Left Ventricular Hypertrophy Decreases Slowly but Not Rapidly Activating Delayed Rectifier Potassium Currents of Epicardial and Endocardial Myocytes in Rabbits

Xu, Xiaoping; Rials, Seth J.; Wu, Ying; Salata, Joseph J.; Liu, Tengxian; Bharucha, David B.; Marinchak, Roger A.; Kowey, Peter R.

doi:10.1161/01.cir.103.11.1585

Cited by 77 publications

(68 citation statements)

References 29 publications

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“…A preliminary study (18) has reported that I Ks was reduced in cells from terminally failing human hearts compared with mildly diseased cells. In the present study, we found that I Ks , and not I Kr , was significantly reduced in all three regions, consistent with a recent report (48) in hypertrophic rabbit hearts in which only I Ks , not I Kr , was reduced in ventricular endocardial and epicardial cells. Our results showed that the percentage of I Ks reduction was greater in epicardial and endocardial cells than in midmyocardial cells, which may contribute in part to the inhomogeneous prolongation of APD in the three regions.…”

Section: Discussionsupporting

confidence: 93%

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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Section: Discussionsupporting

confidence: 93%

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

View full text Add to dashboard Cite

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“…In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells. In isolated single cells, the presence of a prominent I to current in epicardial and midmycardial myocytes gives rise to a notch following the upstroke of the action potential, which is absent in endocardial action potentials (Fig.…”

Section: Transmural Electrophysiological Heterogeneities In the Ventrsupporting

confidence: 78%

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

“…Experimental studies using isolated endocardial, midmyocardial and epicardial myocytes report transmural differences in I to in canine, rabbit, guinea pig and human (Li et al, 1998;McIntosh et al, 1998;Antzelevitch et al, 1999a, b), in I Na in canine (Antzelevitch et al, 1999a, b), in I Ks in canine and rabbit (Liu and Antzelevitch, 1995;Xu et al, 2001;Yan et al, 2001), and to a smaller extent, in I Kr in rabbit ). In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells.…”

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 99%

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The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Maharaj

Blake

Trayanova

et al. 2008

Progress in Biophysics and Molecular Biology

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Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.

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“…Risk factors, such as sex, 30,63,64 body mass index, 65,66 myocardial ischemia, 67,68 heart failure, 69,70 hypothermia, 71 and hypokalemia, 72,73 have been correlated with prolonged QT intervals in other studies.…”

Section: Risk Factors and Alqtsmentioning

confidence: 93%

Acquired Long QT Syndrome: Frequency, Onset, and Risk Factors in Intensive Care Patients

Kozik

Wung

2012

Critical Care Nurse

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Background Acquired long QT syndrome is a reversible condition that can lead to torsades de pointes and sudden cardiac death. Objective To determine the frequency, onset, frequency of medications, and risk factors for the syndrome in intensive care patients. Methods In a retrospective chart review of 88 subjects, hourly corrected QT intervals calculated by using the Bazett formula were collected. Acquired long QT syndrome was defined as a corrected QT of 500 milliseconds or longer or an increase in corrected QT of 60 milliseconds or greater from baseline level. Risk factors and medications administered were collected from patients’ medical records. Results The syndrome occurred in 46 patients (52%); mean time of onset was 7.4 hours (SD, 9.4) from time of admission. Among the 88 patients, 52 (59%) received a known QTc-prolonging medication. Among the 46 with the syndrome, 23 (50%) received a known QT-prolonging medication. No other risk factor studied was significantly predictive of the syndrome. Conclusions Acquired long QT syndrome occurs in patients not treated with a known QT-prolonging medication, indicating the importance of frequent QT monitoring of all intensive care patients.

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Left Ventricular Hypertrophy Decreases Slowly but Not Rapidly Activating Delayed Rectifier Potassium Currents of Epicardial and Endocardial Myocytes in Rabbits

Abstract: LVH induces a decrease in I(Ks) density and increases the propensity to develop early afterdepolarizations, especially in Endo.

Cited by 77 publications

References 29 publications

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

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

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Acquired Long QT Syndrome: Frequency, Onset, and Risk Factors in Intensive Care Patients

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