Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 μmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.
Animals ; Cell Cycle ; drug effects ; Cell Line ; Cell Movement ; drug effects ; Graft Occlusion, Vascular ; drug therapy ; metabolism ; pathology ; Muscle, Smooth, Vascular ; metabolism ; pathology ; Myocytes, Smooth Muscle ; metabolism ; pathology ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats

OBJECTIVETo observe the intervention effect of Leihong Granule (LG) in in-stent restenosis (ISR) after endovascular therapy for lower extremity arterial occlusive diseases (LEAOD).

METHODSRecruited 80 LEAOD patients who successfully underwent endovascular therapy (balloon dilation and stent implantation) were randomly assigned to two groups, the control group and the LG group, 40 in each group. Patients in the control group received basic treatment, while those in the LG group additionally took LG for 3 months. Plasma levels of IL-10, IL-18, CRP, and the intima-media thickness (IMT) of lower extremity artery were observed in the two groups between and after treatment. The rate of stent patency, ABI, intermittent claudication, rest pain, and the incidence of amputation the two groups were recorded and observed in the two groups.

RESULTSIn the control group, serum levels of IL-10, IL-18, CRP, and IMT were significantly higher one month after surgery than before surgery (P < 0.05). There was no significant difference in serum levels of IL-10, IL-18, CRP, or IMT between the two groups before surgery (P > 0.05). These indices were obviously lower in the LG group than in the control group after surgery (P < 0.05). Compared with the control group, the incidence rates of intermittent claudication and the rest pain at 6 months and 12 months after surgery significantly decreased (P < 0.05). The stent patency rate at 6 months and 12 months after surgery, and ABI were significantly higher than those of the control group (P < 0.05). There was no statistical difference in the amputation rate between the two groups (P > 0.05).

CONCLUSIONLG might effectively improve ischemic symptoms of affected limbs possibly through lowering the ISR rate after endovascular therapy for LEAOD through preventing immunosuppressive actions.

Aged ; Aged, 80 and over ; Arterial Occlusive Diseases ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Graft Occlusion, Vascular ; therapy ; Humans ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Phytotherapy ; Stents ; Treatment Outcome

OBJECTIVE: The current study retrospectively evaluated whether the percutaneous N-butyl cyanoacrylate (NBCA) seal-off technique is an effective treatment for controlling the angioplasty-related ruptures, which are irresponsive to prolonged balloon tamponade, during interventions for failed or failing hemodialysis vascular accesses. MATERIALS AND METHODS: We reviewed 1588 interventions performed during a 2-year period for dysfunction and/or failed hemodialysis vascular access sites in 1569 patients. For the angioplasty-related ruptures, which could not be controlled with repeated prolonged balloon tamponade, the rupture sites were sealed off with an injection of a glue mixture (NBCA and lipiodol), via a needle/needle sheath to the rupture site, under a sonographic guidance. Technical success rate, complications and clinical success rate were reported. The post-seal-off primary and secondary functional patency rates were calculated by a survival analysis with the Kaplan-Meier method. RESULTS: Twenty ruptures irresponsive to prolonged balloon tamponade occurred in 1588 interventions (1.3%). Two technical failures were noted; one was salvaged with a bailout stent-graft insertion and the other was lost after access embolization. Eighteen accesses (90.0%) were salvaged with the seal-off technique; of them, 16 ruptures were completely sealed off, and two lesions were controlled as acute pseudoaneurysms. Acute pseudoaneurysms were corrected with stentgraft insertion in one patient, and access ligation in the other. The most significant complication during the follow-up was delayed pseudoaneurysm, which occurred in 43.8% (7 of 16) of the completely sealed off accesses. Delayed pseudoaneurysms were treated with surgical revision (n = 2), access ligation (n = 2) and observation (n = 3). During the follow-up, despite the presence of pseudoaneurysms (acute = 1, delayed = 7), a high clinical success rate of 94.4% (17 of 18) was achieved, and they were utilized for hemodialysis at the mean of 411.0 days. The post-seal-off primary patency vs. secondary patency at 90, 180 and 360 days were 66.7 +/- 11.1% vs. 94.4 +/- 5.4%; 33.3 +/- 11.1% vs. 83.3 +/- 8.8%; and 13.3 +/- 8.5% vs. 63.3 +/- 12.1%, respectively. CONCLUSION: Our results suggest that the NBCA seal-off technique is effective for immediate control of a venous rupture irresponsive to prolonged balloon tamponade, during interventions for hemodialysis accesses. Both high technical and clinical success rates can be achieved. However, the treatment is not durable, and about 40% of the completely sealed off accesses are associated with developed delayed pseudoaneurysms in a 2-month of follow-up. Further repair of the vascular tear site, with surgery or stent-graft insertion, is often necessary.
Aged ; Aneurysm, False/etiology/therapy ; Angioplasty, Balloon/*adverse effects ; Arteriovenous Shunt, Surgical/*adverse effects ; Enbucrilate/*administration & dosage ; Ethiodized Oil/administration & dosage ; Female ; Graft Occlusion, Vascular/etiology/*therapy ; Humans ; Male ; *Renal Dialysis ; Retrospective Studies ; Rupture ; Survival Analysis ; Treatment Outcome ; Ultrasonography, Interventional ; Vascular Patency

