PURPOSE: Due to thromboembolic complications and in-stent-stenosis after flow diverter (FD) treatment, the long-term use of dual antiplatelet treatment (DAPT) is mandatory. The tested nano-coating has been shown to reduce material thrombogenicity and promote endothelial cell proliferation in vitro. We compared the biocompatibility of coated (Derivo Heal) and non-coated (Derivo bare) FDs with DAPT in an animal model. METHODS: Derivo® bare (n = 10) and Derivo® Heal (n = 10) FD were implanted in the common carotid arteries (CCAs) of New Zealand white rabbits. One additional FD, alternately a Derivo bare (n = 5) or Derivo Heal (n = 5), was implanted in the abdominal aorta (AA) for assessment of the patency of branch arteries. Histopathological examinations were performed after 28 days. Angiography was performed before and after FD implantation and at follow-up. RESULTS: Statistical analysis of the included specimens showed complete endothelialization of all FDs with no significant differences in neointima thickness between Derivo® bare and Derivo® Heal (CCA: p = 0.91; AA: p = 0.59). A significantly reduced number of macrophages in the vessel wall of the Derivo Heal was observed for the CCA (p = 0.02), and significantly reduced fibrin and platelet deposition on the surface of the Derivo Heal was observed for the AA. All branch arteries of the stented aorta remained patent. CONCLUSION: In this animal model, the novel fibrin-based coated FD showed a similar blood and tissue compatibility as the non-coated FD.
Valsartan has the potential to attenuate neointimal hyperplasia and to suppress the inflammatory response. This study aimed to evaluate the role of valsartan in neointimal hyperplasia and the toll-like receptor 4 (TLR4)-nitric oxide synthase (NOS) pathway in the balloon-injured rat aorta.Forty-eight Wistar rats were randomly allocated to three groups: sham control (control), balloon-injured group (surgery), and balloon-injured+valsartan-treated group (valsartan). Rats were killed at 14 and 28 days after balloon-injury, and then the aortic tissues were collected for morphometric analysis as well as for measurements of the mRNA or protein expression of angiotensin II, angiotensin II type 1 (AT1) receptor, angiotensin II type 2 (AT2) receptor, TLR4, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), serine/arginine-rich splicing factor 1(SRSF1) and extracellular signal regulated kinase (ERK). Valsartan at a dose of 20 mg/kg/day markedly decreased neointimal hyperplasia in the aorta of balloon-injured rats, and significantly reduced the mRNA or protein expression of TLR4, AT1 receptor, SRSF1 and phosphorylated-ERK (p-ERK) as well as the aortic levels of iNOS (all p < 0.05). Moreover, valsartan increased the eNOS level and AT2 receptor mRNA and protein expression levels (all p < 0.05). Valsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4-iNOS-ERK-AT1 receptor pathway in the balloon-injured rat aorta.
- MeSH
- Aorta drug effects enzymology pathology MeSH
- Angiotensin II Type 1 Receptor Blockers pharmacology MeSH
- Extracellular Signal-Regulated MAP Kinases metabolism MeSH
- Phosphorylation MeSH
- Hyperplasia MeSH
- Disease Models, Animal MeSH
- Aortic Diseases drug therapy enzymology genetics pathology MeSH
- Neointima * MeSH
- Vascular System Injuries drug therapy enzymology genetics pathology MeSH
- Rats, Wistar MeSH
- Receptor, Angiotensin, Type 1 genetics metabolism MeSH
- Serine-Arginine Splicing Factors metabolism MeSH
- Signal Transduction MeSH
- Nitric Oxide Synthase Type II metabolism MeSH
- Toll-Like Receptor 4 genetics metabolism MeSH
- Valsartan pharmacology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
AIMS: Transradial catheterization (TRC) is a dominant access site for coronary catheterization and percutaneous coronary interventions (PCI) in many centers. Previous studies reported higher intimal thickness of the radial artery (RA) wall in patients with a previous history of TRC. In this investigation the aim was to assess the intimal changes of RA using the optical coherence tomography (OCT) intravascular imaging in a serial manner. METHODS AND RESULTS: 100 patients with the diagnosis of non-ST-elevation myocardial infarction (nSTEMI) treated by PCI were enrolled (6 patients were excluded from this analysis because of occluded RA at follow-up [2 patients] and insufficient quality of OCT images [4 patients]). An 54mm long OCT run of the RA was performed immediately after the index PCI and repeated 9 months later. Volumetric analyses of the intimal layer and lumen changes were conducted. Median intimal volume at baseline versus 9 months was 33.9mm3 (19.0; 69.4) versus 39.0mm3 (21.7; 72.6) (p<0.001); and median arterial lumen volume was 356.3mm3 (227.8; 645.3) versus 304.7mm3 (186.1; 582.7) (p<0.001). There was no significant difference in the effect of any clinical factor on the RA volume changes. CONCLUSIONS: OCT volumetric analyses at baseline and 9 months showed a significant increase in the radial artery intimal layer volume and a decrease in lumen volume after transradial PCI. No significant factors affecting this process were identified.
