bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use-dependent block of the pacemaker current I(f) in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors.
Authors: Goethals M , Raes A , van Bogaert P P 
Published: June 2012

BACKGROUND
Zatebradine (UL-FS 49) is a drug with a specific bradycardiac electrophysiological profile. It reduces heart rate by lengthening the duration of diastolic depolarization in the sinoatrial (SA) node. The ionic basis of this action, however, is not clarified.

METHODS AND RESULTS
We used the whole-cell patch-clamp technique to study the effects of zatebradine on ionic currents underlying diastolic depolarization of isolated rabbit SA node cells. Low concentrations of zatebradine simultaneously reduced diastolic depolarization rate and the pacemaker current I(f). The drug blocked the pacemaker current, I(f), in a use-dependent manner without causing a shift of its activation curve. At hyperpolarized potentials, unblock of I(f) occurred. Clinically relevant concentrations of the drug have little effect on the L-type calcium current or delayed rectifier potassium current.

CONCLUSIONS
This use-dependent block of the If channel can account for most of the pharmacological characteristics of zatebradine and is probably the mechanism of heart rate reduction caused by this agent. Thus, the sinus node inhibitor zatebradine belongs to a new class of "I(f) blockers" with possible advantages over currently available drugs for the treatment of ischemic heart disease.
Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina. A clue to the mechanism of transformation from the stable to the unstable clinical state.
Authors: Flugelman M Y , Virmani R , Correa R , Yu Z X , Farb A , Leon M B , Elami A , Fu Y M , Casscells W , Epstein S E 
Published: June 2012

BACKGROUND
The mechanisms responsible for the transformation of stable angina to unstable angina, a major cause of morbidity and mortality, are commonly believed to be plaque rupture and thrombosis. We determined whether additional mechanisms are operative by analyzing the histopathology and immuno-histopathology of coronary plaques retrieved by directional atherectomy of patients with unstable angina in whom no intraluminal thrombus was demonstrated by angiography.

METHODS AND RESULTS
The histological findings of atherectomy specimens from 34 patients with unstable angina were compared with those of 24 patients with postangioplasty restenosis, whose lesions are known to be composed of smooth muscle cells (SMCs), and 10 patients with stable angina, whose lesions contain relatively few SMCs. We also studied the expression of acidic and basic fibroblast growth factors (aFGF and bFGF), whose role in the vascular response to injury has been established. Specimens from unstable angina resembled those from postangioplasty restenosis in regard to SMC abundance (scale, 0 to 3; 1.4 +/- 0.9 versus 1.7 +/- 0.9; P = NS), and both differed from those of stable angina. Thrombus and/or hemorrhage occurred in only 34% of patients with unstable angina (compared with 8% of restenosis patients and in none of stable angina patients). Active lesions (defined as lesions (defined as lesions containing one or more of the following: thrombus, hemorrhage, abundant and disorganized SMCs in the presence of loose connective tissue, or inflammatory infiltrate) were observed in 56% of the unstable angina patients and in 50% of the restenosis patients but in none of the stable angina patients. The expression of aFGF and bFGF was detected in 80% to 100% of unstable angina (n = 11) and restenosis (n = 10) specimens but in only 1 of 5 stable angina specimens.

CONCLUSIONS
Microscopic evidence of thrombosis and plaque rupture occurred in only one third of unstable angina patients, selected because they had no angiographic evidence of intracoronary thrombus. Moreover, their lesions resembled those of restenosis patients in regard to SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our findings therefore suggest that an alternative mechanism to plaque rupture and thrombus formation may be operative in the precipitation of unstable angina; namely, in a subset of patients, SMC proliferation may lead to gradual plaque expansion and thereby to lumenal narrowing and unstable angina. Our data also suggest a role for aFGF and bFGF in this process.
Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.
Authors: Melandri G , Semprini F , Cervi V , Candiotti N , Palazzini E , Branzi A , Magnani B 
Published: June 2012

BACKGROUND
Patients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris.

METHODS AND RESULTS
According to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P = .035) and an improvement in both the time to 1-mm ST segment depression (P = .008) and the peak ST segment depression (P = .015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P = .016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P = .0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding.