BACKGROUND/AIMS: Chronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients. METHODS: A total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay. RESULTS: The GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population. CONCLUSIONS: The IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.
Adult ; Aged ; Arteriovenous Shunt, Surgical/*adverse effects ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; Chi-Square Distribution ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Frequency ; Genotype ; Graft Occlusion, Vascular/blood/ethnology/*genetics/physiopathology ; Humans ; Interleukin-6/blood/*genetics ; Kidney Failure, Chronic/blood/ethnology/genetics/immunology/*therapy ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Phenotype ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Promoter Regions, Genetic ; *Renal Dialysis ; Republic of Korea ; Time Factors ; Treatment Outcome ; Vascular Patency/*genetics

OBJECTIVE: We applied a modified pharmacomechanical thrombolysis (PMT) technique to endovascular treatment of thrombosed arteriovenous (AV) grafts without the use of any mechanical thrombectomy devices. The aim of this study was to evaluate the efficacy of the PMT technique in the treatment of thrombosed AV grafts by analyzing the long-term patency. MATERIALS AND METHODS: Eighty-two patients with thrombosed AV grafts were treated with the PMT technique. AV graft surveillance to detect failing/failed access was followed by endovascular treatment. RESULTS: The technical and clinical success rates were 95% and 95%, respectively. The total number of thrombolysis sessions was 279. A post-intervention primary patency rate was 45% and 22% at 12 and 24 months, respectively. The secondary patency rate was 96% and 91% at 12 and 24 months, respectively. No major complications were noticed. CONCLUSION: The modified PMT technique is effective in endovascular treatment of thrombosed AV grafts.
Adult ; Aged ; Aged, 80 and over ; Angiography ; Angioplasty, Balloon ; *Arteriovenous Shunt, Surgical ; Female ; Graft Occlusion, Vascular/*therapy ; Hemostatic Techniques ; Humans ; Male ; Middle Aged ; Polytetrafluoroethylene ; Proportional Hazards Models ; Radiography, Interventional ; Renal Dialysis ; Retrospective Studies ; Stents ; Thrombolytic Therapy/*methods ; Treatment Outcome ; Vascular Patency

OBJECTIVE: The purpose of this study was to evaluate the fistulographic features of malfunctioning axillary loop-configured arteriovenous grafts and the efficacy of percutaneous interventions in failed axillary loop-configured arteriovenous grafts. MATERIALS AND METHODS: Ten patients with axillary loop-configured arteriovenous grafts were referred for evaluation of graft patency or upper arm swelling. Fistulography and percutaneous intervention, including thrombolysis, percutaneous transluminal angioplasty and stent placement, were performed. Statistical analysis of the procedure success rate and the primary and secondary patency rates was done. RESULTS: Four patients had graft related and subclavian venous stenosis, two patients had graft related stenosis and another four patients had subclavian venous stenosis only. Sixteen sessions of interventional procedures were performed in eight patients (average: 2 sessions / patient) until the end of follow-up. An interventional procedure was not done in two patients with central venous stenosis. The overall procedure success rate was 69% (11 of 16 sessions). The post-intervention primary and secondary patency rates were 50% and 63% at three months, 38% and 63% at six months and 25% and 63% at one year, respectively. CONCLUSION: Dysfunctional axillary loop-configured arteriovenous grafts almost always had subclavian venous and graft-related stenosis. Interventional treatments are helpful to overcome this and these treatments are expected to play a major role in restoring and maintaining the axillary loop-configured arteriovenous loop grafts.
Adult ; Aged ; Angioplasty, Balloon/*methods ; Arteriovenous Shunt, Surgical/*methods ; Blood Vessel Prosthesis Implantation/*methods ; Chronic Disease ; Constriction, Pathologic/therapy/ultrasonography ; Female ; Follow-Up Studies ; Graft Occlusion, Vascular/*therapy/ultrasonography ; Humans ; Kidney Failure, Chronic/*complications/therapy ; Male ; Middle Aged ; *Renal Dialysis ; Subclavian Vein/ultrasonography ; Survival Analysis ; Treatment Outcome ; Vascular Patency

Arteriosclerosis Obliterans ; surgery ; Graft Occlusion, Vascular ; therapy ; Humans ; Lower Extremity ; blood supply ; Stents

OBJECTIVETo assess the patency and complications of the polytetrafluoroethylene (PTFE) graft for hemodialysis access and to summarize the experiences in the treatment of graft occlusions.

METHODSThe clinical data of 30 patients who underwent forearm PTFE graft for hemodialysis access from March 2003 to December 2008 in our hospital were retrospectively analyzed.

RESULTSPatients were followed up for (28.7+/-17.6) months (range: 8-78 months).The peri-operative mortality was zero. Primary patency rate was 70.0% at Year 1 and 56.7% at Year 2. Accumulative secondary patency rate was 90.0% and 80.0%, respectively at Year 1 and Year 2. Postoperative complications included graft thrombosis (n=13, 43.3%), venous anastomosis stenosis (n=1, 3.3%), graft infection (n=2, 6.7%), and edema of the forearm (n=10, 33.3%). Totally 24 graft revisions were performed, including thrombectomy (12 times), thrombectomy and venous anastomosis plasty with artificial patch (4 times), arterial and venous anastomosis plasty with patch (2 times), venous anastomosis angioplasty with a balloon (2 times), new graft hemodialysis access construction in the contralateral arm (1 case), and graft removal (3 cases).

CONCLUSIONSPTFE graft is an important backup hemodialysis access in uremic patients. Proper revision according to different cause of graft occlusions can prolong the service time of the graft.

Adult ; Aged ; Aged, 80 and over ; Arteriovenous Shunt, Surgical ; adverse effects ; Blood Vessel Prosthesis ; Female ; Graft Occlusion, Vascular ; etiology ; therapy ; Humans ; Male ; Middle Aged ; Polytetrafluoroethylene ; Renal Dialysis ; Retrospective Studies

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.
Animals ; Anticholesteremic Agents/administration & dosage ; Azetidines/*administration & dosage ; Coronary Restenosis/diagnosis/drug therapy/*etiology ; *Disease Models, Animal ; Drug Combinations ; Drug Implants/administration & dosage ; Drug-Eluting Stents/*adverse effects ; Female ; Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Simvastatin/*administration & dosage ; Swine ; Treatment Outcome

AIMTo study the effect of inducible nitric oxide synthase (iNOS) gene mediated by retroviral vector on the proliferation of cultured aortic vascular smooth muscle cell (VSMC) of rat and the possibility of iNOS gene therapy for vessel graft restenosis.

METHODSEx vitro VSMC were transfected by different viral titer of viral supernatant. The expression of the retroviral iNOS transgene was examined by RT-PCR and Western blot analysis. Nitric oxide (NO) release from infected cells was determined by Griess reaction. The inhibition of iNOS transgenosis on the proliferation of VSMC was detected by modified MTT assay.

RESULTSmRNA and protein of transferred iNOS gene were detected 48 hours post-gene transfer within the transfected cells. Levels of iNOSmRNA and protein in PLXSN-iNOS infected cells were positively correlated with viral titer of viral supernatant. PLXSN-treated VSMC showed no evidence of iNOS mRNA and protein. Transfection of PLXSN-iNOS into cultured VSMC resulted in a dose-dependent increase in NO production. And iNOS transgenosis significantly inhibited proliferation of VSMC. The inhibition effect was positively correlated with viral titer of viral supernatant.

CONCLUSIONiNOS gene could be quickly and effectively transferred into cultured VSMC by retroviral vector and its expression could significantly inhibit the proliferation of cultured VSMC. Retrovirus-mediated gene transfer of iNOS might play an important role in prevention of restenosis.

Animals ; Cell Proliferation ; Cells, Cultured ; Genetic Therapy ; Genetic Vectors ; genetics ; Graft Occlusion, Vascular ; prevention & control ; Male ; Myocytes, Smooth Muscle ; cytology ; enzymology ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Retroviridae ; genetics ; metabolism ; Transfection