Ventricular rate determines early bradycardic electrical remodeling

Suto, Fumiaki; Zhu, Wei; Cahill, Sean A.; Greenwald, Ilana; Navarro, André L.C.; Gross, Gil J.

doi:10.1016/j.hrthm.2004.12.020

Cited by 9 publications

(23 citation statements)

References 32 publications

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“…Bradycardic pacing was maintained for 2 days in 11 rabbits and for 8 days in 13 rabbits. Steady-state QT i and whole cell patch-clamp data from 8 of these 13 rabbits that were reported previously (23) are not included here.…”

Section: Methodsmentioning

confidence: 99%

“…QT i measurements were obtained on day 0 and either on day 2 or on day 8 post-CHB induction from six-lead surface electrocardiograms recorded with a sampling interval of 1.2 ms in anesthetized animals (ketamine, 33 mg/kg; and acepromazine, 1.1 mg/kg iv) after at least 5 min of continuous pacing at 140 beats/min (23). Animals in the remodeling reversal protocol underwent ECG recording on days 0, 8, and 16.…”

Section: Methodsmentioning

confidence: 99%

“…RV myocytes were isolated as described elsewhere (23). Briefly, the excised heart was retrogradely perfused for 10 min with nominally Ca 2ϩ free HEPES-buffered saline (HBS).…”

Section: Methodsmentioning

confidence: 99%

“…Conventional whole cell patch clamp was performed as previously described (2,5,23). Delayed rectifier currents were measured as peak density of tail current elicited by repolarization to Ϫ30 mV following 3-s depolarizing voltage steps from a holding potential of Ϫ80 mV.…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratory (23) and others (27,28,30) have shown that downregulation of ventricular myocyte rapidly (I Kr ) and slowly (I Ks ) activating delayed rectifier repolarizing K ϩ currents underlies electrocardiographic QT interval (QT i ) prolongation and predisposition to torsades des pointes following at least 1 wk of bradycardia in animal models of ventricular electrical remodeling.…”

mentioning

confidence: 99%

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I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

Suto

Zhu²,

Chan³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Bradycardic ventricular electrical remodeling predisposes to lethal tachyarrhythmias. We investigated the early temporal sequence and reversibility of electrical remodeling in a rabbit complete heart block model subjected to bradycardic ventricular pacing for either 2 or 8 days, with a third group of animals undergoing 8 days of bradycardic pacing followed by 8 days of physiological-rate pacing. At specified time points after complete heart block induction and pacing initiation, steady-state QT interval measurements and variability as well as dynamic QT interval adaptation to abrupt heart rate acceleration were assessed in the absence and presence of isoproterenol. Rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier repolarizing K(+) tail current densities were evaluated using whole cell patch clamp in isolated right ventricular myocytes. Steady-state QT interval prolongation at both 2 and 8 days was associated with moderate I(Kr) reduction. I(Ks) downregulation was apparent by day 2 but more profound at day 8. Dynamic QT interval adaptation was impaired under baseline conditions at day 8 but only during isoproterenol administration at day 2. Both in vivo and cellular manifestations of remodeling reverted toward control values after 8 days of physiological-rate pacing. In conclusion, in this bradycardic model, I(Ks) downregulation 1) proceeds more gradually but more extensively than that of I(Kr) and 2) is most prominently associated with impaired dynamic QT interval adaptation to heart rate acceleration. Isoproterenol blunts the dynamic QT interval response in animals with partially downregulated I(Ks), consistent with stress-related phenomena in known I(Ks)-impaired states. Relative early sparing of I(Ks) could explain the delay in the onset of lethal tachyarrhythmia predisposition in bradycardic electrical remodeling. Reversibility of remodeling supports the potential utility of preventive pacing intervention soon after bradycardia onset.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…RV myocytes were isolated as described elsewhere (23). Briefly, the excised heart was retrogradely perfused for 10 min with nominally Ca 2ϩ free HEPES-buffered saline (HBS).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

Suto

Zhu²,

Chan³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

Comtois

Burstein

Nattel

2013

Electrical Diseases of the Heart

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The fundamental mechanisms underlying fi brillation have long been debated. The classical notion of multiple circuit reentry has been challenged by recent ideas suggesting that in some cases a single high-frequency rotor or even a rapidly-fi ring focus can underlie fi brillation that can cause wave breakup and fi brillation. There is increasing awareness that arrhythmias do not usually begin in perfectly normal tissue, but require changes in tissue structure or function that constitute the arrhythmic substrate. In this chapter, atrial and ventricular changes (including alterations in ion channel function, intercellular coupling, and fi brosis) playing a role in fi brillation are reviewed. We focus particularly on ischemic substrates, congestive heart failure remodeling, genetic factors, neuroregulatory determinants, and arrhythmic remodeling. Atrial (AF) and ventricular (VF) fi brillation-substrates have many features in common but also a number of important speci fi c differences. Consideration of these mechanistic determinants will lead to improved understanding of the pathophysiology of AF and VF, and ultimately to improve arrhythmia-speci fi c therapeutic approaches.

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Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

Burstein¹,

Comtois²,

Nattel³

Electrical Diseases of the Heart

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Ventricular rate determines early bradycardic electrical remodeling

Cited by 9 publications

References 32 publications

I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

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Ventricular rate determines early bradycardic electrical remodeling

Cited by 9 publications

References 32 publications

IKr and IKs remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

IKr and IKs remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

Comparisons of Substrates Responsible for Atrial Versus Ventricular Fibrillation

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I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits

I_Kr and I_Ks remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits