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Circulation,
Volume 100,
Issue 25,
1999,
Page 2-2
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ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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2. |
Will Blocking the Platelet Save the Diabetic? |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2466-2468
Spencer King,
Ehtisham Mahmud,
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ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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Protection of the Myocardium During Ischemia and ReperfusionNa+/H+Exchange Inhibition Versus Ischemic Preconditioning |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2469-2472
Metin Avkiran,
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ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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4. |
Novel Modulator for Endothelial Adhesion Molecules Adipocyte-Derived Plasma Protein Adiponectin |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2473-2476
Noriyuki Ouchi,
Shinji Kihara,
Yukio Arita,
Kazuhisa Maeda,
Hiroshi Kuriyama,
Yoshihisa Okamoto,
Kikuko Hotta,
Makoto Nishida,
Masahiko Takahashi,
Tadashi Nakamura,
Shizuya Yamashita,
Tohru Funahashi,
Yuji Matsuzawa,
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摘要:
BackgroundAmong the many adipocyte-derived endocrine factors, we recently found an adipocyte-specific secretory protein, adiponectin, which was decreased in obesity. Although obesity is associated with increased cardiovascular mortality and morbidity, the molecular basis for the link between obesity and vascular disease has not been fully clarified. The present study investigated whether adiponectin could modulate endothelial function and relate to coronary disease.Methods and ResultsFor the in vitro study, human aortic endothelial cells (HAECs) were preincubated for 18 hours with the indicated amount of adiponectin, then exposed to tumor necrosis factor-α (TNF-α) (10 U/mL) or vehicle for the times indicated. The adhesion of human monocytic cell line THP-1 cells to HAECs was determined by adhesion assay. The surface expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intracellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA. Physiological concentrations of adiponectin dose-dependently inhibited TNF-α-induced THP-1 adhesion and expression of VCAM-1, E-selectin, and ICAM-1 on HAECs. For the in vivo study, the concentrations of adiponectin in human plasma were determined by a sandwich ELISA system that we recently developed. Plasma adiponectin concentrations were significantly lower in patients with coronary artery disease than those in age- and body mass index-adjusted control subjects.ConclusionsThese observations suggest that adiponectin modulates endothelial inflammatory response and that the measurement of plasma adiponectin levels may be helpful in assessment of CAD risk.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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Optimizing the Percutaneous Interventional Outcomes for Patients With Diabetes MellitusResults of the EPISTENT (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial) Diabetic Substudy |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2477-2484
Steven Marso,
A. Lincoff,
Stephen Ellis,
Deepak Bhatt,
Jean-Francois Tanguay,
Neal Kleiman,
Talal Hammoud,
Joan Booth,
Shelly Sapp,
Eric Topol,
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摘要:
BackgroundStenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics.Methods and ResultsWe analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty-abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients (P=0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty-abciximab, and 6.2% for the stent-abciximab group (P=0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab (P=0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm;P=0.011) and a decrease in the late loss index (0.40 versus 0.60 mm;P=0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1.2% for stent-abciximab patients (P=0.11).ConclusionsThe combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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Heparin Blunts Endotoxin-Induced Coagulation Activation |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2485-2490
T. Pernerstorfer,
U. Hollenstein,
J.-B. Hansen,
M. Knechtelsdorfer,
P. Stohlawetz,
W. Graninger,
H.-G. Eichler,
W. Speiser,
B. Jilma,
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摘要:
BackgroundLipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation.Methods and ResultsIn a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F1+2(P<0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP;P<0.01); TF-positive monocytes doubled in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F1+2and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (P<0.01). Concomitantly, factor VIIa levels dropped by >50% at 50 minutes after initiation of either heparin infusion (P<0.01).ConclusionsThis experimental model proved the anticoagulatory potency of UFH and LMWH in the initial phase of experimental LPS-induced coagulation. Successful inhibition of thrombin generation also translates into blunted activation of coagulation factors upstream and downstream of thrombin.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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7. |
Abnormal Coronary Flow Velocity Reserve After Coronary Artery Stenting in PatientsRole of Relative Coronary Reserve to Assess Potential Mechanisms |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2491-2498
Morton Kern,
Sanjeev Puri,
Richard Bach,
Thomas Donohue,
Patrick Dupouy,
Eugene Caracciolo,
W. Craig,
Frank Aguirre,
Eduardo Aptecar,
Thomas Wolford,
Carol Mechem,
Jean-Luc Dubois-Rande,
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摘要:
