Cardiovascular radiation medicine最新文献

Purpose

Based on our preclinic studies with autologous unfractionated bone marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in patients with chronic stable angina was designed. The objectives were to evaluate safety, tolerance and feasibility.

Methods and materials

A multicenter prospective study with inclusion and exclusion criteria defined by an Independent Clinical Committee was carried out. Fourteen patients underwent transcoronary sinus administration of freshly aspirated and filtered AUBM (60–120 ml). Safety and tolerance were evaluated. Feasibility was evaluated with Seattle Angina Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina classification (baseline–Day 180), myocardial perfusion (baseline–Day 90) with independent core laboratory and coronary angiography (baseline and Day 30).

Results

There were no changes in the safety and tolerance parameters. Preliminary clinical efficacy at Day 180 disclosed a significant improvement of 38%, evaluated by the SAQ. The CCS angina classification shows that the mean angina class was 3.0±0.55 at baseline and improved to 2.0±0.00 at Day 180 (P<.001). Semiquantitative radionuclide perfusion imaging (core lab) showed a significant improvement at Day 90 in 13/14 patients, with a mean improvement of 24% at rest (P<.01) and 33% at stress (P<.05). Coronary angiography showed more collateral vessels in 9/14 patients.

Conclusions

We can conclude that AUBM via coronary sinus with transitory occlusion is tolerable and safe. Significant improvement in the myocardial perfusion at Day 90 and in the quality of life at Day 180 was observed.

Here we review PPARγ function in relation to human adipogenesis, insulin sensitization, lipid metabolism, blood pressure regulation and prothrombotic state to perhaps provide justification for this nuclear receptor remaining a key therapeutic target for the continuing development of agents to treat human metabolic syndrome.

Background

The effectiveness of coronary radiation therapy for the treatment of in-stent restenosis (ISR) has been established in several randomized clinical trials. The efficacy of this treatment in the general population is less well established.

Methods and materials

We report our experience in 118 consecutive patients with nonselected high-risk ISR who had undergone successful percutaneous coronary intervention and brachytherapy with ³²P β-irradiation and who were prospectively enrolled in a quantitative angiographic and clinical follow-up protocol at 7 months after the index procedure. The aim of this study was to investigate the independent predictor of angiographic restenosis after ³²P brachytherapy treatment.

Results

Of the patients, 28.8% were diabetics. The mean lesion and mean radiated lengths were, respectively, 30.1 ± 17.2 and 43.8 ± 16.9 mm. The ISR pattern was diffuse in 96% of the treated lesions; in particular, 22.1% presented an occlusive pattern and 37.1% a proliferative pattern. At follow-up angiographic, restenosis and major adverse cardiac events (MACE) rates were, respectively, 20.8% and 29.6%. The univariate predictors of angiographic restenosis were procedural geographic miss, pattern IV ISR, manual pullback maneuver of the radiation source, preprocedural lesion percentage stenosis and preprocedural lesion MLD. At logistic regression analysis, only geographic miss and pattern IV ISR were independent predictors of post intracoronary radiation therapy (IRT) angiographic restenosis.

Conclusion

These data indicate that 7-month angiographic restenosis after ³²P IRT in complex patients with ISR is not a frequent event and is predicted mainly by an occlusive lesion at baseline and by procedural geographical miss.

Purpose

Endovascular irradiation inhibits neointimal hyperplasia in ballooned and stented arteries but impacts both diseased and adjacent normal tissue. Little is known about the effects of irradiation on downstream vasculature. In this study, we investigated vascular function and structure of pig coronary arteries distal to sites of endoluminal irradiation.

Materials and methods

Vasomotor responses of distal arteries to contraction of KCl and PGF_2α and endothelium-dependent (substance P and A23187) and -independent (sodium nitroprusside) relaxation were studied in naı̈ve, sham-treated, irradiated, stented, and stented plus irradiated vessels. Light and scanning electron microscopy were used to assess vascular morphology.

Results

Relaxations to substance P and A23187 at 1 month post treatment were significantly decreased in the irradiated group, whereas contractile response to PGF_2α was significantly increased. Hemorrhage, mural thrombus, and inflammation were present at the upstream-irradiated site; inflammatory cells were also present adherent to the endothelium in the distal segments.

Conclusions

Distal vasomotor function reflects an influence from the nature of a proximal intervention. The effect of irradiation on downstream conduit arteries to increase the threshold of contractility and suppress endothelium-dependent relaxation may be related to the presence of inflammatory cells at both the upstream-instrumented site as well as the distal location.

Computed Tomography (Electron Beam Tomography: EBCT and multislice computed tomography: MSCT) have recently emerged as non-invasive diagnostic modalities that can quantify coronary calcium which is not only as indicator of coronary risk, but also permits assessment of the coronary lumen. The 16-slice MS-CT, the most recent CT-scanner has a very high resolution, which allows non-invasive assessment of coronary plaques. This has led to a stimulus for further research to assess the role of MSCT coronary plaque imaging in the identification of high-risk coronary plaques.

Background

Despite the fact that in animal models direct stenting (DS) reduces the vessel injury, in clinical practice this treatment strategy did not reduce late restenosis as compared to conventional strategy with balloon predilatation (PD). However, the influence of DS was not evaluated when stent expansion is optimized by intravascular ultrasound (IVUS) assessment.

