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1. |
The NHLBI Planning ProcessA Streamlined Approach |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1921-1921
Claude Lenfant,
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ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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2. |
Adenovirus-Mediated Gene Transfer of Soluble Vascular Cell Adhesion Molecule to Porcine Interposition Vein Grafts |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1922-1928
Shu-Jen Chen,
James M. Wilson,
David W.M. Muller,
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摘要:
Background The efficacy of aorto-coronary vein grafting is limited by early graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus-mediated transfer of genes encoding inhibitory proteins may prevent or slow progression of vein graft disease.Methods and Results Recombinant adenoviruses containing the cDNA for the marker gene lacZ (Ad.CMVlacZ) or soluble vascular cell adhesion molecule (sVCAM) (Ad.CBsVCAM) were used to infect segments of porcine jugular vein or human saphenous vein. Ex vivo testing showed expression of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24 hours, with an increase in transfection efficiency with increasing incubation time. Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization.Conclusions We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. The potential for this approach to prevent early vein graft thrombosis or accelerated vein graft atherosclerosis requires further evaluation. (Circulation. 1994;89:1922-1928.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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3. |
Biodegradable Microspheres Containing a Colchicine Analogue Inhibit DNA Synthesis in Vascular Smooth Muscle Cells |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1929-1933
K.L. March,
S. Mohanraj,
P.P.K. Ho,
R.L. Wilensky,
D.R. Hathaway,
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摘要:
Background Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury.Local application of agents capable of modulating vascular responses, including smooth muscle cell proliferation, has been achieved, but difficulty in maintaining active levels locally has been a factor limiting the efficacy of such approaches. One strategy to maintain adequate levels is the local delivery of microspheres that release active agents over sustained time periods.Methods and Results We incorporated a colchicine analogue into biodegradable microspheres composed of a lactic acid/glycolic acid copolymer and characterized their drug release behavior as well as their effects on bovine aortic smooth muscle cells (BASMCs) in culture.Drug release was evaluated by spectrophotometric assay. Drug effects on DNA synthesis were measured by thymidine incorporation after addition of serum to subconfluent cells synchronized by serum withdrawal as well as in asynchronous cell populations. Polymeric microspheres incorporating 10% to 17% drug by weight and averaging 6 microns in size were found to release the colchicine analog in buffered saline solutions over more than several weeks. Drug-loaded particles inhibited DNA synthesis completely, with EC50values ranging from 0.001 to 0.005 g% (wt/wt). Morphological changes suggesting microtubule depolymerization were observed after drug particle treatment, with similar EC50values. Microspheres allowed to contact the cell surface demonstrated effects similar to those seen with microspheres suspended in the nutrient medium by porous polycarbonate filters, at EC50values approximately fivefold lower. In contrast, control microspheres composed only of polymer with no incorporated active drug demonstrated no observable toxicity to BASMCs and <40% inhibition of thymidine incorporation even in suspensions containing up to 0.5 g% particles.Conclusions Biodegradable microspheres were fashioned that release a colchicine analogue and inhibit DNA synthesis in smooth muscle cells.Drug-loaded polymeric particles are candidates for local delivery at sites of arterial injury to decrease restenosis. (Circulation. 1994;89:1929-1933.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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4. |
Cellular and Molecular CardiologyN-Terminal Proatrial Natriuretic FactorAn Independent Predictor of Long-Term Prognosis After Myocardial Infarction |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1934-1942
Christian Hall,
Jean L. Rouleau,
Lemuel Moye,
Jacques de Champlain,
Daniel Bichet,
Marc Klein,
Bruce Sussex,
Milton Packer,
Jacques Rouleau,
Malcolm O. Arnold,
Gervasio A. Lamas,
Francois Sestier,
Stephen S. Gottlieb,
Chuan-Chuan C. Wun,
Marc A. Pfeffer,
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摘要:
Background Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure.Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly.Methods and Results To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF.Conclusions The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure. (Circulation. 1994;89:1934-1942.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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5. |
Cellular and Molecular CardiologyHuman Vascular Smooth Muscle Cells Contain Functional Estrogen Receptor |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1943-1950
Richard H. Karas,
Bruce L. Patterson,
Michael E. Mendelsohn,
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摘要:
