bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study on the proarrhythmic effects of some antiarrhythmic agents.
Authors: Dhein S , Müller A , Gerwin R , Klaus W 
Published: June 2012

BACKGROUND
A main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available.

METHODS AND RESULTS
To analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation ("breakthrough points" [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heartbeats (under treatment) compared with control was evaluated by determination of the percentage of identical BTPs (deviation < or = 1 mm) and of similar VECs (deviation < or = 5 degrees). BTP and VEC were reduced by all antiarrhythmic agents tested (propafenone = flecainide > quinidine > ajmaline > procainamide > disopyramide > mexiletine = lidocaine > sotalol), indicating a more or less pronounced disturbance of the epicardial activation process. Treatment with propafenone, quinidine, and disopyramide and to a lesser extent sotalol prolonged the activation-recovery interval (ARI). ARI dispersion was greatly enhanced by flecainide and was reduced by sotalol. In addition, it could be shown that propranolol is able to reduce the proarrhythmic action of flecainide. This effect seemed to be due to a reduction of the flecainide-induced increase in ARI dispersion.

CONCLUSIONS
From the results of our study, we propose the following rank order of the arrhythmogenic risk: flecainide > propafenone > quinidine > ajmaline > disopyramide > procainamide > mexiletine, lidocaine > sotalol. Moreover, we conclude that propranolol given additionally may be helpful in reducing the proarrhythmic risk of flecainide.
Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study.
Authors: Manolio T A , Ettinger W H , Tracy R P , Kuller L H , Borhani N O , Lynch J C , Fried L P 
Published: June 2012

BACKGROUND
Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths.

METHODS AND RESULTS
This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes.

CONCLUSIONS
Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies.
Hemodynamic characteristics of the early phase of primary hypertension. The Dutch Hypertension and Offspring Study.
Authors: van Hooft I M , Grobbee D E , Waal-Manning H J , Hofman A 
Published: June 2012

BACKGROUND
The hemodynamic characteristics of the early phase of primary hypertension are subject to debate. In particular, it remains unclear whether an increased vascular peripheral resistance or a raised cardiac output is involved as the primary hemodynamic alteration in hypertension.

METHODS AND RESULTS
We studied hemodynamic characteristics and oxygen consumption in relation to 24-hour ambulatory blood pressure measurements in three groups of normotensive children with a different familial predisposition for hypertension. Selection of participants was based on parental blood pressure levels. Mean 24-hour blood pressure was higher in the offspring of two hypertensive parents compared with the offspring of two normotensive parents; there was a difference of 4.7 mm Hg (95% confidence interval [CI], 1.8-7.6) for systolic blood pressure and a difference of 4.8 mm Hg (CI, 2.3-7.3) for diastolic blood pressure. The 24-hour blood pressure pattern was consistently at a higher level for both systolic and diastolic blood pressures in the offspring of two hypertensive parents compared with the offspring of two normotensive parents. The smallest differences in blood pressure were seen at night, and the largest differences in blood pressure between the groups of offspring were seen during periods of physical activity. Echocardiographic examination combined with registration of oxygen consumption did not show a difference in cardiac index and arteriovenous oxygen difference between the study groups. However, differences in cardiac dimensions were apparent, with an increased left ventricular mass index (8.7 g/m2; CI, 2.4-15.0) in the offspring of two hypertensive parents.

CONCLUSIONS
These findings do not support the existence of a hyperkinetic circulatory phase but may indicate the presence of an increased left ventricular mass in early primary hypertension.
Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. The Atherosclerosis Risk in Communities Study.
Authors: Malinow M R , Nieto F J , Szklo M , Chambless L E , Bond G 
Published: June 2012

BACKGROUND
Plasma levels of homocyst(e)ine are elevated in certain patients with occlusive arterial diseases. We extended these findings to asymptomatic adults.

