scholarly journals Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure

1999 ◽  
Vol 277 (1) ◽  
pp. H80-H91 ◽  
Author(s):  
H. Bradley Nuss ◽  
Stefan Kääb ◽  
David A. Kass ◽  
Gordon F. Tomaselli ◽  
Eduardo Marbán
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ventricular Arrhythmias ◽  
Torsade De Pointes ◽  
Resting Potential ◽  
Unexpected Finding ◽  
Early Afterdepolarizations ◽  
Ventricular Cells ◽  
High Incidence ◽  
Delayed Afterdepolarizations

The high incidence of sudden death in heart failure may reflect an increased propensity to abnormal repolarization and long Q-T interval-related arrhythmias. If so, cells from failing hearts would logically be expected to exhibit a heightened susceptibility to early afterdepolarizations (EAD). We found that midmyocardial ventricular cells isolated from dogs with pacing-induced heart failure exhibited an increased action potential duration and many more EAD than cells from nonpaced controls; this was the case both under basal conditions ( P < 0.01) and after lowering external K+concentration ([K+]o) to 2 mM and exposing cells to cesium (3 mM; P < 0.05). An unexpected finding was the occurrence of spontaneous depolarizations (SD, >5 mV) from the resting potential that were not coupled to prior action potentials. These SD were observed in 20% of failing cells ( n = 5 of 25) under basal ionic conditions but in none of the normal cells ( n = 0 of 27, P < 0.05). The net inward current that underlies SD is not triggered by Ca2+ oscillations and thus differs fundamentally from the currents that underlie delayed afterdepolarizations. We conclude that cardiomyopathic canine ventricular cells are intrinsically predisposed to EAD and SD. Because EAD have been linked to the pathogenesis of torsade de pointes, our results support the hypothesis that sudden death in heart failure often arises from abnormalities of repolarization. The frequent occurrence of SD points to a novel cellular mechanism for abnormal automaticity in heart failure.

scholarly journals Ventricular Arrhythmias Underlie Sudden Death in Rats With Heart Failure and Preserved Ejection Fraction

2018 ◽  
Vol 11 (8) ◽  
Author(s):  
Jae Hyung Cho ◽  
Rui Zhang ◽  
Stephan Aynaszyan ◽  
Kevin Holm ◽  
Joshua I. Goldhaber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Ventricular Arrhythmias ◽  
Preserved Ejection Fraction

Ambulatory Ventricular Arrhythmias in Patients With Heart Failure Do Not Specifically Predict an Increased Risk of Sudden Death

Circulation ◽  
2000 ◽  
Vol 101 (1) ◽  
pp. 40-46 ◽  
Author(s):  
John R. Teerlink ◽  
Muhammad Jalaluddin ◽  
Susan Anderson ◽  
Marrick L. Kukin ◽  
Eric J. Eichhorn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ventricular Arrhythmias ◽  
Increased Risk ◽  
Patients With Heart Failure

Inducible ventricular arrhythmias and sudden death during vasodilator therapy of severe heart failure

1988 ◽  
Vol 116 (6) ◽  
pp. 1447-1454 ◽  
Author(s):  
William G Stevenson ◽  
Lynne W Stevenson ◽  
James Weiss ◽  
Jan H Tillisch
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ventricular Arrhythmias ◽  
Severe Heart Failure ◽  
Vasodilator Therapy

scholarly journals The association between pro-arrhythmic agents and aortic stenosis in young adults: is it sufficient to clarify the sudden unexpected deaths?

2016 ◽  
Vol 27 (5) ◽  
pp. 929-935 ◽  
Author(s):  
Bojana Radnic ◽  
Nemanja Radojevic ◽  
Jelena Vucinic ◽  
Natasa Duborija-Kovacevic
Keyword(s):  
Young Adults ◽  
Sudden Death ◽  
Aortic Stenosis ◽  
Ventricular Arrhythmias ◽  
Young Patients ◽  
Electrolyte Imbalance ◽  
Unexpected Death ◽  
Congenital Aortic Stenosis ◽  
High Incidence ◽  
Toxic Concentrations

