| 1. |
- Almqvist, Joachim E, 1980, et al.
(författare)
-
Modeling the Effect of Kv1.5 Block on the Canine Action Potential
- 2010
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:9, s. 2726-2736
-
Tidskriftsartikel (refereegranskat)abstract
- A wide range of ion channels have been considered as potential targets for pharmacological treatment of atrial fibrillation. The Kv1.5 channel, carrying the IKur current, has received special attention because it contributes to repolarization in the atria but is absent or weakly expressed in ventricular tissue. The dog serves as an important animal model for electrophysiological studies of the heart and mathematical models of the canine atrial action potential (CAAP) have been developed to study the interplay between ionic currents. To enable more-realistic studies on the effects of Kv1.5 blockers on the CAAP in silico, two continuous-time Markov models of the guarded receptor type were formulated for Kv1.5 and subsequently inserted into the Ramirez-Nattel-Courtemanche model of the CAAP. The main findings were: 1), time- and state-dependent Markov models of open-channel Kv1.5 block gave significantly different results compared to a time- and state-independent model with a downscaled conductance; 2), the outcome of Kv1.5 block on the macroscopic system variable APD90 was dependent on the precise mechanism of block; and 3), open-channel block produced a reverse use-dependent prolongation of APD90. This study suggests that more-complex ion-channel models are a prerequisite for quantitative modeling of drug effects.
|
|
| 2. |
- Cardone-Noott, Louie, et al.
(författare)
-
A Computational Investigation into the Effect of Infarction on Clinical Human Electrophysiology Biomarkers
- 2014
-
Ingår i: Proceedings of the 41st Computing in Cardiology Conference, CinC 2014, Cambridge, United States, 7-10 September 2014. - 2325-8861. ; 41, s. 673-676
-
Konferensbidrag (refereegranskat)abstract
- The electrocardiogram (ECG) is often used to diag-nose myocardial infarction, but sensitivity and specificityare low. Here we present a computational framework forsolving the bidomain equations over an image-based hu-man geometry and simulating the 12 lead ECG. First, wedemonstrate this approach by evaluating a population ofeight models with varying distributions of local action po-tential duration, and report that only the model with apico-basal and inter-ventricular heterogeneities produces con-cordant T waves. Second, we simulate the effects of anold anterior infarct, which causes a reduction in T waveamplitude and width. Our methodology can contribute tothe understanding of ECG alterations under challengingconditions for clinical diagnosis.
|
|
| 3. |
- Wallman, Mikael, 1979, et al.
(författare)
-
Probabilistic Computational Assessment of Arrhythmic Risk in Post-Myocardial Infarction Human Ventricles
- 2014
-
Ingår i: In proceedings of Heart Rhythm 35th Annual Scientific Session.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Both electrophysiological and structural heterogeneities promote lethal ventricular tachyarrhythmias (VT) by favoring the establishment of reentry. However their relative contribution to arrhythmic risk after myocardial infarction (MI) remains unknown. Our aim is to quantify the associated risk from scar extent and repolarization gradients in the post-MI human ventricles.Methods: In silico investigations were performed in a personalized model of the human ventricles including fiber orientation post-MI scars and human membrane dynamics. Scars consisted of a non-conductive core zone and a border zone with heterogeneous conduction velocity allowing formation of slow conductive channels. Arrhythmic risk was quantified as the percentage of VT initiations following ectopic activation in the border zone. Over 4000 scenarios comprising >2M simulations were considered by varying scar structure under different transmural apex-base and left-to-right repolarization gradients.Results: VT was inducible in 3.27% of studied scar structures (Fig A). Successful VT initiations consistently occurred from ectopic locations close to the resulting reentrant circuit (3.65±4mm). Steep repolarization gradients increased arrhythmic risk by 15% on average with transmural gradients having the largest impact accentuating VT risk by 23% (Fig B).Conclusions: Steep repolarization dispersion potentiates the arrhythmogenic substrate in VT-inducible scars by promoting conduction block and reentry. These results support the role of repolarization dispersion in the onset of VT and may have important implications for risk stratification of post-MI patients.
|
|
