Abstract:
BACKGROUND:This study examines the cellular basis for the phenotypic appearance of broad-based T waves, increased transmural dispersion of repolarization (TDR), and torsade de pointes (TdP) induced by beta-adrenergic agonists under conditions mimicking the LQT1 form of the congenital long-QT syndrome. METHODS AND RESULTS:A transmural ECG and transmembrane action potentials from epicardial, M, and endocardial cells were recorded simultaneously from an arterially perfused wedge of canine left ventricle. Chromanol 293B, a specific IKs blocker, dose-dependently (1 to 100 micromol/L) prolonged the QT interval and action potential duration (APD90) of the 3 cell types but did not widen the T wave, increase TDR, or induce TdP. Isoproterenol 10 to 100 nmol/L in the continued presence of chromanol 293B 30 micromol/L abbreviated the APD90 of epicardial and endocardial cells but not that of the M cell, resulting in widening of the T wave and a dramatic accentuation of TDR. Spontaneous as well as programmed electrical stimulation (PES)-induced TdP was observed only after exposure to the IKs blocker and isoproterenol. Therapeutic concentrations of propranolol (0.5 to 1 micromol/L) prevented the actions of isoproterenol to increase TDR and to induce TdP. Mexiletine 2 to 20 micromol/L abbreviated the APD90 of M cells more than that of epicardial and endocardial cells, thus diminishing TDR and the effect of isoproterenol to induce TdP. CONCLUSIONS:This experimental model of LQT1 indicates that a deficiency of IKs alone does not induce TdP but that the addition of beta-adrenergic influence predisposes the myocardium to the development of TdP by increasing transmural dispersion of repolarization, most likely as a result of a large augmentation of residual IKs in epicardial and endocardial cells but not in M cells, in which IKs is intrinsically weak. Our data provide a mechanistic understanding of the cellular basis for the therapeutic actions of beta-adrenergic blockers in LQT1 and suggest that sodium channel block with class IB antiarrhythmic agents may be effective in suppressing TdP in LQT1, as they are in LQT2 and LQT3, as well as in acquired (drug-induced) forms of the long-QT syndrome.
journal_name
Circulationjournal_title
Circulationauthors
Shimizu W,Antzelevitch Cdoi
10.1161/01.cir.98.21.2314subject
Has Abstractpub_date
1998-11-24 00:00:00pages
2314-22issue
21eissn
0009-7322issn
1524-4539journal_volume
98pub_type
杂志文章相关文献
CIRCULATION文献大全abstract::Hypertrophic cardiomyopathy (HCM) or idiopathic hypertrophic subaortic stenosis (IHSS) has been defined as an autosomal dominant myocardial disease characterized by specific physical findings, echocardiographic features, asymmetric septal hypertrophy and disordered myocardial architecture. Echocardiographic and scinti...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.55.6.901
更新日期:1977-06-01 00:00:00
abstract:BACKGROUND:Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing protein. Downstream of gp130, two signal-transducing pathways have been recognized, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the Ras-mitogen-activated protein kinase (MAPK) pathway. To d...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.94.10.2626
更新日期:1996-11-15 00:00:00
abstract::Composite graft replacement of the ascending aorta and aortic valve was performed in 78 patients over an 8 1/2-year period. Degenerative lesions of the aortic root in Marfan's syndrome (annuloaortic ectasia) was the indication for operation in 56 cases; the other 22 patients had other causes of aortic root dilatation ...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract:BACKGROUND:Myocardial necrosis can occur during percutaneous coronary intervention (PCI) despite optimal adjunctive pharmacology and careful technique. We investigated the mechanisms of procedural infarction using angiographic analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance imaging. METH...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCULATIONAHA.105.593210
更新日期:2006-08-15 00:00:00
abstract:BACKGROUND:The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known. METHODS AND RESULTS:Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) < or =35% and aortic stenosis with trans...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.101.16.1940
更新日期:2000-04-25 00:00:00
abstract:BACKGROUND:Supply of sulfhydryl groups with the administration of N-acetylcysteine (NAC) has been reported to reverse tolerance to nitroglycerin but not to isosorbide dinitrate (ISDN). Lack of interaction between NAC and ISDN was suggested as an explanation for these findings. The present study was therefore designed t...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.89.6.2595
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the s...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.86.3.878
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND:In myocardial cells, relaxation is governed primarily by the sarcoplasmic reticulum (SR) Ca(2+)-ATPase transporting enzyme, which regulates Ca2+ sequestration into the SR. Human and experimental cardiomyopathies are associated with reduced SR Ca(2+)-ATPase activity. METHODS AND RESULTS:To modify intracellul...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.2.423
更新日期:1997-01-21 00:00:00
abstract:BACKGROUND:Coronary perforation is a life-threatening complication of percutaneous interventions. In the past few years, the implantation of covered stents has emerged as a strategy for treatment when the traditional conservative approach (ie, prolonged balloon inflation and reversal of anticoagulation) fails. METHODS...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.102.25.3028
更新日期:2000-12-19 00:00:00
abstract:BACKGROUND:High-altitude pulmonary edema (HAPE) is characterized by pulmonary hypertension, increased pulmonary capillary permeability, and hypoxemia. Treatment is limited to descent to lower altitude and administration of oxygen. METHODS AND RESULTS:We studied the acute effects of inhaled nitric oxide (NO), 50% oxyge...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.98.22.2441
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND:The Fick principle (cardiac output = oxygen uptake ( O2)/systemic arterio-venous oxygen difference) is used to determine cardiac output in numerous clinical situations. However, estimated rather than measured O2 is commonly used because of complexities of the measurement, though the accuracy of estimation re...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.113.003334
