ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—This study used serial volumetric intravascular ultrasound (IVUS) to evaluate the effect of preinterventional arterial remodeling on in-stent intimal hyperplasia (IH) after implantation of non–polymer-encapsulated paclitaxel-coated stents.Methods and Results—Patients were randomized to placebo or one of two doses of paclitaxel (low dose, 1.28 &mgr;g/mm2; high dose, 3.10 &mgr;g/mm2). Complete preinterventional, post–stent implantation, and follow-up IVUS were available in 18 low-dose and 21 high-dose patients. IH volumes were similar in low-dose and high-dose patients: 17.6±15.1 mm3in low-dose patients and 13.1±13.3 mm3in high-dose patients (P=0.3). Therefore, IVUS findings in low- and high-dose patients were combined. Preinterventional remodeling was assessed by comparing lesion site to proximal and distal reference arterial area: positive remodeling (lesion>proximal reference, n=13), intermediate remodeling (distal reference<lesion<proximal reference, n=13), and negative remodeling (lesion<distal reference, n=13). During follow-up, there was a decrease in lumen volume in positive remodeling lesions (from 106±30 to 90±27 mm3;P=0.0067) and in intermediate remodeling lesions (from 97±28 to 76±31 mm3;P=0.0004), but not in negative remodeling lesions (99±27 versus 92±32 mm3;P=0.15). The follow-up IH volume was lower in negative remodeling lesions (5±7 mm3) compared with positive remodeling (20±14 mm3;P=0.0051) and intermediate remodeling lesions (20±15 mm3;P=0.0043); however, IH volume was virtually identical in positive and intermediate remodeling lesions. Multivariate linear regression analysis determined that remodeling and inflation pressure were independent predictors of IH volume; variables tested in the model included diabetes, acute coronary syndromes, dose, remodeling, and preinterventional plaque burden.Conclusions—Preinterventional arterial remodeling, especially negative remodeling, influences neointimal hyperplasia suppression after implantation of non–polymer-encapsulated paclitaxel-coated stents.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated.Methods and Results—Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant &agr;-Gal A (agalsidase &bgr;, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients compared with controls. Peak systolic strain rate increased significantly in the posterior wall (radial function) after one year of treatment (baseline, 2.8±0.2 s−1; 12 months, 3.7±0.3 s−1;P<0.05). In addition, end-systolic strain of the posterior wall increased significantly (baseline, 34±3%; 12 months, 45±4%;P<0.05). This enhancement in radial function was accompanied by an improvement in longitudinal function. End-diastolic thickness of the posterior wall decreased significantly after 12 months of treatment (baseline, 13.8±0.6 mm; 12 months, 11.8±0.6 mm;P<0.05). In parallel, myocardial mass decreased significantly from 201±18 to 180±21 g (P<0.05).Conclusions—These results suggest that ERT can decrease left ventricular hypertrophy and improve regional myocardial function.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The current method of analyzing myocardial cell transplantation relies on postmortem histology. We sought to demonstrate the feasibility of monitoring transplanted cell survival in living animals using molecular imaging techniques.Methods and Results—For optical bioluminescence charged-coupled device imaging, rats (n=20) underwent intramyocardial injection of embryonic rat H9c2 cardiomyoblasts (3×106to 5×105) expressing firefly luciferase (Fluc) reporter gene. Cardiac bioluminescence signals were present for more than 2 weeks with 3×106cells: day 1 (627 000±15%), day 2 (346 100±21%), day 4 (112 800±20%), day 8 (78 860±24%), day 12 (67 780±12%), and day 16 (62 200±5% p · s−1· cm2−1· sr−1). For micro–positron emission tomography imaging, rats (n=20) received cardiomyoblasts (3×106) expressing mutant herpes simplex type 1 thymidine kinase (HSV1-sr39tk) reporter gene. Detailed tomography of transplanted cells is shown by 9-(4-[18F]-fluoro-3hydroxymethylbutyl)guanine ([18F]-FHBG) reporter probe and nitrogen-13 ammonia ([13N]-NH3) perfusion images. Within the transplanted region, there was a 4.48±0.71-fold increase of in vivo [18F]-FHBG activity and a 4.01±0.51-fold increase of ex vivo gamma counting compared with control animals. Finally, the in vivo images of cell survival were confirmed by ex vivo autoradiography, histology, immunohistochemistry, and reporter protein assays.Conclusions—The location(s), magnitude, and survival duration of embryonic cardiomyoblasts were monitored noninvasively. With further development, molecular imaging studies should add critical insights into cardiac cell transplantation biology.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure.Methods and Results—Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150±160 pg/mL, mean±SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137±124 pg/mL, mean±SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8±3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8±3.0 pg/mL (SEM) (−17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor &bgr;-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs.Conclusions—Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment.Methods and Results—An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy.Conclusions—This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID