females, mean age 60+/-10 years) were studied. Three hundred and seventy-three patients who presented with ischemic symptoms were enrolled in the coronary artery disease group, 81 patients were enrolled in the peripheral vascular disease group due to presenting claudications, and 21 patients were enrolled in the carotid stenosis group due to presenting cerebrovascular symptoms. Coronary angiography was done by the routine method. Carotid angiography was performed at the aortic arch by the digital subtraction angiography method. Peripheral vascular angiography was taken from the suprarenal abdominal aorta to both femoral arteries. RESULTS: 1) Risk factors for coronary stenosis, peripheral vascular disease, and carotid stenosis: The risk factors were not different between coronary stenosis, peripheral vascular disease, and carotid stenosis groups, but smoking was more frequent among patients with peripheral vascular disease than in patients with coronary stenosis (p-value=0.001). 2) Coronary artery stenosis and carotid artery stenosis: The mean age of coronary artery patients with carotid stenosis was significantly older (p-value=0.006) than for patients without carotid stenosis. The prevalence of peripheral vascular disease was more common in patients with carotid stenosis than in patients without carotid stenosis. 3) Coronary artery stenosis and peripheral vascular disease: Carotid stenosis was more common inpatients with peripheral vascular disease than in patients without peripheral vascular disease in the coronary stenosis group. 4) Prevalence of coronary, carotid, and peripheral artery disease: In patients with coronary stenosis, the prevalence of carotid stenosis was 13.9% and that of peripheral vascular disease was 29.2%. In patients with peripheral artery stenosis, the prevalence of coronary stenosis was 45.7% and that of carotid artery disease was 33.3%. In patients with carotid stenosis, the prevalence of coronary stenosis was 81.0% and that of peripheral vascular disease was 52.4%. CONCLUSION: Carotid artery disease and peripheral vascular disease developed concurrently with coronary artery disease in a significant proportion of patients. Therefore, routine angiography of peripheral and carotid arteries in patients with coronary artery disease is considered, especially in old age.

Simultaneous Bilateral Carotid Stenting in de Novo Internal Carotid Artery Stenosis in Patients at High Surgical Risk

BACKGROUND AND OBJECTIVES: For patients with bilateral carotid artery stenosis, simultaneous bilateral carotid endarterectomy is rarely performed due to a higher perioperative risk for death and strokes. We assessed the immediate and long-term outcomes of simultaneous bilateral carotid stenting (SBCS) for internal carotid stenosis in patients at high surgical risk. MATERIALS AND METHODS: We analyzed 10 patients who underwent SBCS for de novo stenoses of both internal carotid arteries (ICA). Included were those who had 60% to 99% stenosis of extracranial ICAs irrespective of neurologic symptoms and had more than 2 risk factors of Mayo grade III (medical risks) or IV (neurologic risks). RESULTS: The patients had a mean age of 67+/-7 years. Technical success was achieved in all lesions. The mean percent diameter stenosis was reduced from 79+/-13% to 8+/-8%. A total of 21 Wallstents were deployed at 20 lesions. One patient had a minor stroke just after the procedure which was completely resolved with local injection of urokinase. There were no deaths, major strokes or myocardial infarctions during the 30 day follow-up. Six months imaging studies were available on all 9 eligible patients with 18 lesions by duplex sonography and angiography. Late clinical follow-up at a mean of 15.1+/-8.1 months revealed no occurrence of neurologic event or death. CONCLUSION: SBCS is feasible, safe and effective to treat bilateral de novo ICA stenoses in patients at high surgical risk. The procedure, however, is investigational and more experience is required to define its role in the treatment of this patient population.

Bifurcated Stent-Graft(Vanguard) for the Endovascular Treatment of Abdominal Aortic Aneurysm

PURPOSE: The purpose of this study was to evaluate the safety, feasibility and effectiveness of an endoluminally-placed bifurcated stent-graft (Vanguard) for the treatment of infrarenal abdominal aortic aneurysm (AAA). METHODS: Transluminal endovascular stent-graft placements were attempted in 29 patients (28 male, mean age 69+/-7 years) with AAAs involving the common iliac arteries from Aug. 1997 to Jan. 1999. Endovascular therapy was performed in the cardiac catheterization laboratory with epidural anesthesia. One side of the femoral artery was opened by surgical cutdown for the bifurcated stent-graft entry and the other side was punctured percutaneously for the straight stent-graft. Computed tomography and/or intraarterial angiography were performed during an average follow-up of 10 months (2-18 months). RESULTS: Primary success rate was 75.9% (22 of 29 patients) and the overall success rate was 79.3% with successful correction of one perigraft leak. Twenty patients (69.0%) had significant coronary artery disease. There were two technical failure cases, the one was tortuous iliac vessel with spasm, the other was disconnection of the stent-graft connecting portion. Complications related to procedure occurred in 13.8% of patients (4 of 29 patients) and two of these four patients had procedure-related mortality because of acute renal failure following contrast overdose and sepsis after operation. CONCLUSIONS: Endovascular treatment of infrarenal AAA with bifurcated stent-graft (Vanguard) is effective, feasible and relatively safe. However, further investigation for the outcome, complication and long-term follow-up are needed.

