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Prevention of intimal hyperplasia after balloon angioplasty and / or stent insertion. or How to mend a broken heart - Just say NO.

Harnek, Jan LU (2003)
Abstract (Swedish)
Popular Abstract in Swedish

Ökat antal patienter som lider av kärlsjukdomar behandlas idag med interventionella metoder istället för kirurgi. Dessa metoder populärt kallade ballong sprängningar, kombineras numera oftast med inläggande av ett metallnät (stent) som hjälper till med att förstärka kärlväggen, så den inte skall falla ihop efter ballong vidgningen. Oavsett vilken metod som används, kompliceras behandlingen av nya förträngningar som bildas på samma ställe, så kallad restenos. Symptomgivande restenos efter intervention förekommer 10-30 %. Restenos är till stor del orsakad av skadan på kärlväggen i samband med ballong vidgning. Målet med avhandlingen har därför varit att utvärdera olika metoder, som kan minska... (More)
Popular Abstract in Swedish

Ökat antal patienter som lider av kärlsjukdomar behandlas idag med interventionella metoder istället för kirurgi. Dessa metoder populärt kallade ballong sprängningar, kombineras numera oftast med inläggande av ett metallnät (stent) som hjälper till med att förstärka kärlväggen, så den inte skall falla ihop efter ballong vidgningen. Oavsett vilken metod som används, kompliceras behandlingen av nya förträngningar som bildas på samma ställe, så kallad restenos. Symptomgivande restenos efter intervention förekommer 10-30 %. Restenos är till stor del orsakad av skadan på kärlväggen i samband med ballong vidgning. Målet med avhandlingen har därför varit att utvärdera olika metoder, som kan minska restenos frekvensen, för behandling av kärlsjukdomar. I första hand har vi försökt att minska skadan på kärlväggen genom att använda självutvidgande stentar, som placeras utan föregående ballongvidgning. I andra hand ville vi minimera kärlväggens reaktion efter kärlskada genom att deponera läkemedel lokalt i det vidgade området. Läkemedlet påverkar läkningsprocessen på molekylär nivå. Försöken utfördes i bäckenkärl samt i hjärtats kranskärl på friska grisar under anestesi. 27 grisar blev behandlade i bäckenkärl med och utan ballong dilatationer eller stent inläggningar. Först undersöktes om inläggning av självvidgande stentar åstadkommer mindre reaktion i kärlväggen än ballongvidgning. Därefter undersöktes vilken av 6 vanliga stentar som minst skadade kärlväggens inre cellager (endotelet). Det påvisades att ballongvidgning orsakar uttalad skada. Skadan på kärlväggen undersöktes med svep elektronmikroskopi, som visade att självutlösande stentar med liten väggtäckning bevarade mest av endotelet. Den bästa av dessa stentar blev slutligen jämförd i ett 8 veckors försök med enbart ballong vidgning för att undersöka effekten på restenos. Detta försök visade att restenos efter inläggning av stent utan ballongvidgning var mindre än om stenten kombinerades med ballongvidgning eller om man endast utförde ballongvidgning. I kranskärl utfördes försöken på 49 grisar. Två kranskärl på varje gris vidgades med ballong. Först jämfördes ballong vidgning med vidgning kombinerad med lokal behandling av ett läkemedel som frisätter kväveoxid. Som kontrollkärl användes obehandlade kranskärl i ett område längre ut på samma kärl. I detta försök visades att kväveoxid påverkar tidigare reparations processer i kärlväggen och kraftigt minskade restenosutveckling. I det sista försöket undersöktes den bakomliggande mekanism för kväveoxidens verkan. Vi har kunnat påvisa att effekten av kväveoxid beror på ändringar i endotel och glatt muskel cellernas energiomsättning. (Less)
Abstract
Background: Restenosis is the most frequently occurring adverse event after percutaneous intravascular treatment of atherosclerotic lesions, which limits long-term patency of the intervention. Objective: The aim of the study was to evaluate if minimizing vascular injury during treatment by insertion of self-expanding stents or modifying the reparative mechanisms by local drug delivery can reduce restenosis. Methods: Healthy pigs were used in all experiments. Iliac arteries in twenty-seven pigs were treated by percutaneous transluminal angioplasty (PTA) or insertion of balloon expandable or self-expanding stents with or without previous PTA. Endothelial damage was evaluated by scanning electron microscopy, proliferation of smooth muscle... (More)