AbstractMost young patients with mild-to-moderate aortic stenosis show no symptoms, and sudden death appears only occasionally. We hypothesised that malignant ventricular arrhythmias could be responsible for the high incidence of sudden death in such patients. If multiple factors such as asymptomatic aortic stenosis in association with arrhythmia-provoking agents are involved, could it be sufficient to account for sudden unexpected death? In this study, eight cases of sudden death in young adults, with ages ranging from 22 to 36 years, who had never reported any symptoms that could be related to aortic stenosis, were investigated. Full autopsies were performed, and congenital aortic stenosis in all eight cases was confirmed. DNA testing for channelopathies was negative. Comprehensive toxicological analyses found an electrolyte imbalance, or non-toxic concentrations of amitriptyline, terfenadine, caffeine, and ethanol. Collectively, these results suggest that congenital asymptomatic aortic stenosis without cardiac hypertrophy in young adults is not sufficient to cause sudden death merely on its own; rather, an additional provoking factor is necessary. According to our findings, the provoking factor may be a state of physical or emotional stress, a state of electrolyte imbalance, or even taking a therapeutic dose of a particular drug.

scholarly journals Changes in Sinus Node Function in a Rabbit Model of Heart Failure With Ventricular Arrhythmias and Sudden Death

Circulation ◽  
2000 ◽  
Vol 101 (25) ◽  
pp. 2975-2980 ◽  
Author(s):  
Tobias Opthof ◽  
Ruben Coronel ◽  
Han M. E. Rademaker ◽  
Jessica T. Vermeulen ◽  
Francien J. G. Wilms-Schopman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Death ◽  
Ventricular Arrhythmias ◽  
Sinus Node ◽  
Rabbit Model

scholarly journals Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models

2021 ◽  
Vol 8 ◽  
Author(s):  
Gary Tse ◽  
Ka Hou Christien Li ◽  
Chloe Kwong Yee Cheung ◽  
Konstantinos P. Letsas ◽  
Aishwarya Bhardwaj ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Arrhythmias ◽  
Molecular Mechanisms ◽  
Clinical Findings ◽  
Excitation Wavelength ◽  
Early Afterdepolarizations ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Clinical Models ◽  
Delayed Afterdepolarizations

Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD–ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.

scholarly journals Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes

2020 ◽  
Vol 126 (7) ◽  
pp. 889-906 ◽  
Author(s):  
Kiarash Tazmini ◽  
Michael Frisk ◽  
Alexandre Lewalle ◽  
Martin Laasmaa ◽  
Stefano Morotti ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Atrial Myocytes ◽  
Early Afterdepolarizations ◽  
Membrane Hyperpolarization ◽  
Atrial Cells ◽  
Ventricular Cells ◽  
Rat Myocytes ◽  
Delayed Afterdepolarizations ◽  
T Tubules ◽  
A Current

Rationale: Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes. Objective: To investigate proarrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes. Methods and Results: Experiments were performed in isolated rat myocytes exposed to simulated hypokalemia conditions (reduction of extracellular [K + ] from 5.0 to 2.7 mmol/L) and supported by mathematical modeling studies. Ventricular cells subjected to hypokalemia exhibited Ca 2+ overload and increased generation of both spontaneous Ca 2+ waves and delayed afterdepolarizations. However, similar Ca 2+ -dependent spontaneous activity during hypokalemia was only observed in a minority of atrial cells that were observed to contain t-tubules. This effect was attributed to close functional pairing of the Na + -K + ATPase and Na + -Ca 2+ exchanger proteins within these structures, as reduction in Na + pump activity locally inhibited Ca 2+ extrusion. Ventricular myocytes and tubulated atrial myocytes additionally exhibited early afterdepolarizations during hypokalemia, associated with Ca 2+ overload. However, early afterdepolarizations also occurred in untubulated atrial cells, despite Ca 2+ quiescence. These phase-3 early afterdepolarizations were rather linked to reactivation of nonequilibrium Na + current, as they were rapidly blocked by tetrodotoxin. Na + current-driven early afterdepolarizations in untubulated atrial cells were enabled by membrane hyperpolarization during hypokalemia and short action potential configurations. Brief action potentials were in turn maintained by ultra-rapid K + current (I Kur ); a current which was found to be absent in tubulated atrial myocytes and ventricular myocytes. Conclusions: Distinct mechanisms underlie hypokalemia-induced arrhythmia in the ventricle and atrium but also vary between atrial myocytes depending on subcellular structure and electrophysiology.

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