METHODS AND RESULTS
We determined plasma homocyst(e)ine levels in 287 pairs of asymptomatic adults. Cases and controls were defined on the basis of intimal-medial thickness of the carotid wall as measured by B-mode ultrasound. Study subjects had no history of atherosclerotic disease and were selected from a probability sample of 15,800 men and women between 45 and 64 years old. Subjects with thickened intimal-medial carotid walls (cases) had higher plasma homocyst(e)ine levels than controls (p < 0.001). The odds ratio for having a thickened carotid artery wall was 3.15 (p < 0.001) for subjects in the top quintile of plasma homocyst(e)ine levels (> 10.5 mumol/L) compared with those in the bottom quintile (< 5.88 mumol/L).

CONCLUSIONS
The present study as well as observations on the common occurrence of elevated plasma homocyst(e)ine levels in patients with occlusive arterial diseases suggest that clinical trials should be conducted to determine whether normalization of hyperhomocyst(e)inemia may prevent progression of atherosclerosis.
Lesion-to-lesion independence of restenosis after treatment by conventional angioplasty, stenting, or directional atherectomy. Validation of lesion-based restenosis analysis.
Authors: Gibson C M , Kuntz R E , Nobuyoshi M , Rosner B , Baim D S 
Published: June 2012

BACKGROUND
Since many restenosis trials include patients in whom more than one lesion is treated, analysis of the angiographic data on a "per lesion" basis might be confounded by potential correlations of restenosis among multiple treated lesions within each patient. The goals of this study were: 1) to determine whether there was any correlation in the rate of restenosis among multiple lesions that underwent conventional angioplasty, stenting, or directional atherectomy within the same patient and 2) to determine whether lesions treated in a multilesion intervention experience a different magnitude of restenosis than lesions undergoing single-lesion procedures.

METHODS AND RESULTS
Of 441 patients treated by Palmaz-Schatz stenting (n = 114), directional atherectomy (n = 100), or conventional balloon angioplasty (n = 227), 67 underwent multilesion procedures involving treatment of 146 lesions. A general linear model with intraclass correlation (GLIMIC) was used to calculate the coefficient of correlation (rho) of the change in the measured minimum luminal diameter (late loss) from the time of the initial procedure to 6-month angiogram among the multiple lesions within the same patient for all 441 patients. This showed no correlation among multiple lesions within the same patient for the late loss in minimum luminal diameter (rho = -0.12 [95% CI: -0.40, 0.12]), among lesions in the same vessel (rho = 0.14 [95% CI: -0.34, 0.62]), or among different vessels (rho = -0.18 [95% CI: -0.52, 0.16]), suggesting that the magnitude of late loss is independent among multiple lesions within the same patient. There was no difference (p = 0.96) between the observed incidence of zero-, one-, and two-vessel restenosis (> or = 50% diameter stenosis at follow-up) for patients with multiple-lesion treatment and that predicted assuming lesion-to-lesion independence. Similarly, there was no difference in late loss or in the overall binary restenosis rate when single-lesion procedures were compared with multilesion procedures. Multivariable analysis of the late loss in lumen diameter (which adjusted for the effects of the acute result and the device used) demonstrated no independent effect (p = 0.20) of single-lesion versus multilesion status.

CONCLUSIONS
Luminal encroachment appears to occur at independent rates among multiple lesions treated in a single patient. The observed incidence of restenosis for patients with multiple treated lesions is accurately predicted assuming independent probabilities of restenosis. Lesion-based analysis, even when including multiple treated lesions within the same patient, is thus valid for evaluating conventional angioplasty, stenting, or directional atherectomy.
Angiographic and hemodynamic determinants of myocardial ischemia during adenosine thallium-201 scintigraphy in coronary artery disease.
Authors: Nishimura S , Kimball K T , Mahmarian J J , Verani M S 
Published: June 2012

BACKGROUND
Myocardial ischemia attributed to coronary steal may occur in some patients receiving pharmacological coronary vasodilation. ECG ST-segment depression is a marker of myocardial ischemia in these patients, but the factors determining the presence or absence of ischemia are not well known.

