Electrophysiological remodeling in hypertrophy and heart failure

Tomaselli, Gordon F.

doi:10.1016/s0008-6363(99)00017-6

Cited by 674 publications

(553 citation statements)

References 161 publications

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“…Prolongation of APDs has been commonly observed in ventricular cells isolated from failing hearts of various animal species including human and cardiomyopathic hamsters. [3][4][5][6][7] In this study, APDs in untreated BIO 14.6 myocytes were significantly longer than those in normal F1␤ myocytes. A decrease in I Ca,L is expected to shorten APD, whereas a decrease in I to , I K , or I K1 is expected to prolong APD.…”

Section: Matsumoto Et Al Et a Receptor Blockade On Electrical Remodelingmentioning

confidence: 81%

“…2 Numerous studies that used cardiomyocytes of failing hearts have indicated that a variety of K ϩ currents are downregulated and the action potential duration is prolonged. [3][4][5][6][7] Heterogeneous prolongation of the action potential can lead to the dispersion of refractoriness and the occurrence of ventricular reentrant arrhythmias. However, medical therapy to prevent such electrophysiological alterations associated with heart failure has not been established.…”

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confidence: 99%

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Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

Matsumoto

Aihara²,

Yamauchi-Kohno³

et al. 2002

Circulation

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Background-The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET A receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.6 cardiomyopathic hamsters. Methods and Results-Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1␤ hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET A receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca 2ϩ current (I Ca,L ), the transient outward current (I to ), the delayed rectifier K ϩ current (I K ), and the inward rectifier K ϩ current (I K1 ) were decreased compared with those of F1␤ hamsters. Long-term treatment with the ET A receptor antagonist significantly attenuated action potential duration prolongation and reduction of I to , I K , and I Ca,L in BIO 14.6 ventricular cells. Long-term ET A receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters. Conclusions-Long-term treatment with an ET

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Section: Matsumoto Et Al Et a Receptor Blockade On Electrical Remodelingmentioning

confidence: 81%

mentioning

confidence: 99%

Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

Matsumoto

Aihara²,

Yamauchi-Kohno³

et al. 2002

Circulation

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“…Our electrophysiological data support the possibility that similar alterations occur in the STZ‐hyperglycemic mouse model employed here. Importantly, reduction in the outward K + Kv currents and prolongation of AP duration in mammals appear to be a conserved response to a variety of physio‐ and pathological conditions dictated by an increase in workload of the myocardium, including ischemic cardiomyopathy,60, 61 hypertension,62 pressure overload,63 aging,20, 64 and heart failure 18, 65, 66. Thus, the enhanced beat‐to‐beat variability observed in diabetic myocytes may represent a feature shared with other diseased conditions.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Meo

Meste

Signore

et al. 2016

JAHA

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BackgroundDiabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization.Methods and ResultsDiabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K+ and L‐type Ca2+ currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes.ConclusionsReductions in the repolarizing K+ currents may contribute to electrical disturbances of the diabetic heart.

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confidence: 99%

“…The mechanisms underlying ventricular arrhythmogenesis in electrically remodeled failing hearts are not fully understood (32,44). Studies have consistently found prolongation of cardiac action potential (AP) duration (APD) in myocardial tissues and/or cells from different models of experimental HF (26,44) and from explanted tissues of humans with terminal HF (3). Abnormalities in repolarization can predispose to dispersion of repolarization, leading to nonexcitable gap reentry (6), and AP prolongation also favors the development of early afterdepolarizations (EADs), which can induce triggered arrhythmias (9).…”

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confidence: 99%

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

Lau

Ducharme

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

225

187

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action potential and ionic current remodeling in ventricles of failing canine hearts. Am J Physiol Heart Circ Physiol 283: H1031-H1041, 2002. First published May 30, 2002 10.1152/ ajpheart.00105.2002.-Heart failure (HF) produces important alterations in currents underlying cardiac repolarization, but the transmural distribution of such changes is unknown. We therefore recorded action potentials and ionic currents in cells isolated from the endocardium, midmyocardium, and epicardium of the left ventricle from dogs with and without tachypacing-induced HF. HF greatly increased action potential duration (APD) but attenuated APD heterogeneity in the three regions. Early afterdepolarizations (EADs) were observed in all cell types of failing hearts but not in controls. Inward rectifier K ϩ current (IK1) was homogeneously reduced by ϳ41% (at Ϫ60 mV) in the three cell types. Transient outward K ϩ current (Ito1) was decreased by 43-45% at ϩ30 mV, and the slow component of the delayed rectifier K ϩ current (IKs) was significantly downregulated by 57%, 49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells, whereas the rapid component of the delayed rectifier K ϩ current was not altered. The results indicate that HF remodels electrophysiology in all layers of the left ventricle, and the downregulation of IK1, Ito1, and IKs increases APD and favors occurrence of EADs. heterogeneity; early afterdepolarizations; congestive heart failure; arrhythmias

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Electrophysiological remodeling in hypertrophy and heart failure

Cited by 674 publications

References 161 publications

Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

Long-Term Endothelin A Receptor Blockade Inhibits Electrical Remodeling in Cardiomyopathic Hamsters

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Transmural action potential and ionic current remodeling in ventricles of failing canine hearts

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