| 1. |
- Baklanov, D. V., et al.
(författare)
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Comparison of transendocardial and retrograde coronary venous intramyocardial catheter delivery systems in healthy and infarcted pigs
- 2006
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 68:3, s. 416-423
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Tidskriftsartikel (refereegranskat)abstract
- We compared two routes for myocardial delivery of therapeutics, transendocardial (TE) delivery with an intramyocardial injection catheter, and retrograde coronary venous (RCV) delivery with a balloon occlusion catheter in the interventricular vein. Methods: TE and RCV injection of 15 mu m, neutron-activatable microspheres was compared in healthy pigs (Group I, n = 3), pigs with a 1-week-old myocardial infarction (MI; group II, n = 5), and pigs with a 2-weeks-old MI (group III, n = 4). The MI was induced by a 1-hr balloon occlusion in the LAD. Both methods were compared in the same animal using different microspheres. The RCV catheter allowed for continuous measurement of distal pressure and 2.5 x 10(6) microspheres were injected in 10 ml at 300 mmHg above balloon occlusion pressure. The TE injections were targeted to the infarct zone and 2.5 x 10(6) microspheres were distributed over 10 injections of 200 mu l. Results: The retention of microspheres decreased with increase in MI age, but was comparable between devices within the groups. RCV delivery resulted in (14.3 +/- 0.9)% microsphere retention in Group I, (10.3 +/- 0.2)% in Group II, and (6.4 +/- 0.1)% in group III (P less than 0.05 versus group I). Microsphere retention after TE was (15.1 +/- 0.7)% in group I, (18.9 +/- 0.6)% in group II, (4.1 +/- 0.1)% in Group III (P less than 0.05 versus groups I and II). The RCV catheter delivered primarily to midventricular, antero-septal segments, whereas TE targeted apical areas predominantly. Conclusions: Delivery efficacy was comparable between devices in each group however RCV targeted midventricular areas whereas TE targeted apical areas.
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| 2. |
- Buehler, Alexandra, et al.
(författare)
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cNGR: A novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo
- 2006
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 26:12, s. 2681-2687
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Previously, the peptide sequence cNGR has been shown to home specifically to CD13/APN (aminopeptidase N) on tumor endothelium. Here, we investigated the feasibility of selective imaging of cardiac angiogenesis using the cNGR-CD13/APN system.METHODS AND RESULTS:CD13/APN induction and cNGR homing were studied in the murine myocardial infarction (MI) model. By real-time polymerase chain reaction (PCR) at 7 days after MI, CD13/APN expression was 10- to 20-fold higher in the angiogenic infarct border zone and the MI area than in non-MI areas. In vivo fluorescence microscopy confirmed specific homing of fluorophore-tagged cNGR to the border zone and MI territory at 4 and 7 days after MI with a local advantage of 2.3, but not at 1 or 14 days after MI. Tissue residence half-life was 9.1+/-0.3 hours, whereas the half-life in plasma was 15.4+/-3.4 minutes. Pulse chase experiments confirmed reversible binding of cNGR in the infarct area. Fluorescent labeled cNGR conjugates or antibodies were injected in vivo, and their distribution was studied ex vivo by 2-photon laser scanning microscopy (TPLSM). cNGR co-localized exclusively with CD13/APN and the endothelial marker CD31 on vessels.CONCLUSIONS:In cardiac angiogenesis endothelial CD13/APN is upregulated. It can be targeted specifically with cNGR conjugates. In the heart cNGR binds its endothelial target only in angiogenic areas.
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| 3. |
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| 4. |
- Mandinov, L., et al.
(författare)
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Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
- 2006
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Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:6, s. H2692-H2697
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Tidskriftsartikel (refereegranskat)abstract
- Stress-induced release of IL-1 alpha and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 +/- 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 +/- 0.57 and 1.47 +/- 0.45 mm in TTM-treated and control animals, respectively (P less than 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P less than 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P less than 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P less than 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.
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| 5. |
- Baklanov, Dmitri V., et al.
