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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of VF.We also suggest that memory effects are responsible for the observed complexity dynamics.In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels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 In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels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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Current-voltage dependency for the  current in our model.The experimental data is from [16].
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pcbi-1003891-g001: Current-voltage dependency for the current in our model.The experimental data is from [16].

Mentions: We developed our model of the current based on the results of in vitro experiments [16]. Figure 1 shows measured current-voltage dependencies of for two different extracellular potassium concentrations. We fitted these data using functions with a power dependency on concentration and exponential functions of voltage, similar to functions used in [19], [20] for . Our expression for human was:(3)where is in mM, is transmembrane voltage measured in mV, and is the Nernst potential for potassium also in mV. Our function reproduces well the current-voltage dependency in a range between and mV. We also see some small deviations for lower and higher values of voltage, which, however, should not be essential as they are outside the important physiological range.


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)

Current-voltage dependency for the  current in our model.The experimental data is from [16].
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003891-g001: Current-voltage dependency for the current in our model.The experimental data is from [16].
Mentions: We developed our model of the current based on the results of in vitro experiments [16]. Figure 1 shows measured current-voltage dependencies of for two different extracellular potassium concentrations. We fitted these data using functions with a power dependency on concentration and exponential functions of voltage, similar to functions used in [19], [20] for . Our expression for human was:(3)where is in mM, is transmembrane voltage measured in mV, and is the Nernst potential for potassium also in mV. Our function reproduces well the current-voltage dependency in a range between and mV. We also see some small deviations for lower and higher values of voltage, which, however, should not be essential as they are outside the important physiological range.

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