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Biomedical subjects

Julian Gunn

Publications and source records attributed to Julian Gunn.

9 recordsLinked to original sources
PubMed2007

Simultaneous kissing stent technique to treat left main stem bifurcation disease.

BACKGROUND: While several endovascular techniques have been developed for treating arterial bifurcation lesions, there is, as yet, no single, widely accepted technique for treating left main stem (LMS) bifurcation lesions with stents. The simultaneous kissing stent (SCS) technique seems particularly suited for such lesions. The authors describe a consecutive cohort of patients with LMS bifurcation stenosis treated with this technique and present mechanistic insights from a porcine model. METHODS: Thirty consecutive patients with LMS bifurcation stenosis +/- multivessel disease were treated with SCS technique using paclitaxel-eluting stents. The technique involves simultaneous implantation of two stents (LMS-LAD and LMS-Cx) so that the proximal end of both stents lie at the same level in the body of LMS. Symptom status was recorded and follow-up angiography was performed. In addition, four pigs underwent SCS implantation of the LMS and were studied by direct examination, histology, and scanning electron microscopy. RESULTS: The patients' mean age was 63, 26 were elective and 19 were male. Paclitaxel-eluting stents (Taxus, Boston Scientific) were used. There was one in-hospital death in a highly unstable patient. At 6-month follow-up angiography, two patients required target lesion revascularization. At 13 +/- 3 month follow-up, the remaining patients remain well, with no other major adverse cardiac events. The animals all survived with patent stents. SEM demonstrated full re-endothelialization and histology showed a thin but complete neointima covering the stent struts. CONCLUSION: The SCS technique for treating LMS bifurcation disease with paclitaxel-eluting stents is safe and feasible. Medium term clinical and angiographic results are good. An endothelium and a thin neointima cover the metal struts.

Aged↗
PubMed2007

Increased in-stent stenosis in ApoE knockout mice: insights from a novel mouse model of balloon angioplasty and stenting.

OBJECTIVE: We aimed to develop and validate a model of angioplasty and stenting in mice that would allow investigation of the response to stent injury using genetically modified mouse strains. METHODS AND RESULTS: Aortic segments from either C57BL/6 wild-type or atherosclerotic ApoE-KO mice underwent balloon angioplasty alone or balloon angioplasty and stenting with a 1.25x2.5 mm stainless steel stent. Vessels were carotid-interposition grafted into genetically identical littermate recipients and harvested at 1, 7, 14, or 28 days. In wild-type mice, stenting generated an inflammatory vascular injury response between days 1 to 7, leading to the development of neointimal hyperplasia by day 14, which further increased in area by day 28 leading to the development of in-stent stenosis. Uninjured vessels and vessels injured by balloon angioplasty alone developed minimal neointimal hyperplasia. In stented ApoE-KO mice, neointimal area at 28 days was 30% greater compared with wild-type mice. CONCLUSIONS: By reproducing important features of human stenting in atherosclerotic mice, we provide the potential to investigate molecular pathways and evaluate novel therapeutic targets for stent injury and restenosis.

Angioplasty, Balloon↗
PubMed2005

Interleukin-1 receptor antagonist alters the response to vessel wall injury in a porcine coronary artery model.

OBJECTIVE: To determine the influence of IL-1 on the arterial response to experimental injury in porcine models of percutaneous coronary intervention (PCI). METHODS: An intravenous (i.v.) bolus of 0.5 mg/kg followed by a subcutaneous (s.c.) infusion of 2 mg/kg/24 h of human IL-1 receptor antagonist (IL-1ra) inhibited neutrophil recruitment in response to intradermal IL-1. Using this dose regimen, five groups of pigs were studied: Group 1, oversized balloon angioplasty of 2 coronary vessels (14-day infusion, 28th day sacrifice and analysis); Groups 2, 3, 4, and 5, oversized stenting of 2 coronary vessels (Group 2: 14-day infusion, 28th day analysis; Group 3: 14-day infusion, 14th day analysis; Group 4: 28-day infusion, 28th day analysis; Group 5: 28-day infusion, 90th day analysis). Neointimal area was quantified by standard means. RESULTS: In Group 1, IL-1ra resulted in a 23% decrease in neointimal area (p=0.04); in Group 2, a 34% increase (p=0.001); in Group 3, a 38% decrease (p<0.0001); in Group 4, a 34% decrease (p=0.0004); and in Group 5, a 41% decrease (p=0.00001). CONCLUSIONS: IL-1ra was associated with a sustained, significant reduction in neointima after vessel wall injury as long as it is given for the duration of the stimulation of the IL-1 system, in this case at least 28 days. This suggests that therapies based on the antagonism of IL-1 may modulate the coronary artery response to injury.

Angioplasty, Balloon, Coronary↗
PubMed2004

The influence of physical stent parameters upon restenosis.