(författare)
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Live 3D echo guidance of catheter-based endomyocardial injection
- 2005
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Ingår i: Catheterization and cardiovascular interventions. - : Wiley-Blackwell. - 1522-1946 .- 1522-726X. ; 65:3, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- Local delivery of therapeutic agents into the myocardium is limited by suboptimal imaging. We evaluated the feasibility and accuracy of live 313 echo to guide left ventricular endomyocardial injection. An intramyocardial injection catheter was positioned in the left ventricle in five healthy Yorkshire pigs using fluoroscopy. All other catheter manipulations were performed with live biplane and 3D echo guidance. In each animal, a total of 12 endomyocardial injections (volume, 50-100 mu l) of echo contrast mixed with blue tissue dye were performed. Four injections, 10 mm apart, were directed to three myocardial target zones: the anterior septum at the mitral valve level (zone 1); the posterolateral wall between the heads of the papillary muscles (zone 2); and the apex (zone 3). The injections were aimed to form a transverse line in zones 1 and 2 and an inverted triangular pyramid in zone 3. The animals were sacrificed, the hearts were inspected and the left ventricular endocardium was examined to create a map of injection marks. Success, defined as a visible injection of tissue dye, was 95%, and accuracy, defined as an injection into the target zone, was 83%. There was no significant difference in accuracy between the zones. Live 3D echo can successfully guide endomyocardial injections by accurately targeting specific myocardial zones, verifying catheter apposition and, when combined with echo contrast, providing real-time visualization of injectate deposition. (c) 2005 Wiley-Liss, Inc.
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| 6. |
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| 7. |
- de Muinck, Ebo D., et al.
(författare)
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Progress and prospects: Cell based regenerative therapy for cardiovascular disease
- 2006
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Ingår i: Gene Therapy. - : Nature Publishing Group. - 0969-7128 .- 1476-5462. ; 13:8, s. 659-671
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Forskningsöversikt (refereegranskat)abstract
- Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials.
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| 8. |
- De Muinck, Ebo D., et al.
(författare)
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Protection against myocardial ischemia-reperfusion injury by the angiogenic masterswitch protein PR 39 gene therapy : the roles of HIF1 alpha stabilization and FGFR1 signaling
- 2007
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 9:4, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- PR-39, a proline-arginine-rich angiogenic response peptide, has been implicated in myocardial ischemic reperfusion injury. The present study examined the cardioprotective abilities of PR39 gene therapy. Male C5713146 mice were randomized to intramyocardial injecton of 10(9) p.f.u. adenovirus encoding PR39 (PR39), FGFR1 dominant negative signaling construct (FGFR1-dn), empty vector (EV), or PR39 adenovirus plus 4 mu g of plasmid endcoding a HIF1 alpha dominant negative construct (PR39 + HIF1 alpha-dn). Seven days later, hearts were subjected to 20 min of ischemia (1) and 2 h. reperfusion (R) ex vivo and aortic and coronary flow, left ventricular developed pressure (LVDP), and LVdp/dt were measured. Myocardial infarct (MI) size and cardiomyocyte apoptosis were measured by TTC staining and TUNEL, respectively. PR39 expression was robust up to 14 days after gene transfer and was absent after EV and FGFR1-dn. Hemodynamics showed no differences at baseline, and heart rate remained unchanged in all groups throughout the experiment. After I-R, hemodynamics remained unchanged in PR39 hearts, but deteriorated significantly in the other groups, except for aortic flow, which remained significantly higher in FGFR1-dn than in EV and PR39 + HIF1 alpha-dn (p less than 0.05), although it was lower than in PR39 (p less than 0.05). MI was 8.7 +/- 0.9 % in PR39, 23.8 +/- 1.1 % in FGFR1-dn, 29.9 +/- 2.2% in EV, and 30.8 +/- 2.7 % in PR39 + HIF1 alpha-dn (PR39 vs. other groups: p less than 0.05; FGFR1-dn vs. EV and PR39 + HIF1 alpha-dn: p less than 0.05). In PR39, HIF-1 alpha protein was higher than in FGFR1-dn and EV. Importantly, cotransfection of HlF1 alpha-dn with PR39 completely abolished cardioprotection by PR39. Cardioprotection by PR39 is likely conveyed by protective metabolic and survival responses through HIF1-alpha stabilization and not by angiogenesis, because baseline coronary How was the same in all groups. Abrogation of FGFR1 signaling conveyed an intermediate degree of cardioprotection.
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| 9. |
- Dobrucki, Lawrence W, et al.
(författare)
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Approaches to Multimodality Imaging of Angiogenesis
- 2010
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Ingår i: Journal of Nuclear Medicine. - : The Society of Nuclear Medicine Inc. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 51, s. 66S-79S
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis, defined as the formation of new capillaries by cellular outgrowth from existing microvessels, can be assessed by the evaluation of perfusion, function, and metabolism. However, more recently, novel, noninvasive imaging strategies for the evaluation of molecular events associated with the angiogenic process have been developed.
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| 10. |
- Koppal, Sandeep, et al.
(författare)
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Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 78:1, s. 285-296
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. Methods: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60×0.60×0.70mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. Results: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64±0.2737% versus 9.294±0.1762% (mean±standard error of the mean [SEM]; P<0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81±1.276 s-1 versus 56.94±0.9095 s-1 (mean±SEM; P<0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2=0.92) as well as between cumulative R2* and IPH (R2=0.94). Conclusion: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH.
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