- MeSH
- Radial Artery diagnostic imaging physiopathology MeSH
- Hyperplasia diagnostic imaging etiology physiopathology MeSH
- Myocardial Infarction diagnostic imaging physiopathology therapy MeSH
- Coronary Angiography adverse effects methods MeSH
- Percutaneous Coronary Intervention adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Neointima diagnostic imaging physiopathology MeSH
- Tomography, Optical Coherence * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Cardiac Catheterization adverse effects MeSH
- Tunica Intima diagnostic imaging physiopathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Incomplete stent apposition and uncovered struts are associated with a higher risk of stent thrombosis. No data exist on the process of neointimal coverage and late apposition status of the bioresorbable vascular scaffold (BVS) when implanted in the highly thrombogenic setting of ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to assess the serial changes in strut apposition and early neointimal coverage of the BVS using optical coherence tomography (OCT) in selected patients enrolled in the PRAGUE-19 study. Intracoronary OCT was performed in 50 patients at the end of primary percutaneous coronary intervention for acute STEMI. Repeated OCT of the implanted BVS was performed in 10 patients. Scaffold area, scaffold mean diameter and incomplete strut apposition (ISA) were compared between baseline and control OCT. Furthermore, strut neointimal coverage was assessed during the control OCT. Mean scaffold area and diameter did not change between the baseline and control OCT (8.59 vs. 9.06 mm(2); p = 0.129 and 3.31 vs. 3.37 mm; p = 0.202, respectively). Differences were observed in ISA between the baseline and control OCT (0.63 vs. 1.47 %; p < 0.05). We observed 83.1 % covered struts in eight patients in whom the control OCT was performed 4-6 weeks after BVS implantation, and 100 % covered struts in two patients 6 months after BVS implantation. Persistent strut apposition and early neointimal coverage were observed after biodegradable vascular scaffold implantation in patients with acute ST-segment elevation myocardial infarction.
- MeSH
- Coated Materials, Biocompatible * MeSH
- Time Factors MeSH
- Everolimus administration & dosage adverse effects MeSH
- ST Elevation Myocardial Infarction diagnostic imaging therapy MeSH
- Cardiovascular Agents administration & dosage adverse effects MeSH
- Coronary Angiography MeSH
- Percutaneous Coronary Intervention adverse effects instrumentation MeSH
- Coronary Vessels diagnostic imaging drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Neointima * MeSH
- Tomography, Optical Coherence MeSH
- Prospective Studies MeSH
- Prosthesis Design MeSH
- Aged MeSH
- Absorbable Implants * MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Study MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: The patency of arteriovenous grafts (AVG) for hemodialysis is mostly limited by growing stenoses that lead to decreasing of blood flow, thromboses and finally to access failure. The aim of this study was to find out if detection of any pathology by duplex Doppler ultrasonography (DDU) early after creation of AVG could identify those with lower survival. METHODS: We retrospectively enrolled AVG examined by DDU in our center within 40 days after their creation during the last 10 years. The findings were divided into 4 subgroups: (1a) normal finding, (1b) DDU risk factor (low flow volume, medial calcinosis of the feeding artery, presence of intimal hyperplasia in the venous anastomosis), (2a) non-significant or (2b) significant stenosis. The primary outcome measure was the cumulative survival of people with AVGs, and the secondary was the primary (unassisted) survival. All patients underwent DDU surveillance every 3 months with pre-emptive treatment of significant stenoses. RESULTS: Overall, 340 cases were found; the median follow-up was 565 days. Normal DDU finding had 60% cases, DDU risk factor 18% cases, non-significant stenosis 13% cases and significant stenosis 9% cases. Occurrence of early significant stenosis was associated with high risk of access loss (hazards ratio (HR) 14.73; 95% CI 5.10-42.58; p < 0.0001). Similarly, the presence of a DDU risk factor and of a non-significant stenosis were related to significantly shorter access lifespan (HR 2.86; 95% CI 1.10-7.40; p = 0.03 and HR 2.83; 95% CI 1.12-7.17; p = 0.03, respectively). CONCLUSION: DDU examination of AVG early after their creation can identify those at higher risk and may contribute to individualize the surveillance strategy.
