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Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.

Kazbanov IV, Clayton RH, Nash MP, Bradley CP, Paterson DJ, Hayward MP, Taggart P, Panfilov AV - PLoS Comput. Biol. (2014)

Bottom Line: A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF.We also suggest that memory effects are responsible for the observed complexity dynamics.In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Ghent University, Ghent, Belgium.

ABSTRACT
Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

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Change of DF over time for one patient (H066).Red denotes DF recorded with the heart perfused, blue denotes ischemia, and green reflow. The middle line shows mean DF, averaged over electrodes, and the top and the bottom lines show one standard deviation either side of the mean.
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pcbi-1003891-g006: Change of DF over time for one patient (H066).Red denotes DF recorded with the heart perfused, blue denotes ischemia, and green reflow. The middle line shows mean DF, averaged over electrodes, and the top and the bottom lines show one standard deviation either side of the mean.

Mentions: Our results allowed us to estimate the extent of hyperkalemia and hypoxia for each patient involved in the clinical study [13]. We used the dependency of how DF (1/period) changes throughout experimental VF for individual patients. One of these recordings is shown in Figure 6. The red region corresponds to normal perfusion of the heart, blue to global ischemia and the green to reperfusion. As one can see, DF gradually decreases during ischemia and then increases abruptly after reperfusion to an even higher level that it was initially.


Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.

Kazbanov IV, Clayton RH, Nash MP, Bradley CP, Paterson DJ, Hayward MP, Taggart P, Panfilov AV - PLoS Comput. Biol. (2014)

Change of DF over time for one patient (H066).Red denotes DF recorded with the heart perfused, blue denotes ischemia, and green reflow. The middle line shows mean DF, averaged over electrodes, and the top and the bottom lines show one standard deviation either side of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222598&req=5

pcbi-1003891-g006: Change of DF over time for one patient (H066).Red denotes DF recorded with the heart perfused, blue denotes ischemia, and green reflow. The middle line shows mean DF, averaged over electrodes, and the top and the bottom lines show one standard deviation either side of the mean.
Mentions: Our results allowed us to estimate the extent of hyperkalemia and hypoxia for each patient involved in the clinical study [13]. We used the dependency of how DF (1/period) changes throughout experimental VF for individual patients. One of these recordings is shown in Figure 6. The red region corresponds to normal perfusion of the heart, blue to global ischemia and the green to reperfusion. As one can see, DF gradually decreases during ischemia and then increases abruptly after reperfusion to an even higher level that it was initially.

Bottom Line: A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF.We also suggest that memory effects are responsible for the observed complexity dynamics.In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Ghent University, Ghent, Belgium.

ABSTRACT
Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

Show MeSH
Related in: MedlinePlus