METHODS AND RESULTS
To examine the angiographic, hemodynamic, and scintigraphic determinants of adenosine-induced ischemic ST-segment depression in patients with coronary artery disease, we studied 65 consecutive patients (45 men and 20 women; mean age, 65 +/- 12 years) who showed reversible perfusion defects during adenosine (140 micrograms.kg-1.min-1 for 6 minutes) 201Tl single-photon emission computed tomography. Patients with prior myocardial infarction were excluded. Ischemic ST depression occurred in one third of the whole cohort (22 of 65 patients). The presence of coronary collateral vessels (p = 0.001), systolic blood pressure at baseline (p = 0.006), and adenosine-induced anginal chest pain (p = 0.011) were the only significant independent predictors of ischemic ST-segment depression by stepwise logistic regression analysis. Rate-pressure product at baseline, systolic blood pressure, heart rate, rate-pressure product, increase in heart rate, and rate-pressure product during adenosine infusion and maximal percent stenosis were variables also significantly related to ischemic ST depression by univariate analysis but were not predictive after the three primary variables were included in the regression model. Perfusion defect size, number of diseased vessels, and age did not correlate with ST-segment depression.

CONCLUSIONS
The presence of collaterals, which may predispose to coronary collateral steal, is the most significant correlate of ischemic ST-segment depression during adenosine infusion. Systolic blood pressure at baseline, which may affect the myocardial oxygen supply/demand ratio and anginal chest pain induced by adenosine, are additional variables related to ischemic ST-segment depression during adenosine infusion.
Cyclosporine A has no direct effect on collagen metabolism by cardiac fibroblasts in vitro.
Authors: Eleftheriades E G , Ferguson A G , Samarel A M 
Published: June 2012

BACKGROUND
Cyclosporine A has been implicated in the pathogenesis of myocardial interstitial fibrosis observed in heart transplant recipients. However, other confounding variables such as posttransplantation hypertension and rejection episodes may also be responsible for interstitial fibrosis development and associated abnormalities in ventricular diastolic function. Therefore, we examined whether cyclosporine A directly or indirectly affects fibrillar collagen metabolism by cardiac fibroblasts in vitro.

METHODS AND RESULTS
Rat cardiac fibroblasts were isolated by collagenase digestion. Subconfluent cultures were then maintained (24 hours) in serum-containing or serum-free medium before addition of cyclosporine A (50-1,000 ng/mL). After an additional 24 hours, total procollagen synthesis, accumulation, and degradation were analyzed by measuring hydroxyproline content in the cell monolayer and in the ethanol-soluble and ethanol-precipitable fractions of the culture medium. mRNA levels for alpha 1(I) and alpha 1(III) procollagen polypeptides were assessed 2, 6, 12, and 24 hours after cyclosporine A treatment using Northern blot analysis. The results were compared with control cultures maintained in the absence of cyclosporine A. There were no differences in procollagen gene expression, total procollagen synthesis, accumulation, or degradation in cardiac fibroblasts treated directly with cyclosporine A, in concentrations up to 1,000 ng/mL, compared with untreated cells. In additional experiments, we examined whether cyclosporine A might stimulate the production of collagen regulatory substances by cardiac myocytes in culture. However, addition of conditioned media from neonatal myocytes maintained in the presence and absence of cyclosporine A (1,000 ng/mL) also had no effect on collagen deposition by cardiac fibroblasts.