Methods

We analyzed the in-hospital and 1-year outcomes of patients at Washington Hospital Center who were treated with percutaneous coronary interventions and stent implantation when percutaneous intervention was guided by IVUS. Only patients treated for single de novo lesions were included.

Results

In 1386 patients, 251 (18.1%) were treated with DS and 1135 (71.9%) were treated with PD. Pre- and postprocedure characteristics by angiography and IVUS were similar in both groups. Postprocedure non-Q-wave myocardial infarction (MI) occurred in 4.9% of the DS group and in 12.5% of the PD group (P=.005). At 1-year follow-up, target lesion revascularization (TLR) rate was 4.9% in the DS group and 14.8% in the PD group (P=.005). DS strategy (odds ratio=.46, confidence interval=.25–.85, P=.013) was independently correlated to lower risk for revascularization in multivariate analysis.

Conclusion

When DS is implemented by IVUS assessment, it is associated with low in-hospital and long-term events.

Purpose

To report follow-up results of a prospective trial on centered endovascular gamma-irradiation (CEGI) after percutaneous transluminal angioplasty (PTA) for stenosis of arteriovenous fistula in hemodialysis patients.

Methods and materials

Eight patients receiving PTA for recurrent (n=4) or de novo arteriovenous fistula stenoses were treated with CEGI with iridium-192 (14 Gy). Angiography was performed after 6 and 12 months or if problems reoccurred during hemodialysis. Parameters of hemodialysis and duplex sonography were determined the day before and after PTA and after 1, 3, 6, 9, and 12 months.

Results

CEGI was performed successfully and without complications in seven patients. In six patients, restenosis occurred 6–52 weeks (mean 20.8±17.9 weeks) after PTA and required PTA. Parameters of hemodialysis and duplex sonography deteriorated during follow-up.

Conclusions

Centered endovascular gamma-irradiation with iridium 192 immediately after PTA of fistula stenoses was a safe and feasible method but did not prevent restenosis.

Introduction

At the sites of vascular injury, activated and aggregating platelets release small vesiculated structures called platelet microparticles (PMPs). Apart from PMPs they also release several vasoactive mediators including serotonin and thromboxane A₂ (TXA₂). PMPs, serotonin, and TXA₂ have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Thus, this study is designed to examine the interaction between PMPs and serotonin or TXA₂ in inducing rabbit VSMC proliferation.

Methods

Growth-arrested rabbit SMCs were incubated in serum-free medium with different concentrations of PMPs with or without serotonin or TXA₂. VSMC proliferation was examined by increase in incorporation of [³H]thymidine into DNA and by increase in cell number.

Results

PMPs stimulated DNA synthesis in a dose-dependent manner; up to an added concentration of 30 μg/ml (1489±90%) they stimulated SMC proliferation in a logarithmic fashion. Serotonin at 50 μM (345±21%) and TXA₂ at 7.5 μM (900±36%) had their maximal effect. When added together, PMPs (10 μg/ml) and serotonin (5 μM), synergistically induced DNA synthesis (581±36% and 211±11% when added alone and 1201±95% when added together), whereas PMPs (10 μg/ml) and TXA₂ (5 μM) additively induced DNA synthesis (581±36% and 781±56% when added alone and 1262±115% when added together). These increases in DNA synthesis were paralleled by increase in cell number.

Conclusion

PMPs, serotonin, and TXA₂ are mitogenic to SMC, and function as amplification factors to each other, suggesting that inhibition of neointimal proliferation after vascular injury may require the combined use of multiple growth factor inhibitors to simultaneously block several critical cellular activation pathways.

Objective

Endovascular brachytherapy, delivered by a variety of catheter-based devices, has proven clinically effective for the inhibition of neointimal hyperplasia (NIH) after coronary and peripheral balloon/stent angioplasty. No platform, however, has been developed to deliver low-dose radiation in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular response following balloon injury to the rabbit carotid artery, with and without topical low-dose ⁴⁵Ca, applied by an external vascular “wrap”.

Methods

Twelve rabbit carotid arteries were subjected to balloon injury by embolectomy catheter. The common carotid artery was then “wrapped” circumferentially with a biostable polyurethane membrane (Nanoskin Secant Medical, Perkasie, PA), without radiation (n=6), or with radiation (n=6) (⁴⁵Ca ∼50 μCi). The animals were sacrificed at 4 weeks for histologic assessment of the treated vessels.

Results

The ⁴⁵Ca wrap inhibited NIH evidenced by trends towards reduction of intimal area (0.46±0.19 control carotid vs. 0.35±0.15 ⁴⁵Ca-treated carotid arteries; P=.11), maximal intimal thickness (0.21±0.08 vs. 0.16±0.05; P=.12), average intimal thickness (0.12±0.06 vs. 0.08±0.03; P=.08), marginally significant reduction in percent area stenosis (33±15% vs. 21±9%; P=.06) and marked neointima suppression in areas immediately adjacent to ⁴⁵Ca wrap remnants. Medial necrosis (P=.003), however, was observed slightly more for ⁴⁵Ca-treated carotid arteries versus control arteries.

Conclusion

Low-dose ⁴⁵Ca beta-radiation labeled onto a polyurethane membrane appears to inhibit NIH in an animal model.