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 sought to test whether intracardiac echocardiography (ICE) is superior to conventional monitoring in guiding device closure of interatrial communications (atrial septal defect [ASD] and patent foramen ovale [PFO]).Methods and Results—Forty-four patients undergoing device closure of ASD (n=6) or PFO (n=38) were randomized to have the procedure guided by either ICE (group 1; n=22) or by transesophageal echocardiography (TEE) (group 2; n=22). All interventions were completed successfully. In 1 patient from group 2, atrial fibrillation occurred 1 day after device implantation; the patient was successfully cardioverted on the next day. There were no other complications. Fluoroscopy time (FT) (6.0±1.7 minutes versus 9.5±1.6 minutes;P<0.0001) as well as procedure time (PT) (33.4±4.7 minutes versus 37.8±5.6 minutes;P<0.01) were shorter in group 1 than in group 2. Group 2 patients required general anesthesia without (n=19) or with endotracheal intubation (n=3). In contrast, ICE allowed continuous monitoring of the whole procedure, including balloon sizing before device closure, without sedation.Conclusions—ICE is a safe tool to guide device closure of PFO and ASD. Supine patients tolerate ICE better than TEE. ICE reduces FT and PT. ICE seems to be advantageous, especially when long continuous or repeated echocardiographic viewing is required.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Experimental studies indicate that interleukin-6 (IL-6)–related cytokines, signaling via the shared receptor gp130, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs), provide a critical cardiomyocyte survival pathway in vivo. Little is known about the activation of this signaling pathway in the myocardia of patients with end-stage dilated cardiomyopathy (DCM).Methods and Results—We performed a comprehensive expression and activation analysis of IL-6–related cytokines, receptors, signal transducers, and signal transduction inhibitors in left ventricular (LV) myocardia from patients with DCM (n=10) and non-failing (NF) donor hearts (n=5). Differential expression (DCM versus NF) was observed by immunoblotting at each level of the signaling cascade, including receptor ligands (IL-6: −59%,P<0.01; leukemia inhibitory factor [LIF]: +54%,P<0.05), receptor subunits (LIF receptor: −16%,P<0.05), signaling molecules (the Janus kinase TYK2: −48%,P<0.01; STAT3: −47%,P<0.01), and suppressors of cytokine signaling (SOCS1: +97%,P<0.05; SOCS3: −49%,P<0.01). Tyrosine-phosphorylation status of gp130 was increased (+60%,P<0.05), whereas tyrosine-phosphorylation status of JAK2 was reduced in DCM (−72%,P<0.01). Moreover, as shown by immunohistochemistry, the number of STAT3-positive cardiomyocytes was reduced in DCM (−42%,P<0.01).Conclusion—Signaling via gp130 and JAK-STAT is profoundly altered in DCM. Importantly, tyrosine-phosphorylation of JAK2 is reduced in the face of increased gp130 phosphorylation, indicating impaired downstream activation of this critical pathway in DCM.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Angiostatin is known to inhibit certain aspects of endothelial function, eg, angiogenesis. Here we investigated the effects of angiostatin on another aspect of endothelial function, vasodilation, and examined mechanisms of inhibition—namely, association of heat-shock protein 90 (hsp90) with endothelial nitric oxide synthase (eNOS) and endothelial generation of nitric oxide (·NO) and superoxide anion (&OV0151;). This avenue of investigation was based on recent reports suggesting that hsp90 modulates NOS production of ·NO and &OV0151;.Methods and Results—Effects of angiostatin on vasodilation were determined in arterioles with the use of videomicroscopy in response to endothelium- and ·NO-dependent vasodilators, acetylcholine (ACh) and vascular endothelial growth factor (VEGF), and an endothelium-independent agonist, papaverine. Association of hsp90 with eNOS was determined in rat aortas and bovine aortic endothelial cells (BAECs). Effects of angiostatin on ·NO and &OV0151; generation by BAECs were determined by ozone chemiluminescence and superoxide dismutase (SOD)–inhibitable ferricytochrome c reduction, respectively. Angiostatin impaired vasodilation mediated by ACh and VEGF but not papaverine. Pretreating arterioles with polyethylene glycolated–SOD (PEG-SOD) improved vasodilation to ACh and VEGF. Angiostatin decreased the association of hsp90 with eNOS in aortas and BAEC cultures and increased &OV0151; generation in stimulated BAECs by an L&ggr;-nitroargininemethylester (L-NAME)–inhibitable mechanism.Conclusions—These data indicate angiostatin alters endothelial function by allowing eNOS to generate &OV0151; on activation. Such changes in enzyme function begin to explain, in part, why angiostatin is antiangiogenic and impairs endothelium-dependent vasodilation.