Short-term hypertension is associated with the development of atrial fibrillation substrate: A study in an ovine hypertensive model

Lau, Dennis H.; Mackenzie, Lorraine; Kelly, Darren J.; Psaltis, Peter J.; Worthington, Michael; Rajendram, Arumuga; Kelly, Douglas; Nelson, Adam; Zhang, Yuan; Kuklik, Paweł; Brooks, A.; Worthley, Stephen G.; Faull, Randall J.; Rao, M. Mohan; Edwards, James; Saint, David A.; Sanders, Prashanthan

doi:10.1016/j.hrthm.2009.11.031

Cited by 89 publications

(81 citation statements)

References 30 publications

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“…17 Open-chest rat electrophysiology study was undertaken under general anesthesia, with a 128-electrode biatrial plaque (5-mm interelectrode distance). 17,18 EGMs were sampled at 1000 Hz, and filtered from 30 to 500 Hz (Laboratory System Pro, Bard Electrophysiology). AF episodes lasting >20 seconds induced with rapid atrial pacing were selected for study.…”

Section: Sheep Modelmentioning

confidence: 99%

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Ganesan

Kuklik

Lau

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background-The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results-Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles).The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions-ShEn is a mechanistically based tool that may assist AF rotor mapping. (Circ Arrhythm Electrophysiol.2013;6:48-57.)

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Section: Sheep Modelmentioning

confidence: 99%

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Ganesan

Kuklik

Lau

et al. 2013

Circ: Arrhythmia and Electrophysiology

Self Cite

108

115

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“…21,22 Each annotation was manually verified with the local activation time annotated to the peak of the largest amplitude deflection on bipolar electrograms. Local conduction velocity was calculated from the local vectors within each triangle of electrodes as previously described.…”

Section: Atrial Conductionmentioning

confidence: 99%

“…Local conduction velocity was calculated from the local vectors within each triangle of electrodes as previously described. 21,22 A mean conduction velocity can then be derived.…”

Section: Atrial Conductionmentioning

confidence: 99%

Myocardial Infarction and Atrial Fibrillation

Alasady

Shipp

Brooks

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background— Myocardial infarction (MI) is associated with the development of atrial fibrillation (AF). We aimed to characterize the atrial abnormalities because of MI and determine the role of ischemia to the AF substrate. Methods and Results— Forty-four sheep were studied. MI was induced by occlusion of the left circumflex artery (LCX) or left anterior descending artery (LAD). Excluding 11 with fatal arrhythmias, equal groups of animals (LCX; LAD; and sham-operated) underwent sequential electrophysiology study for 45 minutes to determine atrial effective refractory periods, conduction velocity, conduction heterogeneity index, and AF inducibility. Postmortem evaluation was performed with 2,3,5 triphenyl tetrazolium chloride staining. MI resulted in greater left ventricular dysfunction ( P <0.05), LA pressure ( P <0.0003), and reduction in atrial effective refractory periods ( P <0.0001) compared with control. 2,3,5 triphenyl tetrazolium chloride staining demonstrated that the left circumflex artery, and not the LAD, group had atrial infarction. The left circumflex artery group demonstrated the following compared with the LAD or control groups: greater slowing in atrial conduction velocity ( P <0.0001 and P <0.001); increased absolute range of conduction phase delay ( P <0.001 and P <0.001); increased conduction heterogeneity index ( P <0.0001 and P <0.001); greater AF vulnerability ( P <0.05 for both); and longer AF duration ( P <0.05 for both). LAD group had modest but significant slowing in conduction velocity ( P <0.01) but no change in conduction heterogeneity index or AF duration compared with control. Conclusions— Left ventricular infarction, which is known to result in atrial stretch, hemodynamic change, and neurohumoral activation, contributes partially to the atrial abnormalities in MI. Atrial ischemia/infarction results in greater atrial electrophysiological changes and propensity for AF forming the dominant substrate for AF in MI.

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“…Hypertension is widely recognized as an important independent risk factor for AF (7,46). Animal models of hypertension have been shown to have significant structural and electrophysiological remodeling and increased atrial arrhythmia inducibility (19,24,49,53). However, the cellular mechanisms responsible for these effects remain poorly understood.…”

mentioning

confidence: 99%

Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure

Lader

Vásquez²,

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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of atrial ATPsensitive K ϩ channels in a model of salt-induced elevated blood pressure. Am J Physiol Heart Circ Physiol 301: H964 -H974, 2011. First published July 1, 2011; doi:10.1152/ajpheart.00410.2011.-Hypertension is associated with the development of atrial fibrillation; however, the electrophysiological consequences of this condition remain poorly understood. ATP-sensitive K ϩ (KATP) channels, which contribute to ventricular arrhythmias, are also expressed in the atria. We hypothesized that salt-induced elevated blood pressure (BP) leads to atrial KATP channel activation and increased arrhythmia inducibility. Elevated BP was induced in mice with a high-salt diet (HS) for 4 wk. High-resolution optical mapping was used to measure atrial arrhythmia inducibility, effective refractory period (ERP), and action potential duration at 90% repolarization (APD90). Excised patch clamping was performed to quantify KATP channel properties and density. KATP channel protein expression was also evaluated. Atrial arrhythmia inducibility was 22% higher in HS hearts compared with control hearts. ERP and APD90 were significantly shorter in the right atrial appendage and left atrial appendage of HS hearts compared with control hearts. Perfusion with 1 M glibenclamide or 300 M tolbutamide significantly decreased arrhythmia inducibility and prolonged APD90 in HS hearts compared with untreated HS hearts. KATP channel density was 156% higher in myocytes isolated from HS animals compared with control animals. Sulfonylurea receptor 1 protein expression was increased in the left atrial appendage and right atrial appendage of HS animals (415% and 372% of NS animals, respectively). In conclusion, KATP channel activation provides a mechanistic link between salt-induced elevated BP and increased atrial arrhythmia inducibility. The findings of this study have important implications for the treatment and prevention of atrial arrhythmias in the setting of hypertensive heart disease and may lead to new therapeutic approaches. action potentials; arrhythmia mechanisms; cardiac remodeling; potassium channel; salt sensitivity hypertension ATRIAL FIBRILLATION (AF) is the most prevalent cardiac arrhythmia and is a major risk factor for stroke, congestive heart failure, and mortality (8,33,46). Although remodeling in response to AF has been a subject of intense investigation (1, 62), relatively few studies have focused on the mechanisms responsible for the substrate changes that underlie the initiation of atrial tachyarrhythmias. Hypertension is widely recognized as an important independent risk factor for AF (7,46). Animal models of hypertension have been shown to have significant structural and electrophysiological remodeling and increased atrial arrhythmia inducibility (19,24,49,53). However, the cellular mechanisms responsible for these effects remain poorly understood. Importantly, the contribution of ATP-sensitive K ϩ (K ATP ) channel currents (I K,ATP ) to hypertensioninduced electrophysiological remodeling has not been investigated.K ATP ch...

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Short-term hypertension is associated with the development of atrial fibrillation substrate: A study in an ovine hypertensive model

Cited by 89 publications

References 30 publications

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Myocardial Infarction and Atrial Fibrillation

Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure

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Short-term hypertension is associated with the development of atrial fibrillation substrate: A study in an ovine hypertensive model

Cited by 89 publications

References 30 publications

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation

Myocardial Infarction and Atrial Fibrillation

Remodeling of atrial ATP-sensitive K+ channels in a model of salt-induced elevated blood pressure

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Remodeling of atrial ATP-sensitive K⁺ channels in a model of salt-induced elevated blood pressure