Action potential duration restitution and ventricular fibrillation due to rapid focal excitation

2002 ◽  
Vol 282 (5) ◽  
pp. H1915-H1923 ◽  
Author(s):  
Moshe Swissa ◽  
Zhilin Qu ◽  
Toshihiko Ohara ◽  
Moon-Hyoung Lee ◽  
Shien-Fong Lin ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Tissue ◽  
Diacetyl Monoxime ◽  
Focal Excitation ◽  
Mean Cycle ◽  
Rapid Activation ◽  
Action Potential Duration Restitution ◽  
Wave Break

The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 μg) into normal isolated perfused swine right ventricles (RVs) stained with 4-{β-[2-(di- n-butylamino)-6-naphthyl]vinyl}pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 ± 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 ± 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10–20 mM, n = 6), bretylium (10–20 μg/ml, n = 3), and verapamil (2–4 μg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the “aconitine” site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.

Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue

2001 ◽  
Vol 280 (2) ◽  
pp. H535-H545 ◽  
Author(s):  
Fagen Xie ◽  
Zhilin Qu ◽  
Alan Garfinkel ◽  
James N. Weiss
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Tissue ◽  
Potential Model ◽  
Dynamic Instability ◽  
Spatial Scales ◽  
Cardiac Cells ◽  
Dynamic Factors ◽  
Cardiac Model ◽  
Wave Break

Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca2+ current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.

scholarly journals Intramural optical mapping of Vm and Cai2+ during long-duration ventricular fibrillation in canine hearts

2012 ◽  
Vol 302 (6) ◽  
pp. H1294-H1305 ◽  
Author(s):  
Wei Kong ◽  
Raymond E. Ideker ◽  
Vladimir G. Fast
Keyword(s):  
Ventricular Fibrillation ◽  
Action Potential ◽  
Short Duration ◽  
Action Potential Duration ◽  
Cycle Length ◽  
The Other ◽  
Membrane Voltage ◽  
Long Duration ◽  
Intracellular Ca ◽  
Rapid Pacing

Intramural gradients of intracellular Ca2+ (Cai2+) Cai2+ handling, Cai2+ oscillations, and Cai2+ transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Cai2+ handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Cai2+ handling contribute to LDVF, we measured membrane voltage ( Vm) and Cai2+ during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, Vm and Cai2+ progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed Vm upstrokes during pacing and LDVF. In conclusion, the fact that Vm upstrokes always preceded CaTs indicates that spontaneous Cai2+ oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong Vm-Cai2+ desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Cai2+ handling and may potentially contribute to LDVF maintenance.

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