bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction.
Authors: Hall C , Rouleau J L , Moyè L , de Champlain J , Bichet D , Klein M , Sussex B , Packer M , Rouleau J , Arnold M O 
Published: June 2012

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.
Human vascular smooth muscle cells contain functional estrogen receptor.
Authors: Karas R H , Patterson B L , Mendelsohn M E 
Published: June 2012

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(-7) mol/L E2. Subsequent studies using saphenous vein VSMCs demonstrated increasing levels of reporter activation as the concentration of E2 was increased from 10(-9) mol/L (1.3-fold increase; SEM, 0.07; P = .05, n = 3) to 10(-7) mol/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.
Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin.
Authors: Larsson P T , Wallén N H , Hjemdahl P 
Published: June 2012

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 B2 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.
Determinants of severity of coronary artery disease in Australian men and women.
Authors: Wang X L , Tam C , McCredie R M , Wilcken D E 
Published: June 2012

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.

METHODS AND RESULTS
To determine factors predictive of severity of CAD and of angina pectoris, we documented atherogenic variables and the extent of CAD at angiography in 594 consecutively studied men and women aged 65 years or less. Severity was assessed from the number of involved major coronary arteries with significant (> 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).
Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power. Validation and noninvasive application.
Authors: Sharir T , Feldman M D , Haber H , Feldman A M , Marmor A , Becker L C , Kass D A 
Published: June 2012

BACKGROUND
Noninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment.

METHODS AND RESULTS
To validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was minimally influenced by afterload. However, PWRmx/EDV2 was not significantly altered by either loading change. PWRmx/EDV2 did vary with contractility, correlating closely with changes in the end-systolic pressure-volume relation (r = .91, P < .001). To test the noninvasive application of this index, 12 additional patients were studied, with PWRmx/EDV2 derived from nuclear ventriculography combined with a novel method to measure central arterial pressures. Subjects received intravenous nitroprusside or dobutamine in random order. Ejection fraction increased similarly with both agents (+42.9 +/- 8.9% for dobutamine and +29.4 +/- 5.3% for nitroprusside, both P < .01). In contrast, PWRmx/EDV2 did not significantly change with nitroprusside but increased by 126 +/- 16.1% with dobutamine (P < .01).

CONCLUSIONS
Preload-adjusted PWRmx is a steady-state index of ventricular systolic function that is sensitive to inotropic state and minimally influenced by physiological changes in afterload impedance or volume load. It appears useful for noninvasive cardiac-specific analysis of acute drug effects.
Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion.
Authors: Paulus W J , Vantrimpont P J , Shah A M 
Published: June 2012

BACKGROUND
In isolated mammalian cardiomyocytes, papillary muscle preparations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-elevating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. In the present study, the effect of NO on left ventricular (LV) relaxation and diastolic distensibility was investigated in humans.

METHODS AND RESULTS
The NO donor substance sodium nitroprusside was infused during cardiac catheterization in the global coronary bed of the LV of patients (n = 13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease. Sodium nitroprusside was infused intracoronarily at a dosage (< or = 4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary infusion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During global intracoronary nitroprusside infusion, there was a decrease in heart rate from 78 +/- 11 to 76 +/- 12 beats per minute (P < .05), in LV peak systolic pressure from 161 +/- 18 to 146 +/- 18 mm Hg (P < .001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dtmin) from 432 +/- 36 to 419 +/- 36 milliseconds (P < .01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diastolic volume increased from 158 +/- 34 to 165 +/- 40 mL (P < .05), whereas LV end-diastolic pressure fell from 18 +/- 5 to 12 +/- 3 mm Hg (P < .02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressure-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n = 2) or after the global intracoronary infusion. The decrease in LV peak systolic pressure observed during right atrial infusion was significantly smaller (P < .01) than during global intracoronary infusion.

CONCLUSIONS
The present study reveals reduced LV pressure development, an LV relaxation-hastening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside. These effects appeared to be unrelated to systemic vasodilation or to pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to increase cyclic GMP or through modification of other cellular proteins.
Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine.
Authors: Tsao P S , McEvoy L M , Drexler H , Butcher E C , Cooke J P 
Published: June 2012

BACKGROUND
We have shown that chronic administration of the nitric oxide (NO) precursor L-arginine normalizes NO-dependent vasodilation and markedly inhibits atherogenesis in a hypercholesterolemic rabbit model. We hypothesized that this antiatherogenic effect is due to modulation of endothelial adhesiveness by endothelium-derived NO.