Background: Restenosis is the most frequently occurring adverse event after percutaneous intravascular treatment of atherosclerotic lesions, which limits long-term patency of the intervention. Objective: The aim of the study was to evaluate if minimizing vascular injury during treatment by insertion of self-expanding stents or modifying the reparative mechanisms by local drug delivery can reduce restenosis. Methods: Healthy pigs were used in all experiments. Iliac arteries in twenty-seven pigs were treated by percutaneous transluminal angioplasty (PTA) or insertion of balloon expandable or self-expanding stents with or without previous PTA. Endothelial damage was evaluated by scanning electron microscopy, proliferation of smooth muscle cells by histochemistry, and development of intimal hyperplasia by angiography, intravascular ultrasound and histomorphology. Percutaneous transluminal coronary angioplasty (PTCA) was performed in forty-nine pigs. They were divided into five groups according to treatment as follows: only PTCA, PTCA with local delivery of NaCl, PTCA with local delivery of the Nitric Oxide donor 3- morpholino-sydnonimine (SIN-1), and local delivery of a selective guanylate cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3- alpha)quinoxaline-1-one (ODQ) followed by SIN-1. Untreated segments distally to the treated segments served as base-line controls. The specimens were evaluated by histochemistry, biochemical analysis, angiography and histomorphology. Results: The number of proliferating smooth muscle cells (SMCs) in iliac arteries increased 3-fold after PTA compared to insertion of self-expanding stents. Endothelium was better preserved after deployment of self-expanding stents, especially those with circumscribed wall coverage (50%), compared to stents with extensive wall coverage (3-24%), or to balloonexpanded stents (6%), or to balloon dilation only (6%). At 8 weeks following treatment, arteries treated with self-expanding stents without previous PTA had less intimal hyperplasia and larger luminal diameter compared to PTA combined with stent insertion or PTA alone. After PTCA and local deposition of SIN-1, a 54% reduction of restenosis compared to PTCA and 59% reduction compared to PTCA + NaCl was apparent. The expression of nitric oxide synthase (NOS) and the ratio of intermediate filaments (IF) to actin was reduced more than 40% upon treatment with SIN-1. After c-GMP inhibition by ODQ, restenosis increased 2-fold compared to PTCA+NaCl treated arteries while the expression of NOS and the IF/actin ratio did not change compared to PTCA and to PTCA + NaCl treated segments. Conclusions: Direct stenting with self-expanding stents results in reduced SMC proliferation, better preserved endothelium, and lower restenosis rate compared to balloon angioplasty before stenting or balloon angioplasty alone. In coronary arteries the development of intimal hyperplasia can be significantly reduced with site-specific delivery of nitric oxide donor. The pathway for this effect is cGMP dependent. Early changes in NOS expression in the endothelium and the structural protein content of the vascular media are correlated to the development of intimal hyperplasia and restenosis. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Günther, Rolf W, Aachen, Germany
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Kardiovaskulära systemet, Cardiovascular system, Remodeling. Endothelium-derived factors. Self-expanding stents. Restenosis. Scanning -electron microscopy. Endothelial factors. Nitric oxide. Intimal hyperplasia. Angioplasty. Stents. Interventional procedures. Endothelium.
pages
150 pages
publisher
Jan Harnek Hjärtröntgen - HLD - Universitetsjukhuset 22185 Lund,
defense location
BMC- Segerfalkssalen kl 13
defense date
2003-02-07 13:00
ISBN
91-628-5548-4
language
English
LU publication?