- MeSH
- Arteriovenous Shunt, Surgical * MeSH
- Blood Vessel Prosthesis * MeSH
- Blood Vessel Prosthesis Implantation MeSH
- Kidney Failure, Chronic therapy MeSH
- Renal Dialysis methods MeSH
- Adult MeSH
- Ultrasonography, Doppler, Duplex MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neointima ultrasonography MeSH
- Graft Occlusion, Vascular ultrasonography MeSH
- Polytetrafluoroethylene MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vascular Calcification ultrasonography MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
A growing body of evidence suggests that the vascular actions of Ang-(1-7) appear to involve increased production of nitric oxide (NO), an important vasodilator, through the activation of MasR, thus indicating the involvement of the MasR in preventing endothelial dysfunction. However, it is unknown whether the MasR could be involved in the progression of the next step in atherosclerosis, neo-intimal formation. To determine whether the deletion of the MasR is involved in the development of intimal thickening in an in vitro model. Mice [three background controls (C57Bl/6) and 3 MasR (-/-)] were killed and the aortas excised and cleaned of connective tissue and cut into 3 mm rings. Rings were placed in an organ culture medium for 5 weeks, embedded in paraffin, cut at 5 μm and stained with haematoxylin and eosin and Masson's trichrome. In addition, aortic reactivity was measured in organ baths. After 5 weeks of culture, the intima:media ratio increased in the aortas from MasR (-/-) mice compared to the control group by 4.5-fold (P < 0.01). However, no significant difference in nuclei area count (cell proliferation) between the MasR (-/-) mice and control group was observed (0.87 ± 0.29% vs. 0.94 ± 0.18%, respectively, P = ns). Functional studies showed only a minor vasoconstrictive and full vasodilative response. This study shows that the deletion of the MasR causes marked increase in the aortic intima:media ratio, which is not due to generalized cellular proliferation. These results provide a functional role for the MasR in atherogenesis.
- MeSH
- Aorta, Thoracic metabolism pathology physiopathology MeSH
- Time Factors MeSH
- Gene Deletion * MeSH
- Phenotype MeSH
- Genotype MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Neointima * MeSH
- Cell Proliferation * MeSH
- Proto-Oncogene Proteins deficiency genetics MeSH
- Receptors, G-Protein-Coupled deficiency genetics MeSH
- Tissue Culture Techniques MeSH
- Vasodilation MeSH
- Vasoconstriction MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
UNLABELLED: OBJECTVES: We investigated whether tacrolimus (FK506) can inhibit neointimal formation in arterialised vein grafts in rats. METHODS: Lewis iliolumbar veins were implanted into the abdominal aorta of isogeneic rats. Animals in the treatment groups had daily intramuscular injections of tacrolimus at 0.2 mg/kg (group B) and 0.1 mg/kg (Group C), respectively. The control group A had no treatment. Light microscope evaluations of arterialised vein grafts were performed 30 days after operation. We determined the presence of endothelial cells, the thickness of intima and media, and the degree of infiltration by MHC class II positive, CD4 positive, and CD8 positive cells into the adventitia. RESULTS: The intimal thickness in group B (5.0±1.0 µm) was statistically lower (P < 0.05) when compared to group C (7.0±3.0 µm). The intimal thickness in untreated group A (12.7±7.0 µm) was statistically higher (P < 0.01) when compared to both treated groups B and C, respectively. The medial thickness and degree of adventitial infiltration by MHC class II positive, CD8 positive, and CD4 positive cells did not differ between groups. CONCLUSION: Treatment with tacrolimus (FK506) showed a dose dependant inhibition of neointimal hyperplasia in arterialised vein grafts in rats (Tab. 1, Fig. 3, Ref. 22).
- MeSH
- Aorta, Abdominal surgery MeSH
- Hyperplasia MeSH
- Immunosuppressive Agents pharmacology MeSH
- Rats MeSH
- Neointima prevention & control MeSH
- Rats, Inbred Lew MeSH
- Tacrolimus pharmacology MeSH
- Tunica Intima drug effects pathology MeSH
- Veins pathology transplantation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 31 cm
Podstatou výzkumného projektu je zavedení techniky zevního resorbovatelného obalu autotranplantované cévy , který by obsahoval a uvolňoval antiproliferativní látky . Použítím modelu na kryse plánujeme přechod do preklinické a klinické praxe vytvořením nové metody k léčení tzv. vein graft dissease u žilních autologních či allogenních graftů.; The expected outcome of our project is the introduction of a novel technique for a periadventitial polymer-based resorbable system for sustained release of antiproliferative drugs, enveloped around the auto-transplanted vein. We plan to use rats as a suitable model for developing this advanced technique and for its future introduction into pre-clinical and clinical practice to prevent and treat so-called "vein graft disease" occurring in autologous or allogenic vein grafts
- MeSH
- Blood Vessel Prosthesis Implantation MeSH
- Hyperplasia MeSH
- Rats MeSH
- Neointima MeSH
- Sirolimus MeSH
- Check Tag
- Rats MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- angiologie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