更新日期:2014-01-14 00:00:00
abstract::The two-dimensional echocardiographic features of three patients with congenital aneurysms of the left atrium are described. The aneurysm arose from the left atrial appendage in two patients and from the posterior left atrial wall in one. The aneurysms were characterized by their origin from an otherwise normal left a...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.66.5.1065
更新日期:1982-11-01 00:00:00
abstract::The current dispute over the effects of "low" vs "high" doses of aspirin should take into consideration the pharmacokinetics of this drug. In fact, different pharmaceutical formulations of aspirin may deliver little or no aspirin to the systemic blood. This was the case, for instance, in healthy volunteers taking 320 ...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/01.cir.72.6.1185
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND:Hemodynamic stability after Norwood palliation often requires manipulation of pulmonary vascular resistance to alter the pulmonary-to-systemic blood flow ratio (Qp:Qs). Qp:Qs is often estimated from arterial saturation (SaO2), a practice based on 2 untested assumptions: constant systemic arteriovenous O2 dif...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.22.2699
更新日期:2001-06-05 00:00:00
abstract:BACKGROUND:The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in human cardiac hypertrophy and heart failure. Methods and Results- NEP mRNA was quantitated by real-time polymerase chain reaction (PCR) in left ventricular biopsies f...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc0302.103593
更新日期:2002-01-22 00:00:00
abstract:BACKGROUND:Adhesion of monocytes to the endothelium is an initial step in the early stages of atherosclerosis and inflammation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates a range of functional activities of monocytes, including regulation of monocyte adhesion and induction of cytokine producti...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.93.6.1185
更新日期:1996-03-15 00:00:00
abstract::We assessed factors during an initial episode of ventricular fibrillation that may be predictive of recurrence. Of 141 consecutive patients with acute ischemic heart disease who survived an initial episode of ventricular fibrillation, 41 (29%) had recurrent ventricular fibrillation during hospitalization. The incidenc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.64.6.1163
更新日期:1981-12-01 00:00:00
abstract:BACKGROUND:The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs. METHODS:Epigenetically controlled lncRNAs in human umbilical vein endothelia...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.116.026991
更新日期:2017-07-04 00:00:00
abstract:BACKGROUND:Assessment of systemic right ventricular (RV) function is a key point in the follow-up of patients with transposition of the great arteries (TGA). Current echocardiographic assessment of RV function is at best an estimate, and cardiac magnetic resonance (CMR) is considered the gold standard. However, this te...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000147284.54140.73
更新日期:2004-11-16 00:00:00
abstract::The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased betwee...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.80.4.853
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND:Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease-related death in relation to an underlying inflammatory response. METHODS AND RESULT...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.103.24.2915
更新日期:2001-06-19 00:00:00
abstract:BACKGROUND:Morbidity and mortality after conventional repair of thoracoabdominal aneurysms remain high. Alternative techniques have been proposed and are the subject of this report. METHODS AND RESULTS:Endovascular grafts that have a means of incorporating the visceral vessels into the aortic repair were divided into ...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/CIRCULATIONAHA.107.716134
更新日期:2008-04-29 00:00:00
abstract:BACKGROUND:Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy f...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.109.928903
更新日期:2010-07-13 00:00:00
abstract::A Y-shaped lesion in the right atrium allows induction of atrial flutter in dogs. We recorded the activation sequence during this tachycardia from 96 endocardial bipolar electrodes using intracavitary electrode arrays during 12 separate episodes in three isolated perfused hearts. In each case a reentrant impulse circu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.76.5.1155
更新日期:1987-11-01 00:00:00
abstract:BACKGROUND:Cardiovascular disease is the leading cause of death for both men and women in the United States and the world. A profound pattern exists in the time of day at which the death occurs; it is in the morning, when the endothelium is most vulnerable and blood pressure surges, that stroke and heart attack most fr...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.827477
更新日期:2009-03-24 00:00:00
abstract::Although laparoscopic surgery accounts for >2 million surgical procedures every year, the current preoperative risk scores and guidelines do not adequately assess the risks of laparoscopy. In general, laparoscopic procedures have a lower risk of morbidity and mortality compared with operations requiring a midline lapa...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.116.023262
更新日期:2017-02-14 00:00:00
abstract:BACKGROUND:Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reporte...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.118.035931
更新日期:2019-01-29 00:00:00
abstract:BACKGROUND:Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.117.028021
更新日期:2018-01-16 00:00:00
abstract::Although for most children the process of atherosclerosis is subclinical, dramatically accelerated atherosclerosis occurs in some pediatric disease states, with clinical coronary events occurring in childhood and very early adult life. As with most scientific statements about children and the future risk for cardiovas...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/CIRCULATIONAHA.106.179568
更新日期:2006-12-12 00:00:00
abstract::Mapping of blood velocities across the lumen of the ascending aorta was performed in eight patients during open-heart surgery. A Doppler ultrasound probe was constructed to measure velocities in 2 mm steps from the maximum convexity to the maximum concavity of aorta, 6 to 7 cm above the aortic valve. In five patients ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.76.1.90
更新日期:1987-07-01 00:00:00