CONCLUSIONS
We conclude that cyclosporine A has no direct effect on collagen metabolism by cultured cardiac fibroblasts in vitro. In addition, we have excluded a paracrine effect of ventricular myocytes on collagen production in the presence of cyclosporine A. These results suggest that factors other than cyclosporine A are responsible for the interstitial fibrosis observed in cardiac allografts.
Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty.
Authors: Topol E J , Bonan R , Jewitt D , Sigwart U , Kakkar V V , Rothman M , de Bono D , Ferguson J , Willerson J T , Strony J 
Published: June 2012

BACKGROUND
Since the inception of coronary angioplasty, heparin with or without aspirin has been routinely given intraprocedurally to avoid coronary thrombotic complications. Recently, the direct thrombin inhibitor hirulog has been demonstrated to inactivate clot-bound thrombin. The present study was a multicenter dose escalation of hirulog to determine its appropriate dose and feasibility as the sole anticoagulant during coronary angioplasty.

METHODS AND RESULTS
At 11 participating centers, 291 patients undergoing elective coronary angioplasty and pretreated with 325 mg aspirin daily were enrolled in sequential groups of intravenously administered hirulog instead of heparin as follows: group 1: bolus, 0.15 mg/kg; infusion, 0.6 mg.kg-1.hr-1 (54 patients); group 2: bolus, 0.25 mg/kg; infusion, 1.0 mg.kg-1.hr-1 (53 patients); group 3: bolus, 0.35 mg/kg; infusion, 1.4 mg.kg-1.hr-1 (44 patients); group 4: bolus, 0.45 mg/kg; infusion, 1.8 mg.kg-1.hr-1 (74 patients); and group 5: bolus, 0.55 mg/kg; infusion, 2.2 mg.kg-1.hr-1 (54 patients). The hirulog infusion was maintained for 4 hours; the primary end point was abrupt vessel closure within 24 hours of the initiation of the procedure. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) were serially monitored. Abrupt vessel closure occurred in 18 patients (6.2%). By intention to treat, the abrupt closure event rate for groups 1-3 was 11.3% compared with 3.9% in groups 4 and 5 (p = 0.052). There were no significant bleeding complications except for one patient in group 1, who received a two-unit transfusion. A dose-response curve of both ACTs and aPTTs was noted; no coronary thrombotic closures occurred in the small number of patients with ACT > 300 seconds.

CONCLUSIONS
The present study documents for the first time that it is possible to perform coronary angioplasty with an anticoagulant other than heparin in aspirin-pretreated patients. Hirulog was associated with a rapid onset, dose-dependent anticoagulant effect, minimal bleeding complications, and at doses of 1.8-2.2 mg/kg, a rate of 3.9% for abrupt vessel closure.
Dose-dependent effect of aspirin on carotid atherosclerosis.
Authors: Ranke C , Hecker H , Creutzig A , Alexander K 
Published: June 2012

BACKGROUND
Antiplatelet treatment with aspirin is well established as secondary prophylaxis after a transient ischemic attack or minor ischemic stroke, but the effect of aspirin treatment on the course of carotid atherosclerosis is unknown. We investigated the effect of aspirin on the initial stages of carotid atherosclerosis.

METHODS AND RESULTS
Patients were recruited from a prospective, randomized, double-blind clinical trial to compare two doses of aspirin (900 mg versus 50 mg daily) with regard to restenoses after lower limb angioplasty. Of the 383 patients admitted to the angioplasty trial, 27 patients with 104 small carotid atheroma (< 50% lumen narrowing) were examined at entry and after 1 year of aspirin treatment with the use of a high-resolution ultrasound duplex system. Disease progression and regression were defined by a change of maximal plaque area (as measured by longitudinal ultrasound sections) of more than 2 SDs of the method. The change in plaque area was significantly different for the treatment groups: Average plaque size remained unchanged after treatment with 900 mg aspirin daily but increased markedly after treatment with 50 mg aspirin daily (p = 0.011). There were significantly more lesions in the 50-mg group showing progression than in the 900-mg group (23 plaques [47%] versus 13 plaques [24%], p = 0.025). Ultrasonic disappearance of a lesion was observed only in the 900-mg group in nine cases (seven soft plaques and two ulcerative plaques, p = 0.018). The six patients on 50 mg aspirin who continued smoking during the study showed significantly more progression compared with the seven nonsmokers in the 50-mg group (17 plaques [59%] versus six plaques [30%], p = 0.038).