Background The decreased incidence of coronary artery disease observed in postmenopausal women given estrogen (E2) replacement demonstrates an atheroprotective effect of E2 that is generally believed to be mediated by indirect, E2-induced changes in cardiovascular risk factor profiles. We hypothesized that the atheroprotective effect of E2 may be in part mediated by a direct effect of E2 on vascular smooth muscle cells (VSMCs). Therefore, a series of experiments was performed to determine whether human VSMCs contain a competent E2 receptor, a ligand-activated transcription factor known to mediate E2-induced effects in nonvascular cells.Methods and Results Ribonuclease protection assays, with a probe derived from the human E2 receptor, were used to demonstrate E2-receptor mRNA in human saphenous vein VSMCs. To show that VSMCs contain E2-receptor protein as well as message, immunoblotting and immunofluorescence studies with a monoclonal anti-E2-receptor antibody were performed, and E2-receptor protein was detected by both methods. Transient transfection assays using a specific E2-responsive reporter system were used next to determine whether the VSMC E2 receptor is capable of E2-induced transcriptional transactivation. Initial studies using mammary artery-derived VSMCs resulted in a 2.4-fold increase in reporter activity in response to 10-7mol/L E2. Subsequent studies using saphenous vein VSMCs demonstrated increasing levels of reporter activation as the concentration of E2 was increased from 10-9mol/L (1.3-fold increase; SEM, 0.07; P=.05, n=3) to 10-7mol/L (1.6-fold increase; SEM, 0.04; P=.002, n=6). The specificity of the E2-induced transactivation of the reporter gene was shown by dose-dependent inhibition of transactivation by the pure E2 antagonist ICI 164,384 and by enhancement of the transactivation by simultaneous overexpression of the E2 receptor.Conclusions We have demonstrated for the first time that human VSMCs express E2-receptor mRNA and protein and that the E2 receptor in VSMCs is capable of estrogen-dependent gene activation. These data suggest a mechanism by which estrogen may directly alter VSMC function. (Circulation. 1994;89:1943-1950.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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6. |
Coronary Heart Disease/Myocardial InfarctionNorepinephrine-Induced Human Platelet Activation in Vivo Is Only Partly Counteracted by Aspirin |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1951-1957
N.H. Wallen,
P. Hjemdahl,
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摘要:
Background Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation.Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment.Methods and Results Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta -thromboglobulin (beta -TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P<.001). Platelet secretion (beta -TG levels) increased during high-dose infusion (P<.01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B (2) by 62+-5% (P<.001) and attenuated platelet aggregability at rest (P<.05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta -TG levels and the urinary excretion of high-molecular-weight beta -TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta -TG was abolished.Conclusions Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans.Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans. (Circulation. 1994;89:1951-1957.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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7. |
Coronary Heart Disease/Myocardial InfarctionIs 'silent' Myocardial Ischemia Really as Severe as Symptomatic Ischemia?The Analytical Effect of Patient Selection Biases |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1958-1966
Jacob Klein,
Susan Y. Chao,
Daniel S. Berman,
Alan. Rozanski,
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摘要:
Background The clinical significance of exercise-induced chest pain remains controversial, as reflected by sharply discordant clinical results within the medical literature. Thus, we developed a prospective study to compare the functional significance of silent versus symptomatic ischemia and to evaluate whether patient selection biases influence this analysis.Methods and Results We evaluated 117 patients (mean age, 63+-9 years) with ischemic ST-segment depression during treadmill testing. Each patient underwent Tl-201 myocardial perfusion single-photon emission computed tomography (SPECT) after exercise followed by 24-ambulatory ECG monitoring. Patients were divided into silent versus symptomatic cohorts and were compared for the degree of hemodynamic, exercise and ambulatory ECG, and thallium abnormalities during stress testing. Analyses were repeated as the patient population became increasingly restricted. Compared with the silent patients, patients with chest pain during exercise had a shorter exercise duration (P<.009), lower peak heart rate (P=.009) and double product (P=.005), lower heart rate threshold for ST depression (P<.05), more episodes of ambulatory ST-segment depression (P<.05), a higher frequency of ischemia abnormalities during Tl-201 SPECT (P=.02), and higher summed Tl reversibility scores (P=.002). As the population became increasingly restricted, the relative magnitude of differences in silent versus symptomatic cohorts diminished, whereas the absolute magnitude of ischemic abnormalities progressively increased in both cohorts. For example, within the restricted group having ischemia on both exercise and ambulatory ECG, 50% of the silent cohort had severe ischemia on Tl SPECT (five or more reversible defects) and more than one third demonstrated the ominous finding of transient left ventricular dilation after exercise.Conclusions The induction of chest pain is associated with substantially more functional abnormalities when it is analyzed in a relatively "broad-spectrum" coronary artery disease population; by contrast, chest pain tends to lose its apparent value as a clinical test parameter when its analysis is restricted to coronary artery disease populations with a greater a priori likelihood of manifesting inducible ischemia. These findings may help resolve some of the previous discordant literature reports. (Circulation. 1994;89:1958-1966.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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8. |
