A meta-analysis of 11 randomized trials was done to compare stenting versus balloon angioplasty (BA) in small coronary vessels.Randomized studies on coronary stenting (CS) in small vessels have yielded controversial results.Eleven randomized trials on CS versus BA in small vessels, including angiographic re-evaluation at six months, were analyzed.The BeStent (Medtronic Instent, Minneapolis, Minnesota) was used in four studies, the Multi-Link (Guidant, Advanced Cardiovascular Systems Inc., Santa Clara, California) in three trials, and the NIR (Boston Scientific Corp., Boston, Massachusetts), JoStent (Jomed International AB, Helsingborg, Sweden), Tenax (Biotronik, Berlin, Germany), and BioDivysio (Abbott Vascular Devices, Redwood City, California) in the remaining four trials. Overall, 3,541 patients were included (1,672 allocated to BA and 1,869 to stent). The rate of cross-over from balloon to stent in the pooled population was 19%, and unsuccessful stent deployment occurred in 2% of the patients allocated to stent. The pooled rates of restenosis were 25.8% and 34.2% in patients allocated to stent and balloon, respectively (p = 0.003) (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.65 to 0.92). A smaller reference vessel diameter at baseline was associated with a higher risk reduction in the restenosis rate (y = −3.551 + 1.826 [x]; p = 0.012). Patients allocated to stent had lower rates of major adverse cardiac events (15.0% vs. 21.8%, p = 0.002; RR 0.70; 95% CI 0.57 to 0.87) and new target vessel revascularizations (12.5% vs. 17.0%, p = 0.004; RR 0.75, 95% CI 0.61 to 0.91).Elective stenting is superior to provisional stenting in small coronary arteries. This benefit is more evident in smaller coronary arteries.

This study was conducted to evaluate the endothelialization and the inflammatory responses depending on the administration duration of triple anti-platelet therapy at overlapping bioabsorbable polymer coated biolimus-eluting stents (BESs) in a porcine coronary model.We successfully deployed 36 overlapping BESs for the left anterior descending coronary and left circumflex artery or right coronary artery in 18 non-injured pigs. Total pigs were divided into 3 groups (12 overlapping stents of 6 pigs in each group) as follows: group I received aspirin 100 mg and clopidogrel 75 mg daily for 8 weeks, group II received aspirin 100 mg and clopidogrel 75 mg daily for 8 weeks and cilostazol 200 mg daily for initial 4 weeks, and group III received aspirin 100 mg, clopidogrel 75 mg, and cilostazol 200 mg daily for 8 weeks. Follow-up coronary angiograms and histomorphometric and histopahtologic analyses at overlapping and non-overlapping segments were performed respectively.Inflammation score was similar between overlapping and non-overlapping segments in all pigs (1.2 ± 0.33 vs. 1.1 ± 0.17, p = 0.117). The neointima area (NA) and percent area stenosis (%AS) at overlapping segments were not significantly different among the 3 groups. However, at non-overlapping segments, NA and %AS in group III were significantly smaller than those in group I (2.3 ± 0.50 mm2 vs. 1.8 ± 0.43 mm2, p = 0.037; 48.9 ± 12.85% vs. 37.7 ± 9.08%, p = 0.031).Our study shows that BES appears to be reliable on the inflammatory response at overlapping segments as well as non-overlapping segments. Long-term administration of cilostazol is more effective in reducing neointimal formation at non-overlapping segments of BESs in a porcine coronary model.

904 Pioglitazone attenuates neointima formation and modifies its composition in a balloon-denuded and radiated hypercholesterolemic rabbit R Pakala, C Dilcher , R Baffour, D Hellinga, R Seabron, M Joner , F Kolodgie , R Virmani , R Waksman Washington Hospital Center, Washington, DC, USA, CV Path Org, Gaithersburg, MD, USA

