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—A relatively simple, invasive method for quantitatively assessing the status of the coronary microcirculation independent of the epicardial artery is lacking.Methods and Results—By using a coronary pressure wire and modified software, it is possible to calculate the mean transit time of room-temperature saline injected down a coronary artery. The inverse of the hyperemic mean transit time has been shown to correlate with absolute flow. We hypothesize that distal coronary pressure divided by the inverse of the hyperemic mean transit time provides an index of microcirculatory resistance (IMR) that will correlate with true microcirculatory resistance (TMR), defined as the distal left anterior descending (LAD) pressure divided by hyperemic flow, measured with an external ultrasonic flow probe. A total of 61 measurements were made in 9 Yorkshire swine at baseline and after disruption of the coronary microcirculation, both with and without an epicardial LAD stenosis. The mean IMR (16.9±6.5 U to 25.9±14.4 U,P=0.002) and TMR (0.51±0.14 to 0.79±0.32 mm Hg · mL−1· min−1,P=0.0001), as well as the % change in IMR (147±66%) and TMR (159±105%,P=NS versus IMR % change), increased significantly and to a similar degree after disruption of the microcirculation. These changes were independent of the status of the epicardial artery. There was a significant correlation between mean IMR and TMR values, as well as between the % change in IMR and % change in TMR.Conclusion—Measuring IMR may provide a simple, quantitative, invasive assessment of the coronary microcirculation.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background–Preclinical and preliminary clinical data have suggested that tumor necrosis factor-&agr; (TNF&agr;) may play a role in the evolution and progression of heart failure and that inhibition of TNF&agr; may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNF&agr;, in patients with moderate-to-severe heart failure.Methods and Results–One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction ≤35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg (P=0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominalP=0.043).Conclusions–Short-term TNF&agr; antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Abnormal plasma markers of a prothrombotic state have been described in atrial fibrillation (AF), but no such marker has yet been shown to reliably predict future stroke or cardiovascular outcome in AF. We hypothesized that raised plasma levels of von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and/or soluble P-selectin (sP-sel, an index of platelet activation) might predict vascular events in AF.Methods and Results—We measured vWf and sP-sel levels by ELISA in 994 participants receiving aspirin in the Stroke Prevention in Atrial Fibrillation III trial, at study entry or after 3 months, and related these indices to the subsequent incidence of stroke and vascular events. Plasma vWf levels were a significant predictor of both stroke (P=0.03) and vascular events (P<0.001), with the greatest risk for those with the highest levels of vWf. After adjustment for other clinical predictors, the relationship between vWf and stroke became nonsignificant, but vWf remained an independent predictor of vascular events (relative risk, 1.2 [95% CI, 1.0–1.4] per 20 IU/dL increase in vWf;P=0.02). No significant relationships were found between sP-sel levels and outcome.Conclusion—Among patients with AF who received aspirin, raised levels of vWf (endothelial damage/dysfunction) were predictive of stroke and vascular events, but raised sP-sel levels (platelet activation) were not associated with increased cardiovascular risk. Endothelial damage/dysfunction (or vWf itself) may play an important role in the mechanisms behind stroke and cardiovascular outcome among aspirin-treated AF patients and might represent a target for novel therapies or an adjunctive aid to risk stratification in AF.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women’s Ischemia Syndrome Evaluation (WISE) study population.Methods and Results—The WISE sample comprised 589 white and 122 black women who underwent angiography for suspected ischemia. The sample was divided into 3 groups: <20% stenosis (38.7%), 20% to 49% stenosis (24.9%), and ≥50% stenosis (35.3%). The three LOX1 polymorphisms (intron 4/G→A, intron 5/T→G, and 3′ UTR/T→C) were in linkage disequilibrium and thus behaved as a single polymorphism. The frequency of the 3′UTR/T allele was significantly higher in whites than blacks (49% versus 19%;P<0.0001). Among white women, the frequency of the 3′UTR/T allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and 79.2% in the <20%, 20% to 49%, and ≥50% stenosis groups, respectively (&khgr;2trend=6.23;P=0.013). Logistic regression analyses indicated that APOE (odds ratio, 1.90;P=0.007) and LOX1 (odds ratio, 1.67;P=0.025) genotypes were independently associated with the risk of disease and that there was no interaction between the two genes. The 3′UTR/T allele carriers also had significantly higher IgG anti-oxLDL levels than individuals carrying the CC genotype (0.94±0.20 versus 0.86±0.16;P=0.032). Furthermore, our electrophoretic mobility shift assay data show that the 3′UTR polymorphic sequence affects the binding of a putative transcription factor in an allele-specific manner.Conclusions—Our data suggest that common genetic variation in the LOX1 gene may be associated with the risk of coronary artery disease in white women.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—In stable coronary artery disease (CAD), exercise training has well-documented positive effects on arterial endothelial function. NO derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery (LIMA) of patients with stable CAD.Methods and Results—In 17 training patients (T) and 18 control patients (C), endothelium-dependent vasodilation and average peak flow velocity (APV) in response to acetylcholine were measured invasively at study beginning and after 4 weeks in the LIMA. In LIMA tissue sampled during bypass surgery, eNOS expression and content of pospho-eNOS-Ser1177, Akt, and phospho-Akt were determined by Western blot and quantitative reverse transcriptase–polymerase chain reaction. After exercise training, LIMA APV in response to acetylcholine was increased by 56±8% (from +48±8% at beginning to +104±11% after 4 weeks,P<0.001). Patients in T had a 2-fold higher eNOS protein expression (T 1.0±0.7 versus C 0.5±0.3 arbitrary units,P<0.05) and 4-fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium (1.2±0.9 versus 0.3±0.2 arbitrary units,P<0.01). A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels (R=0.80,P<0.05) and between phospho-eNOS and &Dgr; APV (R=0.59,P<0.05).Conclusions—Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity. The change in acetylcholine-induced vasodilatation was closely related to a shear stress–induced/Akt-dependent phosphorylation of eNOS on Ser1177.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID