Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model / 전남의대학술지

Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7+/-0.18 mm2 in the AES group vs. 0.4+/-0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8+/-5.06% in the AES group vs. 10.5+/-6.80% in the PES group, p<0.05), and in the fibrin score (0.4+/-0.51 in the AES group vs. 2.7+/-0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model.

Histopathological Comparison among Biolimus, Zotarolimus and Everolimus-Eluting Stents in Porcine Coronary Restenosis Model

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the histolopathogical effects among the biolimus, zotarolimus, and everolimus eluting stent (EES) in the porcine coronary restenosis model. SUBJECTS AND METHODS: Pigs were randomized into three groups in which the coronary arteries (15 pigs, 10 coronaries in each group) had either a biolimus A9 eluting stent (BES, n=10), zotarolimus eluting stent (ZES, n=10) or an EES (n=10). Histopathologic analysis was performed at 28 days after stenting. RESULTS: There were no significant differences in the injury score among the three groups. There was a significant difference in the internal elastic lamina, lumen area, neointima area, percent area stenosis, and the fibrin and inflammation score among the three groups (4.3+/-0.53 mm2, 2.5+/-0.93 mm2, 1.8+/-1.03 mm2, 40.7+/-20.80%, 1.7+/-0.41, 1.4+/-0.72 in the BES group vs. 5.1+/-0.55 mm2, 2.3+/-1.14 mm2, 2.8+/-1.00 mm2, 55.4+/-21.23%, 2.0+/-0.39, 1.6+/-0.76 in the ZES group vs. 4.4+/-0.53 mm2, 1.7+/-1.22 mm2, 2.8+/-1.23 mm2, 64.0+/-26.00%, 1.8+/-0.76, 2.1+/-0.90 in the EES group, respectively). BES is more effective in inhibiting neointimal hyperplasia compared to ZES and EES (p<0.0001). According to the fibrin and inflammation score, BES and EES are more effective in decreasing the fibrin deposition compared to ZES (p<0.001). Moreover, BES and ZES are more effective in reducing the inflammatory reaction compared to EES (p<0.001). CONCLUSION: The result demonstrates that BES shows better histopathological characteristics than ZES and EES at one month after stenting in the porcine coronary restenosis model.

Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model / 전남의대학술지

Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7+/-0.18 mm2 in the AES group vs. 0.4+/-0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8+/-5.06% in the AES group vs. 10.5+/-6.80% in the PES group, p<0.05), and in the fibrin score (0.4+/-0.51 in the AES group vs. 2.7+/-0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model.

Effects of Ramiprilat-Coated Stents on Neointimal Hyperplasia, Inflammation, and Arterial Healing in a Porcine Coronary Restenosis Model

BACKGROUND AND OBJECTIVES: The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model. SUBJECTS AND METHODS: Pigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0x17 mm ramiprilat-coated MAC stent or a 3.0x17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting. RESULTS: There were no significant differences in the injury and inflammation scores between the two groups (1.20+/-0.43 vs. 1.23+/-0.57, p=0.8; and 1.21+/-0.39 vs. 1.25+/-0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110+/-89 vs. 123+/-83, p=0.4) and fibrin scores (0.15+/-0.06 vs. 0.17+/-0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06+/-0.51 mm2 vs. 1.28+/-0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9+/-8.7% vs. 21.8+/-7.2%, p=0.088) in the ramiprilat-coated stent group. CONCLUSION: Although the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.

Effect of a Dual Drug-Coated Stent With Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. MATERIALS AND METHODS: A total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting. RESULTS: There was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120+/-85 cells vs. 159+/-80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16+/-0.34 in the dual-coated stent group vs. 0.25+/-0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55+/-0.8 mm2 in dual-coated stent group vs. 1.40+/-0.86 mm2 in the control stent group, p=0.447). CONCLUSION: Although the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model.

The Effect of Oral Administration of Alpha Lipoic Acid and Alpha Lipoic Acid Coated Stent in Porcine In-Stent Restenosis Model

BACKGROUND AND OBJECTIVES: Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction and preventing atherosclerosis-related diseases. We evaluated the affect of ALA on stent restenosis in a porcine model. MATERIALS AND METHODS: The First experiment: Balloon overdilation injuries were performed in two coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stents were randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group II was the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after stenting in both experiments. RESULTS: The First experiment On histopathologic analysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. The neointimal area was 7.3+/-0.9 mm2 in the control group and 2.2+/-1.1 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 75.9+/-8.5% in the control group and 23.5+/-10.5% in the ALA group (p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantly different between the two groups. The neointimal area was 7.4+/-1.1 mm2 in the control group and 1.4+/-0.8 mm2 in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6+/-10.9% in the control group and 15.6+/-7.6% in the ALA group (p<0.001). CONCLUSION: Both a high dose of oral ALA and ALA coated stents inhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model.

The Long-term Clinical Results of a Platelet Glycoprotein IIb/IIIa Receptor Blocker (Abciximab: ReoPro (R) ) Coated Stent in Patients with Coronary Artery Disease

BACKGROUND: Previously, the inhibition of coronary restenosis with Abciximab (ReoPro (R) ) -coated stent in a porcine model was reported. ReoPro (R) inhibits platelet aggregation, the proliferation of vascular smooth muscle cells and the inflammatory reaction. METHODS: A prospective randomized trial was performed to compare two types of stent for revascularization in the native coronary artery. The primary effective end points were major adverse coronary events (MACE) : cardiac death, acute myocardial infarction, target vessel revascularization (TVR) and restenosis at the 6-month clinical and angiographic follow-ups. RESULTS: One hundred and fifty-five patients were enrolled between August 2001 and June 2003. The mean ages (56.0 +/- 10.0 vs. 56.9 +/- 10.8 years), baseline diameter of stenosis and minimal luminal diameter were no different between the two groups. There was one myocardial infarction and revascularization during the hospital stay in control stent group. During the clinical follow-up there were two myocardial infarctions in control group. Follow-up coronary angiograms were performed in 62.3% (48/77) and 65.4% (51/78) of the coated and control groups, respectively. The diameter of stenosis and late loss were significantly less in the ReoPro (R) -coated stent group compared with the controls (16.4 +/- 5.8% vs. 34.3 +/- 6.1%, p=0.009; and 0.33 +/- 0.28 mm vs. 0.88 +/- 0.41 mm; p=0.002). The restenosis and TVR rates of the ReoPro (R) -coated stent were relatively lower compared with the control stent [14.6% (7/48) vs. 29.4% (15/51), p=0.062; and 9.2% (7/76) vs. 14.7% (11/75) ; p=0.327]. CONCLUSION: A ReoPro (R) -coated stent is safe, and may be effective in the prevention of coronary restenosis.

The Long-Term Clinical Results of a Platelet Glycoprotein IIb/IIIa Receptor Blocker (Abciximab : ReoPro(R)) Coated Stent in Patients with Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The inhibition of coronary restenosis with an Abciximab (ReoPro(R))-coated stent has previously been reported by us. This study investigated the clinical outcomes of patients with acute myocardial infarction (AMI) treated with ReoPro-coated stents. SUBJECTS AND METHOD: A prospective randomized trial was conducted to compare two types of stent for the revascularization in 63 patients [Group I (ReoPro(r)-coated stent):n=32, 53.7+/-11.8 years, 27 male, and Group II (control stent):n=31, 55.4+/-12.1 years, 27 male] with AMI. The primary effective end points were major adverse coronary events (MACE):cardiac death, acute myocardial infarction, target lesion revascularization (TLR), in-stent restenosis and late lumen loss at the 1 year clinical and angiographic follow-ups. RESULTS: Baseline clinical characteristics and diameters of stenosis and the minimal luminal diameters were no different between the two groups. There was one myocardial infarction and revascularization during the hospital stay in group II. Follow-up coronary angiograms were performed in 71.9 (23/32) and 77.4% (24/31) of groups I and II, respectively. The diameter of stenosis and late loss were significantly lower in group I than group II (19.4+/-5.1 vs. 34.8+/-5.9%, p=0.013;and 0.39+/-0.26 vs. 0.89+/-0.45 mm;p=0.008, respectively). However, the restenosis rates were no different between the two groups (21.7 vs. 37.5%, p=0.341). One year clinical follow-ups were possible in 98.4% (62/63), and there were two AMI found in group II, but none in group I. The TLR rates and total MACE of group I were relatively lower compared with group II [12.9 (4/31) vs. 29.0% (9/31);p=0.122 and 12.9 (4/31) vs. 35.5% (11/31), p=0.038, respectively]. CONCLUSION: The ReoPro(R)-coated stent was safe, with no stent thrombosis, and effective in patients with AMI.