yes
id
38e41bd3-beaf-4052-8e50-a499ae156f70 (old id 465377)
date added to LUP
2007-09-18 19:23:35
date last changed
2016-09-19 08:45:04
@misc{38e41bd3-beaf-4052-8e50-a499ae156f70,
  abstract     = {Background: Restenosis is the most frequently occurring adverse event after percutaneous intravascular treatment of atherosclerotic lesions, which limits long-term patency of the intervention. Objective: The aim of the study was to evaluate if minimizing vascular injury during treatment by insertion of self-expanding stents or modifying the reparative mechanisms by local drug delivery can reduce restenosis. Methods: Healthy pigs were used in all experiments. Iliac arteries in twenty-seven pigs were treated by percutaneous transluminal angioplasty (PTA) or insertion of balloon expandable or self-expanding stents with or without previous PTA. Endothelial damage was evaluated by scanning electron microscopy, proliferation of smooth muscle cells by histochemistry, and development of intimal hyperplasia by angiography, intravascular ultrasound and histomorphology. Percutaneous transluminal coronary angioplasty (PTCA) was performed in forty-nine pigs. They were divided into five groups according to treatment as follows: only PTCA, PTCA with local delivery of NaCl, PTCA with local delivery of the Nitric Oxide donor 3- morpholino-sydnonimine (SIN-1), and local delivery of a selective guanylate cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3- alpha)quinoxaline-1-one (ODQ) followed by SIN-1. Untreated segments distally to the treated segments served as base-line controls. The specimens were evaluated by histochemistry, biochemical analysis, angiography and histomorphology. Results: The number of proliferating smooth muscle cells (SMCs) in iliac arteries increased 3-fold after PTA compared to insertion of self-expanding stents. Endothelium was better preserved after deployment of self-expanding stents, especially those with circumscribed wall coverage (50%), compared to stents with extensive wall coverage (3-24%), or to balloonexpanded stents (6%), or to balloon dilation only (6%). At 8 weeks following treatment, arteries treated with self-expanding stents without previous PTA had less intimal hyperplasia and larger luminal diameter compared to PTA combined with stent insertion or PTA alone. After PTCA and local deposition of SIN-1, a 54% reduction of restenosis compared to PTCA and 59% reduction compared to PTCA + NaCl was apparent. The expression of nitric oxide synthase (NOS) and the ratio of intermediate filaments (IF) to actin was reduced more than 40% upon treatment with SIN-1. After c-GMP inhibition by ODQ, restenosis increased 2-fold compared to PTCA+NaCl treated arteries while the expression of NOS and the IF/actin ratio did not change compared to PTCA and to PTCA + NaCl treated segments. Conclusions: Direct stenting with self-expanding stents results in reduced SMC proliferation, better preserved endothelium, and lower restenosis rate compared to balloon angioplasty before stenting or balloon angioplasty alone. In coronary arteries the development of intimal hyperplasia can be significantly reduced with site-specific delivery of nitric oxide donor. The pathway for this effect is cGMP dependent. Early changes in NOS expression in the endothelium and the structural protein content of the vascular media are correlated to the development of intimal hyperplasia and restenosis.},
  author       = {Harnek, Jan},
  isbn         = {91-628-5548-4},
  keyword      = {Kardiovaskulära systemet,Cardiovascular system,Remodeling. Endothelium-derived factors. Self-expanding stents. Restenosis. Scanning -electron microscopy. Endothelial factors. Nitric oxide. Intimal hyperplasia. Angioplasty. Stents. Interventional procedures. Endothelium.},
  language     = {eng},
  pages        = {150},
  publisher    = {ARRAY(0xc47d300)},
  title        = {Prevention of intimal hyperplasia after balloon angioplasty and / or stent insertion. or How to mend a broken heart - Just say NO.},
  year         = {2003},
}