Coronary Heart Disease/Myocardial InfarctionPlasma Apolipoprotein Concentrations in Young Adults With a Parental History of Premature Coronary Heart Disease and in Control SubjectsThe EARS Study |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1967-1973
M. Rosseneu,
J.C. Fruchart,
J.M. Bard,
V. Nicaud,
N. Vinaimont,
F. Cambien,
G. De Backer,
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摘要:
The European Atherosclerosis Research Study (EARS) is a multicenter collaborative project within the European community. Its main objective is to study in young individuals the biological expression of a paternal history of premature coronary heart disease and to analyze the relative contribution of genetic and environmental factors to this expression. This study was carried out in 14 centers in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched control subjects. Plasma apolipoproteins A-I, B, A-II, A-IV, and E and lipoprotein (Lp) A-I lipoparticles were measured in this student population. Comparison of the values between cases and control subjects showed significantly higher apo B levels in cases compared with control subjects, and these differences were homogeneous throughout Europe. Regional differences were observed for apo E levels with an increasing north-south gradient, which was inversely related to that observed for triglycerides. A stepwise regression analysis including the lipid and apolipoprotein variables showed that apo B and triglycerides were the strongest discriminators between offspring of fathers with premature coronary heart disease and control subjects. (Circulation. 1994;89:1967-1973.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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9. |
Coronary Heart Disease/Myocardial InfarctionDeterminants of Severity of Coronary Artery Disease in Australian Men and Women |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1974-1981
X.L. Wang,
C. Tam,
R.M. McCredie,
D.E.L. Wilcken,
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摘要:
Background Factors predicting the occurrence of premature coronary artery disease (CAD) may not be quantitatively the same as those predicting CAD severity, particularly in women, in whom there have been few studies.50%) luminal obstructions and from a coronary disease severity score. We related severity to quantitative and categorical atherogenic variables and assessed severity of angina (no angina, stable angina, or unstable angina) at the time of study in the same way. There were eight variables independently predictive of severity: in descending order of relative importance, male gender, diabetes, smoking dose, ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C), lipoprotein(a) (Lp(a)), age, positive family history, and hypertension. These correctly classified 43.3% of patients into no-, one-, two-, and three-vessel disease categories and accounted for 25.8% of variance of severity. Among 246 patients not taking lipid-lowering or beta -blocking drugs, these variables (in slightly different order) correctly classified 49.2% of patients and accounted for 36% of the variance. Among men (n=427), seven significant variables correctly classified 39.3% of patients compared with 54.5% in women (n=167). For those not taking the above drugs, these proportions were 49.4% and 65.4%, respectively. Among the quantitative variables, total smoking dose was the most predictive independent variable irrespective of current or ex-smoking habit and was more predictive in women than in men; of the lipid variables, high TC/HDL-C (or low HDL-C) and high Lp(a) were consistently highly predictive for all patients and in the subgroup analyses. Patients with unstable angina had higher coronary severity scores and Lp(a) levels and were more likely to have diabetes, hypertension, or a positive family history.Conclusions We conclude that the quantitative variables most relevant to severity of premature CAD and to its prevention in Australian men and women are total amount of lifetime smoking, TC/HDL-C (or HDL-C), and Lp(a) and that patients with unstable versus stable angina usually have more severe disease and higher Lp(a). (Circulation. 1994;89: 1974-1981.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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10. |
Coronary Heart Disease/Myocardial InfarctionRecombinant Human Superoxide Dismutase (h-SOD) Fails to Improve Recovery of Ventricular Function in Patients Undergoing Coronary Angioplasty for Acute Myocardial Infarction |
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Circulation,
Volume 89,
Issue 5,
1994,
Page 1982-1991
John T. Flaherty,
Bertram Pitt,
John W. Gruber,
Richard R. Heuser,
Donald A. Rothbaum,
Lawrence R. Burwell,
Barry S. George,
Dean J. Kereiakes,
David Deitchman,
Nancy Gustafson,
Jeffrey A. Brinker,
Lewis C. Becker,
G.B. John Mancini,
Eric Topol,
Steven W. Werns,
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摘要:
Background Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction.Methods and Results One hundred twenty patients were randomized to receive placebo (n=59) or h-SOD (n=61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg x kg-1x min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD.Conclusions The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction. (Circulation. 1994;89:1982-1991.)
ISSN:0009-7322
出版商:OVID
年代:1994
数据来源: OVID
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