The oxidative modification of low-density lipoprotein (LDL) hypothesis implies that antioxidants should be effective in suppressing atherosclerosis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and irradiated hypercholesterolemic rabbits. Rabbits were fed with a 1% cholesterol diet supplemented with or without a mixture of antioxidants (vitamin E, vitamin C, selenium, zinc, copper, manganese, N-acetylcysteine, glutamine). At 7 days both iliac arteries were balloon denuded, and 4 weeks later, 1 iliac artery underwent endovascular irradiation (n=12), while the contralateral was sham treated (n=12). Four weeks after irradiation, animals were euthanized, and arteries were fixed and processed for histo- or immunohistochemistry for determining the plaque area, macrophage count, and oxidized LDL-positive areas. Plasma antioxidant levels were significantly higher in the animals fed with antioxidant diet. Plasma (thiobarbituric acid-reactive substances) and arterial tissue oxidized LDL (immunoreactive to specific oxidized LDL antibody) levels were significantly higher in the irradiated as compared with nonirradiated animals (0.69+/-0.09 and 31.05+/-4.21 versus 0.24+/-0.04 and 18.42+/-4.62, P<0.001 and 0.05), and antioxidants partially lowered the oxidized LDL levels (0.35+/-0.14 and 25.41+/-4.82, P<0.001 and 0.01). Plaque area in the irradiated animals was 175% greater than in nonirradiated animals (P<0.05). Antioxidant supplementation resulted in a 50% decrease in plaque area of both control and irradiated animals. Antioxidants reduced both the cholesterol-induced and radiation-enhanced circulating and tissue oxidized LDL levels, resulting in reduced plaque.