The long-term clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (Abciximab: ReoPro(R)) coated stent in patients with coronary artery disease / 대한내과학회지

BACKGROUND: Previously we reported the inhibition of coronary restenosis with Abciximab (ReoPro(R))-coated stent in a porcine model. ReoPro(R) inhibits platelet aggregation, the proliferation of vascular smooth muscle cells and inflammatory reaction. METHODS: We performed a prospective randomized trial to compare two types of stents for the revascularization in native coronary artery. The primary effective end points were major adverse coronary events (MACE): cardiac death, acute myocardial infarction, target vessel revascularization (TVR), restenosis at 6-month clinical and angiographic follow-up. RESULTS: One hundred fifty-five patients were enrolled between Aug, 2001 and Jun, 2003. Mean ages (56.0 +/- 10.0 vs. 56.9 +/- 10.8 years), baseline diameter stenosis and minimal luminal diameter were not different between the two groups. There was one myocardial infarction and revascularization during hospital stay in control stent group. During clinical follow-up, there were two myocardial infarctions in control group. Follow-up coronary angiogram was done 62.3% (48/77) in coated and 65.4% (51/78) in control groups. Diameter stenosis and late loss were significantly less in the ReoPro(R)-coated stent group compared with controls (16.4 +/- 5.8% vs. 34.3 +/- 6.1%, p=0.009; and 0.33 +/- 0.28 mm vs. 0.88 +/- 0.41 mm; p=0.002). The restenosis and TVR rates of ReoPro-coated stent were relatively lower compared with control stent [14.6% (7/48) vs. 29.4% (15/51), p=0.062; and 9.2% (7/76) vs. 14.7% (11/75); p=0.327]. CONCLUSION: A ReoPro(R)-coated stent is safe and may be effective in the prevention of coronary restenosis.

The Inhibitory Effects of Platelet Glycoprotein IIb/IIIa Receptor Blocker-Coated Stent on Neointima Formation and Inflammatory Response in Porcine Coronary Stent Restenosis

BACKGROUND AND OBJECTIVES: Previously, we reported that Abciximab (ReoPro(r))-coated stent inhibited in-stent neointimal hyperplasia. ReoPro(r) is known to suppress vascular inflammation through CD 11b/18 (macrophage-1 receptor). We observed inhibitory effects of neointima formation and inflammatory reaction after stenting in a porcine model. MATERIALS AND METHODS: The surface of the stent was coated with ReoPro(r) by means of plasma polymerization followed by chemical grafting. Stent overdilation injury was performed with control bare stent (Group I, n=13) and ReoPro(r)-coated stents (Group II, n=13) in 26 porcine coronary arteries. Follow-up coronary angiogram and the histopathologic assessments of stented porcine coronary were performed on day 14 (Group I:n=6, Group II:n=6) and day 28 (Group I:n=7, Group II:n=7) after stenting. RESULTS: Pathologic area stenosis was 19.7+/-5.3% in Group I and 15.9+/-3.3% in Group II at day 14, and 33.6+/-27.7% and 22.6+/-6.6%, respectively, at day 28 (p<0.05 at day 28). The ratio of inflammatory cells out of the number of total cells in the neointima was 21.8+/-6.5% in Group I and 22.5+/-11.6% in Group II at day 14, and 27.3+/-18.3% in Group I and 28.6+/-10.7% in Group II at day 28 post stenting (p=NS). And those of the media were 2.89+/-1.13% in Group I and 1.36+/-1.27% in Group II at day 14, and 6.61+/-5.61% and 6.26+/-4.51% at day 28 (p=NS). Fibrinoid materials associated with inflammatory reaction were observed in both groups at days 14 and 28. CONCLUSION: An inflammatory reaction was not suppressed with the use of ReoPro(r)-coated stenting in a porcine stent restenosis model.

The Long-Term Clinical Effects of Heparin-Coated Coronary Stent

BACKGROUND AND OBJECTIVES: A heparin-coated stent has been reported to be effective in the prevention of restenosis in a porcine model. The aim of this study was to compare the long term effects of heparin-coated and bare stents in patients who underwent percutaneous coronary intervention (PCI), with regard to the clinical and angiographic outcomes. SUBJECTS AND METHODS: Thirty patients who underwent PCI at Chonnam National University Hospital between July 1999 and December 2000 were randomly assigned into two groups; Group I had control bare stents (n=15, 15 lesions, 59+/-12 years, 13 males) and Group II heparin coated stents (n=15, 15 lesions, 59+/-11 years, 14 males). Six months following stenting, follow-up coronary angiograms were performed in 24 (80%) patients. The average follow-up period was 22+/-6 months. RESULTS: The initial clinical and angiographic characteristics were no different between the two groups. The reference diameters (Group I; 2.84+/-0.57 mm, II; 3.34+/-0.57 mm), minimal luminal (Group I; 2.37+/-0.60 mm, II; 2.60+/-0.59 mm) and diameter stenosis (Group I; 16.8+/-8.8%, II; 22.6+/-8.6%) following stenting, were no different between the two groups. Subacute stent thrombosis was observed in 1 patient (6.7%) of Group I. On follow-up coronary angiograms, the reference (group I; 2.46+/-0.34 mm, group II; 2.70+/-0.43 mm), minimal luminal diameters (group I; 1.47+/-0.59 mm, group II; 1.64+/-0.80 mm) and diameter stenosis (group I; 39.4+/-25.1%, group II; 40.8+/-26.1%) diameters were also no different, and restenosis was observed in 3 (25%) patients of each group. One cardiac death and 3 target vessel revascularizations were observed in each group during follow-up. CONCLUSION: The heparin-coated coronary stents were not effective in the prevention of coronary stent restenosis.

The inhibitory effect of platelet glycoprotein IIb/IIIa receptor blocker-coated stent on porcine coronary stent restenosis / 대한내과학회지

BACKGROUND: The problems of coronary stent thrombosis and restenosis still remain to be solved.The glycoprotein IIb/IIIa receptor blocker, Abciximab (ReoPro), plays important roles in the treatment of high-risk patient with acute platelet-rich thrombus and in the inhibition of smooth muscle cell proliferation. The aim of this study was to determine whether the use of ReoPro-coated stents could reduce the neointimal formation in a porcine coronary stent restenosis model. METHODS: ReoPro was coated on the surface of stent by means of plasma polymerization followed by chemical grafting. Stent overdilation injury was performed with control bare stent (Group I, n=13), and ReoPro-coated stents (Group II, n=14). Follow-up quantitative coronary angiogram was performed at 4 weeks after stenting and histopathologic assessment were compared in both groups. RESULTS: The diameter stenosis by QCA between two groups was significantly higher in Group I (23+/-5 % vs. 15+/-7 %, p=0.003). On histopathologic examination, no in-stent thrombus was observed. The percent area stenosis was significantly higher in Group I than in Group II (48+/-17 % vs. 30+/-16 %, p=0.01). The area of neoinima was larger in Group I than in Group II (3.2+/-1.2 mm2 vs. 2.0+/-1.0 mm2, p=0.01). By immunocytochemistry, proliferation cell nuclear antigen indices were higher in Group I (4.2+/-2.1 %, vs 2.4+/-1.8 % p=0.03). CONCLUSION: The ReoPro-coated stent is safe and effective in the prevention of in-stent thrombus and restenosis, which may be related with the inhibition of platelet thrombus and neointimal cell proliferation.

The Effects of the Heparin-Coated Maximum Arterial Re-Creation (MAC) Stent on Porcine Coronary Stent Restenosis

BACKGROUND: Stent thrombosis and late restenosis are still major limitations in the clinical use of coronary stenting. Heparin-coated stent may reduce the incidences of stent thrombosis and restenosis. Heparin-coated stents were compared with control stents in a porcine coronary stent restenosis model in order to evaluate the effects of heparin-coated stent on stent restenosis. METHODS: Heparin was coated on a stent by deposition of an ultra-thin polymeric film containing amine groups by means of plasma polymerization. And then stent was immersed in heparin solution. Stent overdilation injury (stent:artery=1.3:1.0) was performed with bare (Group I, n=4) and heparin-coated (Group II, n=5) MAC stents in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) was performed at 4 weeks after stenting. The histopathologic assessments (KERN=*)of stented porcine coronary arteries were compared in between 2 groups. RESULTS: 1)Luminal area of stented artery was 7.05+/-1.25 mm2 in Group I and 7.67+/-2.85 mm2 in Group II, which were not different between two Groups. 2)Histopathologic stenosis of Group I was 35.7+/-13.2%, which was higher than 28.6+/-14.7% of Group II (p<0.05). Ratio of neointima/media was 1.16+/-0.52 in Group I and 0.87+/-0.31 in Group II and neointimal area was higher in Group I than in Group II (3.81+/-1.78 mm2 vs. 2.82+/-1.11 mm2, p<0.05 respectively). 3)PCNA (Proliferating cell nuclear antigen) index of GroupI was 10.0+/-2.2%, which was higher than in Group II (6.8+/-4.0%). CONCLUSIONS: Heparin-coated MAC stent may be effective in the inhibition of neointimal proliferation in a porcine stent restenosis model.