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart.Methods and Results—To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142–1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142–1 increased CYP11B2 mRNA expression (1.62±0.12-fold, HS 142–1+AngII 10−7mol/L versus AngII 10−7mol/L alone,P<0.0001). The treatment with exogenous (10−6mol/L) ANP and BNP reduced CYP11B2 mRNA expression (ANP,P=0.0042; BNP,P=0.0012).Conclusions—We showed that endogenous and exogenous natriuretic peptides reduced CYP11B2 mRNA expression in cultured neonatal rat cardiocytes. This may inhibit the cardiac renin-angiotensin-aldosterone system by suppressing the gene expression of CYP11B2 and restraining cardiac hypertrophy and fibrosis.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Risk-stratification scores derived from randomized clinical trial (RCT) data should be evaluated in community-based populations. A simple risk-stratification index for patients with ST-segment elevation myocardial infarction derived from an RCT population was recently proposed, but it has not been validated in a community-based cohort.Methods and Results—We evaluated the simple risk index using data from 49 711 patients ≥65 years of age hospitalized with ST-elevation myocardial infarction. We evaluated the distribution of patients in the 5 simple risk index groups, compared observed and published 30-day mortality rates, and assessed the score’s discrimination and calibration. The simple risk index provided poor discrimination (c=0.62) and calibration (goodness of fitP<0.001) for survival at 30 days. Risk score distribution was skewed, because two thirds (66.1%) of all patients were classified in the highest-risk group, whereas fewer than 11.0% were classified in the 3 lowest-risk groups. Thirty-day mortality estimates were lower than those observed in the cohort (risk group 2 to 5: 1.9% to 17.4% versus 5.3% to 27.9%). Risk index discrimination, calibration, score distribution, and mortality estimates were worse among patients who did not receive acute reperfusion therapy than among those who did.Conclusions—The limited performance of the simple risk index highlights the limitations of applying prognostic models derived in RCT populations to the general population of patients 65 years and older. Prognostic scores must be validated in community-based cohorts before integration into clinical practice.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Heart rate reduction should benefit patients with chronic stable angina by improving myocardial perfusion and reducing myocardial oxygen demand. This study evaluated the antianginal and antiischemic effects of ivabradine, a new heart rate–lowering agent that acts specifically on the sinoatrial node.Methods and Results—In a double-blind, placebo-controlled trial, 360 patients with a ≥3-month history of chronic stable angina were randomly assigned to receive ivabradine (2.5, 5, or 10 mg BID) or placebo for 2 weeks, followed by an open-label 2- or 3-month extension on ivabradine (10 mg BID) and a 1-week randomized withdrawal to ivabradine (10 mg BID) or placebo. Primary efficacy criteria were changes in time to 1-mm ST-segment depression and time to limiting angina during bicycle exercise (exercise tolerance tests), performed at trough of drug activity. In the per-protocol population (n=257), time to 1-mm ST-segment depression increased in the 5 and 10 mg BID groups (P<0.005); time to limiting angina increased in the 10 mg BID group (P<0.05). Deterioration in all exercise tolerance test parameters occurred in patients who received placebo during randomized withdrawal (allP<0.02) but not in those still receiving ivabradine. No rebound phenomena were observed on treatment cessation.Conclusions—Ivabradine produces dose-dependent improvements in exercise tolerance and time to development of ischemia during exercise. These results suggest that ivabradine, representing a novel class of antianginal drugs, is effective and safe during 3 months of use; longer-term safety requires additional assessment.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID