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Vergleichsuntersuchungen zur Restenoserate nach Implantation von antithrombotisch (Hirudin, Iloprost) und/oder antiproliferativ (Dexamethason) beschichteten Stents in der Femoralarterie des Schweines
Vergleichsuntersuchungen zur Restenoserate nach Implantation von antithrombotisch (Hirudin, Iloprost) und/oder antiproliferativ (Dexamethason) beschichteten Stents in der Femoralarterie des Schweines
Restenosis constitutes a serious problem during therapeutical use of stents. It is a multifactorial event composed of inflammatory reactions, thrombus formation, proliferation of muscle cells, and the design of the stent. This study is due to test the influence of various antithrombogenic and/or antiproliferative stent coatings on in-stent restenosis by comparison. Methods: 10 mm InFlow Dynamics Flex-Stents were dip-coated aseptically. Polylactic acid (PLA) is used as a carrier as well as being a testgroup itself. Into this carrier, different pharmaceuticals were incorporated alone or in combination with each other up to 20 % of the PLA concentration. There is around 200 µg of coating material per stent. The groups and their numbers are: PLA (n = 10), IH: 2 % iloprost + 5 % PEG-hirudin (n =11), IHD: 2% iloprost + 5% PEG-hirudin + 5% dexamethasone acetate (n = 11), DD: 5% dexamethasone acetate + 15% dexamethasone (n = 12) and UNC: uncoated bare stents (n = 16) as control group. By random, the stents were implanted into both femoral arteries (one into each) of 30 German Landrace pigs. After four weeks, the animals were euthanised and the stented vessels were analysed at three different levels. The histomorphometrical assessment included the absolute neointimal area, the neointimal thickness, and the thickness of neointima at the struts. Histomorphologically, the mean injury score as well as the symmetry of stent distension were analysed. Results: The biggest trauma of vessel wall was found with the uncoated control stents. The PLA stents showed the most asymmetrical extension, as well as the biggest thickness at the struts and neointimal thickness, and neointimal area. There is no significant difference between the groups. None of the groups is outstanding regarding the reduction of restenosis. Only the uncoated stents are noteworthy having no higher rate of restenosis contrary to expectations. Conclusion: Neither dexamethasone, nor iloprost or hirudin alone or in combination were able to inhibit proliferation of smooth muscle cells. There were no differences regarding neointimal proliferation between the antithrombotics iloprost and hirudin, the antiproliferative substance dexamethasone or the carrier polylactic acid or their combinations.
restenosis, coated stent, animal model, dexamethasone, femoral artery, swine
Rihm, Munhie
2005
Deutsch
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Rihm, Munhie (2005): Vergleichsuntersuchungen zur Restenoserate nach Implantation von antithrombotisch (Hirudin, Iloprost) und/oder antiproliferativ (Dexamethason) beschichteten Stents in der Femoralarterie des Schweines. Dissertation, LMU München: Tierärztliche Fakultät
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Abstract

Restenosis constitutes a serious problem during therapeutical use of stents. It is a multifactorial event composed of inflammatory reactions, thrombus formation, proliferation of muscle cells, and the design of the stent. This study is due to test the influence of various antithrombogenic and/or antiproliferative stent coatings on in-stent restenosis by comparison. Methods: 10 mm InFlow Dynamics Flex-Stents were dip-coated aseptically. Polylactic acid (PLA) is used as a carrier as well as being a testgroup itself. Into this carrier, different pharmaceuticals were incorporated alone or in combination with each other up to 20 % of the PLA concentration. There is around 200 µg of coating material per stent. The groups and their numbers are: PLA (n = 10), IH: 2 % iloprost + 5 % PEG-hirudin (n =11), IHD: 2% iloprost + 5% PEG-hirudin + 5% dexamethasone acetate (n = 11), DD: 5% dexamethasone acetate + 15% dexamethasone (n = 12) and UNC: uncoated bare stents (n = 16) as control group. By random, the stents were implanted into both femoral arteries (one into each) of 30 German Landrace pigs. After four weeks, the animals were euthanised and the stented vessels were analysed at three different levels. The histomorphometrical assessment included the absolute neointimal area, the neointimal thickness, and the thickness of neointima at the struts. Histomorphologically, the mean injury score as well as the symmetry of stent distension were analysed. Results: The biggest trauma of vessel wall was found with the uncoated control stents. The PLA stents showed the most asymmetrical extension, as well as the biggest thickness at the struts and neointimal thickness, and neointimal area. There is no significant difference between the groups. None of the groups is outstanding regarding the reduction of restenosis. Only the uncoated stents are noteworthy having no higher rate of restenosis contrary to expectations. Conclusion: Neither dexamethasone, nor iloprost or hirudin alone or in combination were able to inhibit proliferation of smooth muscle cells. There were no differences regarding neointimal proliferation between the antithrombotics iloprost and hirudin, the antiproliferative substance dexamethasone or the carrier polylactic acid or their combinations.