CONCLUSIONS
Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.
The role of transesophageal echocardiography in identifying anomalous coronary arteries.
Authors: Fernandes F , Alam M , Smith S , Khaja F 
Published: June 2012

BACKGROUND
The study objective was to evaluate the role of transesophageal echocardiography in identifying the origin of anomalous coronary arteries and confirming their course in relation to the great vessels. The diagnosis of coronary anomalies is made by angiography. The anomalous left main artery with a course between the pulmonary artery and the aorta has been associated with myocardial infarction and sudden death. The course of these anomalous coronary arteries is difficult to demonstrate by angiography alone.

METHODS AND RESULTS
Nine patients with angiographically confirmed anomalous coronary arteries were studied by transesophageal echocardiography with color flow Doppler. The abnormal origin of the anomalous coronary arteries was confirmed by transesophageal echocardiography in all nine patients. In four patients, the left main coronary artery originated from the right sinus of Valsalva. In all of these patients, transesophageal echocardiography demonstrated the course of the anomalous left main coronary artery between the aorta and pulmonary artery better than angiography. Other anomalies that were visualized included two patients with origin of the right coronary arteries from the left aortic sinus, one patient with origin of the left anterior descending from the right sinus, one patient with origin of circumflex from the right sinus, and one patient with origin of the left main coronary artery from the pulmonary artery.

CONCLUSIONS
Transesophageal echocardiography is a useful noninvasive test for diagnosing anomalous origin of the coronary arteries. Furthermore, it is a valuable adjunct to angiography in demonstrating the abnormal course of the left main coronary artery interposed between the aorta and the pulmonary artery, a potentially life-threatening entity.
Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential.
Authors: Nakagawa H , Beckman K J , McClelland J H , Wang X , Arruda M , Santoro I , Hazlitt H A , Abdalla I , Singh A , Gossinger H 
Published: June 2012

BACKGROUND
Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) with right bundle branch block configuration and left-axis deviation has been suggested to originate from the left posterior fascicle. The purpose of this study was to determine how frequently potentials generated by the Purkinje fiber network (P potential) can be recorded preceding ventricular activation, and the role of the P potential in guiding radiofrequency catheter ablation.

METHODS AND RESULTS
Eight patients (mean age, 26 +/- 10 years) with ILVT (cycle length, 346 +/- 59 milliseconds) were studied. Right and left ventricular endocardial mapping during tachycardia identified earliest ventricular activation at the posteroapical left ventricular septum. In all patients, earliest ventricular activation during tachycardia was preceded by a distinct potential. This potential also preceded ventricular activation during sinus rhythm, consistent with activation of a segment of the left posterior fascicle (P potential). The earliest recorded P potential preceded the QRS during tachycardia by 15 to 42 milliseconds (mean, 27 +/- 9 milliseconds). The application of radiofrequency current at 1 to 4 sites (median, 1) eliminated ILVT in all eight patients. In the seven patients with P potentials recorded at multiple sites within the posteroapical septum, ablation was successful at the site of the earliest P potential and unrelated to the timing of ventricular activation. In the remaining patient, ablation was successful at a site recording a late P potential fusing with earliest ventricular activation. During follow-up (1 to 67 months; median, 10.5) ILVT recurred only in the latter patient. Pace mapping during tachycardia at the successful ablation site in four patients produced a similar QRS with stimulus-QRS interval equal to P-QRS interval during tachycardia. However, a similar QRS was obtained by pacing at nearby sites that recorded a later P potential.

CONCLUSIONS
These findings support the hypothesis that ILVT originates from the Purkinje network of the left posterior fascicle. A P potential can be recorded at the posteroapical left ventricular septum during ILVT, and ablation is successful at the site recording the earliest P potential. Pace mapping with similar QRS is not specific due to capture of the Purkinje fiber network at a site remote from the origin of the tachycardia.
Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B.
Authors: Zhao X Q , Brown B G , Hillger L , Sacco D , Bisson B , Fisher L , Albers J J 
Published: June 2012

BACKGROUND
Do the benefits of intensive lipid-lowering therapy seen in symptomatic patients extend to high-risk subjects who have never had symptoms?