CONCLUSIONS
The results of our study indicate that aspirin treatment slows carotid plaque growth in a dose-dependent fashion, with a dose of 900 mg daily more efficient than 50 mg daily.
Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study.
Authors: Lowe G D , Fowkes F G , Dawes J , Donnan P T , Lennie S E , Housley E 
Published: June 2012

BACKGROUND
Increased blood and plasma viscosity, hematocrit, fibrinogen, and activation of coagulation and leukocytes have been reported in patients with claudication; however, their associations with symptomatic and asymptomatic peripheral arterial disease have not been reported in an epidemiological study.

METHODS AND RESULTS
Blood and plasma viscosity, hematocrit, fibrinogen, urinary fibrinopeptide A, plasma leukocyte elastase, and uric acid were measured in a random sample of 1,581 men and women aged 55-74 years in Edinburgh, Scotland, and related to peripheral arterial stenosis (ankle-brachial systolic pressure index, ABPI) and to lower limb ischemia (intermittent claudication and reactive hyperemia test). Each variable (except fibrinopeptide A) was significantly related to prevalent symptomatic and asymptomatic peripheral arterial disease. On multivariate analysis, blood viscosity (p < 0.05) and fibrinogen (p < 0.01) were independently associated with peripheral arterial narrowing (ABPI); a positive interaction was found between fibrinogen and smoking in the association with ABPI. Plasma viscosity was associated with claudication in the presence of a given degree of arterial narrowing (odds ratio of claudication in top quintile compared with bottom quintile of plasma viscosity, 3.35; 95% CI, 1.32, 8.51). Leukocyte elastase and uric acid were each associated with reactive hyperemia independently of arterial narrowing (p < 0.01).

CONCLUSIONS
Blood rheological factors and leukocyte activation as well as arterial narrowing are associated with lower limb ischemia in the general population and may be implicated in its pathogenesis.
Silent ischemia in unstable angina is related to an altered cardiac norepinephrine handling.
Authors: Neri Serneri G G , Boddi M , Arata L , Rostagno C , Dabizzi P , Coppo M , Bini M , Lazzerini S , Dagianti A , Gensini G F 
Published: June 2012

BACKGROUND
Inferential evidence suggests that silent ischemia might be related to sympathetic activity. Study of [3H]norepinephrine kinetics is a suitable tool to assess the regional sympathetic activity. This method was applied to investigate whether silent myocardial ischemia in unstable angina is related to and depends on cardiac sympathetic overactivity.

METHODS AND RESULTS
Patients with active unstable angina were compared with patients with inactive unstable angina, stable effort angina, and controls. Silent myocardial ischemia was evaluated by three 24-hour Holter monitoring periods on alternate days, and [3H]norepinephrine kinetics was assessed under rest conditions and following the cold pressor test. Simultaneously, catecholamine concentrations were measured in the aortic, coronary sinus, and peripheral venous blood. Different than the other groups (p = 0.0013), in patients with active unstable angina, the majority of silent ischemic episodes occurred without increase in heart rate. These patients had a positive coronary sinus-aorta norepinephrine gradient, both at rest and following the cold pressor test. [3H]Norepinephrine kinetics demonstrated an increased selective cardiac spillover, both at rest and, even more, after the cold pressor test. Reduced cardiac [3H]norepinephrine extraction also was found. A significant relation was found between the number of ischemic episodes or the overall duration of silent ischemia and norepinephrine spillover, both at rest and following cold application.

CONCLUSIONS
During the acute phase of unstable angina (but not in the quiescent phase or in stable effort angina), a disorder in cardiac norepinephrine handling occurs. This results in a reflex cardiac sympathetic overactivity that plays a major role in the occurrence of silent myocardial ischemia.