In this paper we examine whether the structure, geometry and dimensions of coronary stents influence the occurrence of restenosis. Whilst many consider these parameters to be less important since the advent of drug-eluting stents, this view reveals a poor appreciation of the technological development of stents over the last 18 years. Early 'slotted tube' stents were completely inflexible and posed major problems for delivery; and early 'coil' stents had poor radial strength, allowing considerable tissue prolapse. Nowadays, we are used to greatly improved physical stent parameters, which provide better deliverability, visibility, procedural success and scaffolding performance. Many of these physical parameters also impact upon restenosis, even in the current era of drug-eluting stent. In this paper we examine the contribution of mode of expansion (self vs. balloon-expandable), design (coil vs. tube), length and width to restenosis. We also consider the more subtle influence of advanced slotted tube vs. modular design, percent metal coverage, strut thickness, strut shape, surface smoothness and alloy composition.

Angioplasty, Balloon, Coronary↗
PubMed2002

Increased intimal hyperplasia in experimental vein graft stenting compared to arterial stenting: comparisons in a new rabbit model of stent injury.

BACKGROUND: In-stent restenosis due to intimal hyperplasia is an important clinical problem. Animal models of stent injury are limited by inconsistent arterial responses to stenting, and less intimal hyperplasia than diseased human vessels. To address these issues, we aimed to compare the degree of intimal hyperplasia in stented rabbit jugular-carotid interposition grafts (vein grafts) versus stented carotid arteries. METHODS: Jugular-carotid vein grafts were constructed in rabbits, then stented or left unstented. Carotid arteries were treated with similar stents or left instrumented only. After 3 or 28 days, vessels were perfusion fixed, embedded in resin, and sections were cut with a diamond saw. Intimal and medial thicknesses were measured in stained sections. RESULTS: After 3 days, inflammatory changes were observed in the intima of all stented vessels. After 28 days, intimal thickness in stented vein grafts was 2-fold greater than in control vein grafts and approximately 4-fold greater than in stented carotid arteries. In addition, the intimal hyperplasia response was markedly more consistent in stented vein grafts compared with stented carotid arteries. CONCLUSIONS: Stent deployment in experimental vein grafts results in increased and more reproducible smooth muscle cell intimal hyperplasia than carotid arterial stenting. This is a promising small-animal model for investigating the intimal response to stenting.

Anastomosis, Surgical↗
PubMed2002

Angiopeptin-eluting stents: observations in human vessels and pig coronary arteries.

Local drug delivery from polymer-coated coronary stents may reduce the incidence of in-stent restenosis. Angiopeptin, an inhibitor of smooth muscle cell proliferation, may reduce the clinical impact of restenosis. The objectives of this study were to characterize the release kinetics and distribution of angiopeptin-loaded phosphorylcholine (PC)-coated drug delivery (DD) BiodivYsio stents and assess their safety and efficacy at reducing neointima formation. I125-angiopeptin-loaded DD-PC-coated stents were implanted into human saphenous vein segments ex vivo, and I125 angiopeptin was detected in the medial layer at 1 hour. When implanted in pig coronary arteries, I125 angiopeptin was found adjacent to the stent at intervals up to 28 days. No significant amounts were found elsewhere. To assess efficacy, twelve angiopeptin-loaded DD-PC-coated stents, twelve non-loaded DD-PC stents, ten standard PC-coated stents and 8 uncoated stents were implanted into normal porcine coronary arteries. Stents were harvested at 28 days and neointima formation was assessed by computerized morphometry. No adverse tissue reactions were seen with any of the PC-coated stents. No significant differences were seen in neointimal or luminal cross-sectional areas between study groups. Local delivery of I125 angiopeptin into the vascular wall can be achieved using a PC-coated stent. Delivery of angiopeptin from drug delivery PC-coated stents is safe, but does not lead to a significant reduction in neointimal growth at 28 days within the parameters of this study.

Animals↗
PubMed2002

Stenting the stent.

BACKGROUND: Stents are constructed with predefined radial strength which, on occasion, may be insufficient to support a resistant lesion. METHODS: We prospectively assessed the need for, and safety of, implanting a second stent within the first, during the index procedure, in a consecutive series of 500 patients undergoing percutaneous coronary intervention (PCI) by a single operator in the period 1998 2001. The indication was a lesion that appeared angiographically suboptimal after full balloon/stent expansion to high pressure with appropriate sizing. Visible thrombus was an exclusion. Stents were slotted tubes or ring designs whenever possible. Clinical follow-up was > 1 year and angiographic re-study was performed when indicated. RESULTS: We identified 18 patients/lesions (3.6%) that required implantation of a stent within a stent. The appearance was due to tissue/stent prolapse in 72%, edge dissection in 17%, narrow stent inflow/outflow in 5.5% and inadvertent stent detachment in 5.5%. There were no lesion-related acute or in-hospital complications. There was no late thrombosis or death. Follow-up was 21 10 months, and revealed 11% target lesion revascularization, of which half were at the site of stent overlap. CONCLUSION: Stenting the stent, where extra support is required, is safe and effective.

Adult↗