METHODS AND RESULTS
Of 120 men completing the FATS trial, 91 were symptomatic and 29 asymptomatic. All had apolipoprotein B > or = 125 mg/dL, a positive family history, and coronary atherosclerosis. All were counseled in diet and randomized to intensive therapy: colestipol 10 g TID plus either niacin 1 g QID or lovastatin 20 mg BID or to conventional therapy: placebos, or colestipol if low-density lipoprotein cholesterol was elevated. End points included quantitative arteriographic disease change and clinical events over a 2.5-year interval. At baseline, symptomatic and asymptomatic patients had comparable risk profiles, but proximal stenosis severity averaged 36% for symptomatic and 23% for asymptomatic patients (P < .001). Among the 91 symptomatic patients, those in the intensive group experienced definite (> or = 10%S) proximal lesion progression less frequently than conventional (24% of intensive versus 48% of conventional) and definite regression more frequently (36% of intensive versus 15% of conventional) (P = .009). Similarly, among the 29 asymptomatic patients, 19% of intensive versus 38% of conventional had progression and 31% of intensive versus 0% of conventional, regression (P = .04). Ischemia on baseline exercise tolerance testing was associated with significantly greater proximal disease progression among the asymptomatic patients. Clinical cardiovascular events (death, infarction, or revascularization) occurred in 10 of 38 symptomatic patients originally assigned to conventional therapy, compared with 5 of 76 symptomatic patients assigned to intensive (P < .01); no asymptomatic patient had an event.

CONCLUSIONS
Asymptomatic subjects with this high-risk profile have less coronary disease at baseline than comparable symptomatic patients, and they have an excellent short-term clinical prognosis. However, asymptomatic subjects are indistinguishable from symptomatic patients in terms of their arterial disease progression with conventional therapy and their regression with intensive. These findings may justify an active treatment strategy in such subjects, particularly those with provokable ischemia.
Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.
Authors: Demirovic J , Nabulsi A , Folsom A R , Carpenter M A , Szklo M , Sorlie P D , Barnes R W 
Published: June 2012

BACKGROUND
Although much has been written in recent years about the relation between alcohol and atherosclerotic disease, controversy exists as to whether and how alcohol exerts an effect on atherosclerosis in different sites.

METHODS AND RESULTS
We tested the hypothesis that alcohol consumption is associated inversely with carotid atherosclerosis in a population sample of 45- to 64-year-old men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study and were free of cardiovascular disease at a baseline examination in 1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal-medial wall thickness and distensibility as indices of the degree of atherosclerosis. The level of alcohol consumption in the ARIC sample was generally low. Age-adjusted mean values of alcohol consumed (grams per week) were 72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite women. After adjustments for age, artery depth, education, body mass index, sport index, cigarette-years of smoking, low-density lipoprotein cholesterol, and diabetes mellitus, there was no significant cross-sectional association of reported current alcohol intake with either carotid artery wall thickness (among white and nonwhite men and nonwhite women) or distensibility (in any of the four sex-race groups). Among white women, the adjusted mean value of carotid artery wall thickness tended to be higher in light to moderate drinkers than in never or rare drinkers, but the difference across drinking status categories was of borderline statistical significance (P = .04) and may be of little biological importance.

CONCLUSIONS
The ARIC Study found no material cross-sectional association between current alcohol intake and carotid atherosclerosis but provides an opportunity in the future to study atherosclerosis progression and incident events in relation to alcohol consumption in a large population sample of men and women.
Effects of different training intensities on 24-hour blood pressure in hypertensive subjects.
Authors: Marceau M , Kouamé N , Lacourcière Y , Cléroux J 
Published: June 2012

BACKGROUND
It is generally accepted that physical training decreases blood pressure in hypertensive subjects, but the importance of training intensity has not been established. This study compared the effects of endurance training at different intensities on ambulatory blood pressure and on blood pressure load (percentage of readings above 140/90 and 120/80 mm Hg during the waking and sleeping periods, respectively).

METHODS AND RESULTS
Previously sedentary subjects with mild to moderate hypertension were evaluated in a crossover fashion according to a Latin square after a sedentary control period and after training at low and at moderate intensity corresponding to 50% and 70% of maximal oxygen uptake, respectively. Each period lasted 10 weeks. After training at moderate intensity, a higher maximal oxygen uptake was found compared with sedentary values but not after training at low intensity. Both training intensities exerted a similar antihypertensive effect of about 5 mm Hg for systolic and diastolic 24-hour blood pressures. However, training at low intensity reduced blood pressure exclusively during the walking hours, whereas training at a moderate intensity reduced blood pressure only during the evening and sleeping hours. Waking blood pressure load decreased from 66% to 49% after training at low intensity, whereas sleeping blood pressure load decreased from 61% to 34% after training at moderate intensity (both P < .05).