BackgroundAbsolute coronary flow velocity reserve (CVR) after stenting may remain abnormal as a result of several different mechanisms. Relative CVR (rCVR=CVRtarget/CVRreference) theoretically normalizes for global microcirculatory disturbances and facilitates interpretation of abnormal CVR.Methods and ResultsTo characterize potential mechanisms of poststent physiology, CVR was measured using a Doppler-tipped angioplasty guidewire in 55 patients before and after angioplasty, after stenting, and in an angiographically normal reference vessel. For the group, the percent diameter stenosis decreased from 75±13% to 40±18% after angioplasty and to 10±9% (allP<0.05) after stent placement. After angioplasty, CVR increased from 1.63±0.71 to 1.89±0.55 (P<0.05) and after stent placement, to 2.48±0.75 (P<0.05 versus pre- and postangioplasty). After angioplasty, rCVR increased from 0.64±0.26 to 0.75±0.23 and after stent placement to 1.00±0.34. In 17 patients with CVRstent≤2.0, increased basal coronary flow, rather than attenuated hyperemia, was responsible in large part for the lower CVRstentcompared with patients having CVRstent>2.0. In 8 patients with CVRstent<2.0, a normal rCVR supported global microvascular disease. The subgroup of 9 patients with CVRstent<2.0 and abnormal rCVR (16% of the studied patients) may require a pressure-derived fractional flow reserve to differentiate persistent obstruction from diffuse atherosclerotic disease or microvascular stunning.ConclusionsAlthough a majority of patients after stenting normalize CVR for the individual circulation (ie, normal CVR or normal rCVR), in those with impaired CVRstent, the analysis of coronary flow dynamics suggests several different physiological mechanisms. Additional assessment may be required to fully characterize the physiological result for such patients to exclude remediable luminal abnormalities.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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Pharmacology and Biological Efficacy of a Recombinant, Humanized, Single-Chain Antibody C5 Complement Inhibitor in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2499-2506
Jane Fitch,
Scott Rollins,
Louis Matis,
Bernadette Alford,
Sary Aranki,
Charles Collard,
Michael Dewar,
John Elefteriades,
Roberta Hines,
Gary Kopf,
Philip Kraker,
Lan Li,
Ruth O'Hara,
Christine Rinder,
Henry Rinder,
Richard Shaw,
Brian Smith,
Gregory Stahl,
Stanton Shernan,
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摘要:
BackgroundCardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB.Methods and ResultsA humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (P<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase-MB release,P=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0.05) in patients who received 1 or 2 mg/kg.ConclusionsA single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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Cavotricuspid Isthmus Mapping to Assess Bidirectional Block During Common Atrial Flutter Radiofrequency Ablation |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2507-2513
Jian Chen,
Christian de Chillou,
Tarek Basiouny,
Nicolas Sadoul,
Jorge Da Silva Filho,
Isabelle Magnin-Poull,
Marc Messier,
Etienne Aliot,
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摘要:
BackgroundWe sought to compare published methods to an alternative approach ascertaining cavotricuspid isthmus (CTI) block during atrial flutter ablation.Methods and ResultsIn 39 consecutive patients who underwent an atrial flutter ablation procedure, a 24-pole mapping catheter was positioned so that 2 adjacent dipoles were bracketing the targeted CTI line of block (LOB), with proximal dipoles lateral to the LOB and distal dipoles in the coronary sinus. Two pacing sites were lateral (positions A and B) and 2 were septal (positions C and D) to the LOB, with locations A and D closest to the LOB. A resulting CTI block was accepted when 3 criteria were fulfilled: (1) complete reversal of the right atrial depolarization on the 24-pole catheter when pacing in the coronary sinus, (2) conduction delays from A to D greater than from B to D, and (3) conduction delays from D to A greater than from C to A. A successful CTI block was obtained in all patients. Before CTI block was obtained, a progressive CTI conduction delay was observed in 11 patients (28.2%). During the procedure, the 3 criteria defined above were either all present or all absent.ConclusionsThis study establishes that reversal of the atrial depolarization sequence up to the LOB is a definitive and mandatory criteria of successful atrial flutter ablation.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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10. |
Interactive Effect of Heart Rate and Muscle Sympathetic Nerve Activity on Blood Pressure |
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Circulation,
Volume 100,
Issue 25,
1999,
Page 2514-2518
Krzysztof Narkiewicz,
Virend Somers,
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摘要:
BackgroundSympathetic traffic to the peripheral vasculature and sympathetic discharge to the heart have complementary effects on blood pressure. Although faster heart rates have been linked to higher blood pressures, the relationship between muscle sympathetic nerve activity (MSNA) and long-term regulation of blood pressure is not clear. We tested the hypothesis that MSNA and heart rate are linked to blood pressure levels in normotensive subjects.Methods and ResultsWe studied normal young male (n=120) and female (n=48) subjects subdivided according to tertiles of heart rate and MSNA distributions. Systolic, diastolic, and pulse pressures were significantly different across the heart rate tertiles in male subjects, with the highest blood pressure values in the upper tertile of heart rate. No significant differences in blood pressure across the tertiles of MSNA were found. The relationship between MSNA and blood pressure, however, was affected by heart rate. MSNA did not influence blood pressure in the first and second heart rate tertiles. However, within the upper heart rate tertile, subjects with higher levels of MSNA had significantly higher systolic (P=0.02) and pulse (P=0.004) pressures than subjects with lower levels of MSNA. In female subjects, blood pressure was not different across the tertiles of heart rate or MSNA.ConclusionsMSNA and heart rate have interactive effects on systolic blood pressure and pulse pressure in normotensive male but not female subjects. No relationship between MSNA and blood pressure or pulse pressure is evident in subjects with slower heart rate. In male subjects with faster heart rates, higher levels of MSNA are associated with higher systolic and pulse pressures.
ISSN:0009-7322
出版商:OVID
年代:1999
数据来源: OVID
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