Purpose/Objective: Ionizing Radiation (IR) promotes development of Atherosclerotic Lesions (ASL). Oxidized lipoproteins are known to be causal agent for induction of ASL. Antioxidants can inhibit lipoprotein oxidation and may reduce ASL formation. This study is designed to test the potential of antioxidants inhibiting IR induced ASL formation in a rabbit model.Materials/Methods: Eighteen rabbits were fed with 1% Cholesterol Diet (CD) and additional 18 were fed with 1% CD plus Antioxidant supplemental Diet (AD) (Vitamins A, C and E, Ions Zn, Se, Mn, and N acetyl-cysteine). One week after start of diet iliac arteries of all animals were balloon denuded. Four weeks after balloon denudation one iliac artery each in 12 animals both in CD group (CD+Rad) and AD group (AD+Rad) was radiated. Six animals both in the CD and in the AD group did not receive IR. The 192Ir source wire was inserted into the lumen catheter. The prescription dose was 15Gy at 2mm from the center of the source. At week 5–8 all rabbits were fed 0.15% CD or 0.15% CD+AD until sacrifice. At 8 weeks animals were sacrificed and morphometric/immunohistochemical analysis of iliac arteries were performed. Macrophages were identified with antibody RAM 11; oxidized LDL with DHL3. A p-value <0.05 is considered to be statistically significant.Results: Radiation significantly increased Plaque Area (PA) independent of Diet (p=0.0006) and AD led to a significant decrease of PA without radiation (p=0.01) (see Figure 1). There was a significant reduction of Lumen Area (LA) due to Radiation in both diet groups (p<0.006). Radiation significantly raised the amount of macrophages in both diet groups (p=0.0002). AD significantly reduced amount of macrophages (p<0.0001). Oxidized LDL was significantly increased by Radiation (p<0.0025). The interaction between radiation and diet never was significant (overall p<0.05).Conclusions: We showed that Antioxidants decrease progression of ASL in non radiated arteries by reducing LDL oxidation (LDLox) and significantly attenuate radiation induced plaque formation. In the present study IR significantly increased amount of macrophages compared to control arteries. We demonstrated that radiation enhances the atherogenic effects of a high-fat diet. We thus propose that radiation promotes short-lived changes in oxidative stress conditions (O2- concentrations) in the artery wall. During time of IR atherogenic lipoproteins, elevated due to high-fat diet, must be available to participate in the initiation of ASL. The results of the study are in conformity with the known theory of radiation induced LDLox: Radiation induces free radical formation and in turn facilitates LDLox. Oxidized LDL attracts inflammatory cells to the injured site secreting proatherogenic cytokines increasing plaque formation. Lipid oxidation by-products present in oxidized lipoproteins have been shown to induce the expression of leukocyte adhesion molecules and to alter the chemotactic behavior of macrophages in a manner expected to promote their retention in the artery wall. Radiation has been shown to promote rapid induction of adhesion molecules (E-selectin, intercellular and platelet endothelial cell adhesion molecule 1). Radiation could thus directly promote inflammation and recruitment of inflammatory cells. AD attenuating LDLox leads to reduced burden of macrophages in the radiation group. In summary, we have presented evidence that IR promotes atherogenesis in rabbits fed a high cholesterol diet. It may underline the critical role of a high fat diet and the requirement of an anti oxidant diet to be given in this setting. Purpose/Objective: Ionizing Radiation (IR) promotes development of Atherosclerotic Lesions (ASL). Oxidized lipoproteins are known to be causal agent for induction of ASL. Antioxidants can inhibit lipoprotein oxidation and may reduce ASL formation. This study is designed to test the potential of antioxidants inhibiting IR induced ASL formation in a rabbit model. Materials/Methods: Eighteen rabbits were fed with 1% Cholesterol Diet (CD) and additional 18 were fed with 1% CD plus Antioxidant supplemental Diet (AD) (Vitamins A, C and E, Ions Zn, Se, Mn, and N acetyl-cysteine). One week after start of diet iliac arteries of all animals were balloon denuded. Four weeks after balloon denudation one iliac artery each in 12 animals both in CD group (CD+Rad) and AD group (AD+Rad) was radiated. Six animals both in the CD and in the AD group did not receive IR. The 192Ir source wire was inserted into the lumen catheter. The prescription dose was 15Gy at 2mm from the center of the source. At week 5–8 all rabbits were fed 0.15% CD or 0.15% CD+AD until sacrifice. At 8 weeks animals were sacrificed and morphometric/immunohistochemical analysis of iliac arteries were performed. Macrophages were identified with antibody RAM 11; oxidized LDL with DHL3. A p-value <0.05 is considered to be statistically significant. Results: Radiation significantly increased Plaque Area (PA) independent of Diet (p=0.0006) and AD led to a significant decrease of PA without radiation (p=0.01) (see Figure 1). There was a significant reduction of Lumen Area (LA) due to Radiation in both diet groups (p<0.006). Radiation significantly raised the amount of macrophages in both diet groups (p=0.0002). AD significantly reduced amount of macrophages (p<0.0001). Oxidized LDL was significantly increased by Radiation (p<0.0025). The interaction between radiation and diet never was significant (overall p<0.05). Conclusions: We showed that Antioxidants decrease progression of ASL in non radiated arteries by reducing LDL oxidation (LDLox) and significantly attenuate radiation induced plaque formation. In the present study IR significantly increased amount of macrophages compared to control arteries. We demonstrated that radiation enhances the atherogenic effects of a high-fat diet. We thus propose that radiation promotes short-lived changes in oxidative stress conditions (O2- concentrations) in the artery wall. During time of IR atherogenic lipoproteins, elevated due to high-fat diet, must be available to participate in the initiation of ASL. The results of the study are in conformity with the known theory of radiation induced LDLox: Radiation induces free radical formation and in turn facilitates LDLox. Oxidized LDL attracts inflammatory cells to the injured site secreting proatherogenic cytokines increasing plaque formation. Lipid oxidation by-products present in oxidized lipoproteins have been shown to induce the expression of leukocyte adhesion molecules and to alter the chemotactic behavior of macrophages in a manner expected to promote their retention in the artery wall. Radiation has been shown to promote rapid induction of adhesion molecules (E-selectin, intercellular and platelet endothelial cell adhesion molecule 1). Radiation could thus directly promote inflammation and recruitment of inflammatory cells. AD attenuating LDLox leads to reduced burden of macrophages in the radiation group. In summary, we have presented evidence that IR promotes atherogenesis in rabbits fed a high cholesterol diet. It may underline the critical role of a high fat diet and the requirement of an anti oxidant diet to be given in this setting.

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC‐based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high‐performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion‐fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 ± 0.84 vs. 4.77 ± 1.71 mm 2 , respectively; P < 0.001). In the porcine coronary model, site‐specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments. Catheter Cardiovasc Interv 2005;64:389–394. © 2005 Wiley‐Liss, Inc.