CONCLUSIONS
Low- and moderate-intensity training produce similar 24-hour blood pressure reductions, but each training intensity may interfere with different pathogenic effects associated with different blood pressure profiles.
Electrical and mechanical alternans in canine myocardium in vivo. Dependence on intracellular calcium cycling.
Authors: Hirayama Y , Saitoh H , Atarashi H , Hayakawa H 
Published: June 2012

BACKGROUND
Electrical and mechanical alternans are thought to result from a common cellular mechanism. To confirm this phenomenon in vivo and extend our understanding, we investigated the effects of temperature, verapamil, and caffeine on alternans in intact beating hearts.

METHODS AND RESULTS
We recorded surface ECG, monophasic action potential (MAP) using suction electrodes, and left ventricular pressure (LVP). Alternans of MAP configurations and of LVP were evaluated in 20 dogs. MAPs were recorded from the apex, base, and midportion of the left ventricle with LVP. The hearts were driven from the left ventricular apex at a basic cycle length of 1000 milliseconds, and alternans was induced with an abrupt shortening of the cycle length to 400 milliseconds. MAPD30/100, the ratio between the MAP durations (MAPD) at 30% and 100% repolarization levels, was measured as an index of MAP configuration. The magnitude of MAP or LVP alternans was defined as the difference in MAPD30/100 or in LVP between the fifth and sixth paced beats. The magnitude of MAP alternans differed by recording site but correlated with activation time. Lowering the temperature increased the magnitude. MAP alternans was always associated with LVP alternans under control conditions. Verapamil significantly attenuated the magnitude of MAP alternans but did not change that of LVP alternans. Caffeine attenuated the magnitude of both MAP and LVP alternans. T wave alternans was suppressed by verapamil or caffeine.

CONCLUSIONS
Activation time is one of the factors modifying electrical alternans. Delayed intracellular Ca2+ cycling plays a role in the concomitant occurrence of electrical and mechanical alternans.
Differences in the electrophysiological response of canine ventricular epicardium and endocardium to ischemia. Role of the transient outward current.
Authors: Lukas A , Antzelevitch C 
Published: June 2012

BACKGROUND
Acute ischemia is known to produce more severe electrophysiological disturbances in canine ventricular epicardium than endocardium, although the mechanism for the differential sensitivity is still unresolved. Recent studies have demonstrated the presence of a prominent transient outward current (Ito) in ventricular epicardium but not endocardium. The present study was designed to test the hypothesis that the differential sensitivity of these two tissues to ischemia results, at least in part, from a more prominent Ito in epicardium than in endocardium.

METHODS AND RESULTS
Isolated canine ventricular epicardial and endocardial tissues and myocytes were studied by standard microelectrode techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished the action potential plateau and caused a 50% to 60% shortening of action potential duration in epicardium but only a 10% to 20% shortening in endocardium. 4-Aminopyridine, an Ito inhibitor, restored the plateau in epicardium and reduced the dispersion of action potential duration between epicardium and endocardium. Stimulation protocols that minimized the contribution of Ito, such as acceleration of the stimulation rate or introduction of early premature beats, produced a paradoxical prolongation of the epicardial response caused by restoration of the action potential dome. Thus, ischemia-induced dispersion of repolarization was greatly diminished at rapid rates and after premature beats. Similar results were obtained in tissues and myocytes obtained from the same myocardial layers, suggesting that the differential sensitivities of epicardium and endocardium to ischemia are largely a result of inherent differences in cellular properties.

CONCLUSIONS
Our data suggest that the presence of a prominent Ito in epicardium but not endocardium contributes importantly to the selective electrical depression of epicardium by simulated ischemia. The repolarizing influence of Ito serves to amplify the ischemia-induced changes in inward (ICa and INa) and outward (calcium-activated) currents. By facilitating loss of the dome in epicardium, Ito contributes to the development of a marked dispersion of repolarization between normal and ischemic epicardium and between epicardium and endocardium, thereby providing the electrophysiological substrate for the genesis of reentrant arrhythmias.