Biomedical subjects

Maryam Shirazi

Publications and source records attributed to Maryam Shirazi.

4 recordsLinked to original sources

PubMed2006

Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and in-stent stenosis in a passive-coated stent.

PURPOSE: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA]) and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2 (bFGF2) could be combined as a stable compound and attached to conventional bare metal stents to hinder thrombus formation and inflammatory reactions of stenting. METHODS: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA-coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks. Histological analysis of the stented arteries was performed after hematoxylin-eosin staining. Tissue factor (TF) staining and scanning electron microscopy (SEM) were performed in animals with acute stent thrombosis. RESULTS: Five of the 6 animals receiving an RG-13577/ATA-coated stent experienced acute stent thrombosis, while no adverse events occurred in the animals of the other 2 groups. Follow-up angiography did not show significant in-stent stenosis in either bare or ATA-coated stents. However, histomorphometry revealed larger neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p<0.05) and outward plaque area (1.56+/-0.34 mm2 versus 0.61+/-0.12 mm2, p<0.05) in ATA-coated stents. Three-dimensional IVUS analysis showed analogous results, with significantly larger neointimal volume and outward plaque volume in ATA-coated stents. There was a slight increase in TF staining around the stent struts, while SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents versus the ATA-coated and bare metal stents. CONCLUSION: RG-13577/ATA-coated stents lead to acute stent thrombosis. The ATA coating alone did not lead to acute events, but resulted in higher neointimal hyperplasia and expansive remodeling. These results underline the importance of preclinical studies before using new coated stents in human arteries.

Animals↗

PubMed2003

Serial intravascular ultrasonographic measurements after implantation of biodegradable polymer-coated stents in porcine coronary arteries.

BACKGROUND: Biodegradable stent coatings provide a potential for local drug delivery at the time of vascular injury, while possible tissue toxicity is avoided through constant degradation, leaving behind a bare metal stent. DESIGN: Serial three-dimensional (3D) intravascular ultrasonographic results on bare Megaflex stents and biodegradable polymer-coated Megaflex stents (Hyper stents) (Eurocor, Bonn, Germany) were compared 1 and 4 weeks after intracoronary implantation in pigs. METHODS: Under general anaesthesia, the left anterior descending and circumflex coronary arteries of domestic pigs were stented with Megaflex and Hyper stents, using right femoral artery access. Control coronary angiography and intravascular ultrasonography (IVUS) were performed 1 and 4 weeks after stent implantation using left femoral artery access and right carotid artery access. After recording of angiographic and IVUS data, the pigs were allowed to recover. RESULTS: The 1- and 4-week IVUS follow-ups revealed less neointima formation with Hyper stents than with Megaflex stents: 1-week intimal volume, 11.8+/-0.93 compared with 15.02+/-4.18 mm3, P=0.065; intimal area, 0.81+/-0.06 compared with 1.1+/-0.16 mm2, P =0.003; maximal intimal thickness, 0.12+/-0.01 compared with 0.14+/-0.02 mm, P =0.049; 4-week intimal volume, 12.4+/-1.77 compared with 27.32+/-12.79 mm3, P =0.016; intimal area, 0.82+/-0.12 compared with 1.95+/-0.65 mm2, P=0.003; and maximal intimal thickness, 0.13+/-0.04 compared with 0.30+/-0.10 mm, P=0.003. CONCLUSIONS: Implantation of biodegradable polymer-coated (Hyper) stents results in significantly less neointima formation 1 and 4 weeks after intracoronary implantation than with bare Megaflex stents. Taking advantage of the good collateralization of femoral and carotid arteries of pigs, the use of different arterial accesses allows serial angiographic and 3D IVUS measurements on neointimal development without sacrificing the animals.

Animals↗

PubMed2003

Inhibition of interleukin-1beta convertase is associated with decrease of neointimal hyperplasia after coronary artery stenting in pigs.

Inhibition of IL-1beta convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1beta convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery (group 1, n = 8), while 8 animals served as untreated controls (group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimal volume (27.3 +/- 11.6 vs. 75.8 +/- 18.4 mm3, p < 0.005) and a decreased maximal percentage area stenosis (36.1 +/- 8.5 vs. 69.0 +/- 8.2%, p < 0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 +/- 0.28 vs. 1.75 +/- 0.94 mm, p < 0.005) and a decreased maximal neointimal area (2.14 +/- 1.29 vs. 5.03 +/- 1.92 mm2, p < 0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimal cells, p < 0.05). The coronary arterial tissue IL-1beta level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 +/- 0.162 vs. 0.463 +/- 0.307 pg/mg protein, p < 0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-1beta production and decreased neointimal apoptosis.

Amino Acid Chloromethyl Ketones↗

PubMed2002

Usefulness of intravascular ultrasound-guided histological measurements after stenting in porcine coronary artery.

BACKGROUND: We evaluated the usefulness of intravascular ultrasound (IVUS) in the non-uniform distribution of in-stent neointimal hyperplasia, comparing macroscopic measurements with IVUS-guided histomorphometry. METHODS: Coronary stenting was performed in 45 left coronaries of 39 pigs, using 18 Tenax (Biotronik Gmbh and Co., Berlin, Germany), 11 bare Genius (Eurocor, Bonn, Germany), 10 polymer-coated Genius (Eurocor) and six Biodivysio Matrix LO (Biodivysio Ltd, Farnham, Surrey, UK) stents. After 4 weeks, coronary angiography and IVUS with automatic pullback were performed. IVUS images were analysed using three-dimensional analysis (EchoPlaque 2; INDEC Systems Inc., Mountain View, California, USA). The stented segments were formalin fixed, embedded in Technovit 9100 and cut to 4-8 microm thick slides. The most diseased in-stent segment was 4.49 +/- 4.54 mm away from the distal stent edge assessed by IVUS. Sections of these segments were stained for histomorphometry. RESULTS: A significant correlation was found between IVUS-guided histomorphometry and three-dimensional IVUS measurements of maximal intimal thickness (r = 0.6985, P < 0.005) and area (r = 0.7736, P < 0.001). Macroscopic measurements resulted in comparable maximal intimal thickness (0.83 +/- 0.43 mm compared with 0.81 +/- 0.46 mm) and area (4.44 +/- 1.73 mm2 compared with 3.45 +/- 1.55 mm2) by IVUS and histomorphometry, respectively. Although stent length, diameter, nominal inflation pressure and time and injury score did not differ between the stents, bare Genius stents resulted in significant smaller neointimal volume compared to Tenax, polymer-coated Genius and Biodivysio stents: 24.46 +/- 4.98 mm3 compared with 59.18 +/- 26.41, 60.46 +/- 10.03 and 61.41 +/- 16.27 mm3, respectively (P < 0.05). CONCLUSION: The significant correlation between IVUS-guided histomorphometry and IVUS measurements confirms the usefulness of IVUS in evaluation of experimental in-stent restenosis. Implantation of bare Genius stents resulted in significant lower neointimal hyperplasia compared to Tenax, polymer-coated Genius or phosphorylcholine-coated Biodivysio stents.

Animals↗