METHODS AND RESULTS
New Zealand White rabbits were fed normal chow (Cont), a high-cholesterol diet (Chol), a high-cholesterol diet supplemented with L-arginine (Arg), or a normal diet supplemented with the NO synthase antagonist L-nitroarginine (L-NA) for 2 weeks. In additional studies, some animals receiving L-NA were also treated with hydralazine to normalize blood pressure. After 2 weeks, thoracic aortas were harvested, opened longitudinally, and placed in a culture dish with the endothelial surface exposed to medium containing WEHI 78/24 cells, a monocytoid cell line. After incubation with the monocytoid cells for 30 minutes on a rocking platform, the aortic segments were washed repeatedly to remove nonadherent cells and adherent cells counted by epifluorescent microscopy. Monocytoid cell binding to aortic endothelium was significantly increased in Chol (P < .001 versus Cont); binding was markedly reduced in arginine-fed hypercholesterolemic animals (P < .05, Arg versus Chol). Monocytoid cell binding to aortic endothelium was also significantly increased in L-NA (P < .05); hydralazine normalized blood pressure but did not reduce monocytoid cell binding. To confirm that alterations in NO activity modulate endothelial cell-monocyte interaction, the release of nitrogen oxides (NOx) by thoracic aortas was assessed by a chemiluminescent technique. The concentration of NOx in the conditioned medium from segments of Arg thoracic aortas was significantly greater than that from Cont aortas, whereas that from L-NA aortas was significantly less.

CONCLUSIONS
Hypercholesterolemia enhances the adhesiveness of aortic endothelium for monocytes; this effect is attenuated by dietary L-arginine. Conversely, inhibition of NO synthesis enhances monocyte binding. The results suggest that endothelium-derived NO plays an important role in regulating the endothelial adhesiveness for monocytes. Alterations in NO activity may play a critical role in atherogenesis.
Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.
Authors: Schieffer B , Wirger A , Meybrunn M , Seitz S , Holtz J , Riede U N , Drexler H 
Published: June 2012

BACKGROUND
After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure.

METHODS AND RESULTS
Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo).

CONCLUSIONS
The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction.
Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.
Authors: Jugdutt B I , Khan M I 
Published: June 2012

BACKGROUND
Prolonged nitrate therapy during healing between 2 days and 6 weeks after anterior myocardial infarction has the potential for limiting further left ventricular remodeling (or changes in topography) and preserving function. Longterm therapy throughout healing over 6 weeks might be more beneficial than short-term therapy over the first 2 weeks after infarction.

METHODS AND RESULTS
The effect of prolonged nitrate therapy between 2 days and 6 weeks during healing after infarction on serial parameters of ventricular remodeling (scar expansion, scar thinning, ventricular dilation, and hypertrophy) and function (asynergy or akinesis plus dyskinesis and ejection fraction) by serial two-dimensional echocardiography, hemodynamics, postmortem topography (computerized planimetry, geometric maps, and radiographs), and collagen content (hydroxyproline) was studied in 64 instrumented dogs randomized 2 days after left anterior descending coronary artery ligation to various nitrate regimens (n = 32) over the first 2 weeks (subgroup 1: 2% transdermal nitroglycerin at 8 AM and 4 PM, n = 6; subgroup 2: 2% transdermal nitroglycerin plus 2.6 mg of sustained-release oral nitroglycerin at 8 AM, 3 PM, and 10 PM, n = 5; subgroup 3: oral isosorbide dinitrate, 30 mg at 8 AM and 4 PM, n = 11) or 6 weeks (subgroup 4: isosorbide dinitrate, n = 10) and in matching controls (n = 32). Nitrate therapy reduced left atrial pressure, mean arterial pressure, and the rate-pressure product compared with controls over the 6 weeks. Postmortem scar mass and hydroxyproline were similar in control and nitrate groups. However, scar stretching and thinning, cavity dilation, noninfarct wall hypertrophy, and apical bulging were less with nitrates, especially in the long-term subgroup 4. In vivo remodeling parameters between 2 days and 6 weeks after ligation showed that, compared with controls, nitrate therapy prevented further stretching of the asynergic segment, decreased the expansion index, decreased further scar thinning, prevented the increase in ventricular volumes, reduced the frequency of ventricular aneurysm, prevented the increase in ventricular mass, reduced the extent of asynergy, and improved ejection fraction. Although the beneficial effect on topography and function was seen in all nitrate subgroups, the overall benefit was greater with long-term therapy over 6 weeks (subgroup 4) than short-term therapy confined to the first 2 weeks (subgroups 1, 2, and 3).

CONCLUSIONS
Prolonged nitrate therapy, in various regimens during healing after infarction, effectively reduced left ventricular loading and prevented infarct thinning, further infarct expansion, progressive ventricular dilation, and the increase in mass. These effects were associated with decreased asynergy and improved ejection fraction. The beneficial effects were greater with long-term therapy over 6 weeks than short-term therapy over the first 2 weeks.