The Effect of Estrogen Containing Liposome Local Delivery on the Neointimal Hyperplasia in the Rat Carotid Artery Balloon-Injury Model

BACKGROUND AND OBJECTIVES: Estrogen has been reported to inhibit migration and proliferation of vascular smooth muscle cells in vitro and in vivo. Sustained local delivery represents a potential alternative to systemic administrationbecauseitcan achieve higher tissue drug levels at site of balloon injury avoiding systemic side effects. We investigated the effect and mechanism of nanoparticulate sustained-release carrier system using liposome incorporating 17beta-estradiol (E2) on neointimal formation in rat carotid artery balloon injury model. MATERIALS AND METHODS: 17-estradiol benzoate, egg phosphatidylcholine, cholesterol, polyethyleneglycol-phosphatidylethanolamine were mixed to produce E2 -liposome formula where the final concentrations of lipids and E2 were 10 mg/ml and 66 M, respectively. The size of the particle was less than 200 nm. Rat carotid artery balloon injury model was used with Sprague-Dawley rats weighing 350+/-30g. Rats were divided into 3 groups of saline (n=22), liposome (n=46) and E2-liposome (n=46) and received 0.2 ml of each agent at injured site. 1) Rats from all groups were sacrificed at 7 (n=4), 14 (n=6), and 21 (n=12) days after injury, respectively. Morphometric analysis was performed for calculating medial area, neointimal area and I/M (intimal area/medialarea)ratio2)Rats from liposome and E2-liposome group sreceived 100mg/kg of 5-bromo-2'-deoxyuridine (BrdU) at 25, 9 and 1hr before sacrifice at 1 (n=4), 3 (n=4), 7 (n=4), and 14 (n=4) days after injury. BrdU and proliferating cell nuclear antigen (PCNA) stains were performed to elucidate a mechanism of inhibitory effect of E2. RESULTS: 1) There was no increase in the neointimal area in liposome group compared with saline group at 7, 14, and 21 days after injury, respectively. 2) There was 17%, 30%, and 34% reduction of I/M ratio in E2 -liposome group compared with liposome group at 7, 14 and 21 days after injury, respectively. 3) BrdU and PCNA stain revealed that at day 3, labelling index (LI) of media was lower in E2-liposome than in liposome group (p<0.05), and at day 7, LI of neointima was not significantly different between the two groups despite smaller neointimal area in the E2-liposomegroup. CONCLUSION: Nanoparticulateliposomeformula appears to be biocompatible. Local intraluminal infusion of E2 liposome formula after balloon injury of rat carotid artery significantly decreased neointimal formation. The mechanism seems to be the inhibitory effect on the proliferative response of smooth muscle cells in media at an early stage of injury. This formula appears to show potential for clinical applications in the prevention of neointimal formation following balloon angioplsty.

Follow-up Results of Stent Placement for Extracranial Carotid Artery Stenosis

BACKGROUND AND OBJECTIVES: Carotid artery stenting has evolved as a potential alternative to carotid endarterectomy in patients (pts) with significant carotid artery stenosis. We evaluated the feasibility and long-term outcome of carotid artery stenting in selected pts at high surgical risk. MATERIALS AND METHODS: Between May, 1996 and September 1998 we performed carotid artery stenting at 35 lesions in 25 pts. There were 23 males and 2 fe-males. Mean age was 63.2+/-6.6 (range 54 - 77). Eight four percent (21/25) of the pts had significant coronary artery disease. Sixty four percent (16/25) of the pts had significant peripheral artery lesions. Sixty percent (15/25) of the pts had neurologic symptoms or non-disabling stroke. We used Wallstent in 32 lesions and Palmaz stent in 3 lesions. Carotid stenting was undertaken in 33 internal carotid, 1 common carotid and 1 external carotid lesions. Bil-ateral carotid stenting was undertaken in forty percent (10/25) of the pts. RESULTS: Carotid stenting was successful in all lesions. One patient died due to massive cerebral hemorrhage 3 days after carotid stenting, who had und-erwent stenting as a rescue procedure for failed endarterectomy. One major stroke developed during procedure with partial recovery. For the combined endpoint of strokes and death within 30 days of procedure, the incidence was 8% and 5.7% in terms of pts and procedures, respectively. On follow-up (12+/-7 months), we found neither neurologic complications nor death. Angiographic and/or duplex sonography which were performed at 5.5 month in all (18) eligible pts with 24 lesions revealed no evidence of stent deformity or restenosis ( 50% of diameter stenosis). Mean angiographic stenosis was 20% on follow-up angiography. CONCLUSION: Carotid artery stenting can be performed with high success and low complication rate in pts with significant carotid artery stenosis especially at high surgical risk. Follow-up clinical outcome of average 12 month was good with low restenosis rate.