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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of VF.We also suggest that memory effects are responsible for the observed complexity dynamics.In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels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 In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels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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Two examples of how hypoxia and hyperkalemia evolve during course of ischemia.Pink: clinical data on the dominant frequency, averaged over 1 s window with standard deviation. Blue: smoothed curve used for the fitting. Red: extracellular potassium concentration. Green: fraction of activated  channels. The left vertical axis corresponds both to the extracellular potassium in mM and the dominant frequency in Hz. The right axis corresponds to the fraction of activated channels, measured in percents.
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pcbi-1003891-g007: Two examples of how hypoxia and hyperkalemia evolve during course of ischemia.Pink: clinical data on the dominant frequency, averaged over 1 s window with standard deviation. Blue: smoothed curve used for the fitting. Red: extracellular potassium concentration. Green: fraction of activated channels. The left vertical axis corresponds both to the extracellular potassium in mM and the dominant frequency in Hz. The right axis corresponds to the fraction of activated channels, measured in percents.

Mentions: We also estimated how hypoxia and hyperkalemia change in the course of ischemia. This problem of fitting does not have a unique solution because the period of fibrillation depends on two parameters, while we have only one period dependency for each patient. To account for that we assumed that the dependencies of and are monotonic with time, and these values can never decrease during ischemia. Then we wrote the relation between the rate of change of these values:(5)where is the period of fibrillation over time (from the clinical results) and is the dependency of VF period on the ischemia components, obtained from Figure 5. Our goal was to determine the patient specific functions and , based on known , and boundary conditions from Table 2. To solve (5) we needed to impose an additional constraint on our functions. Thus we assume that(6)where and are the values we fitted for point B. This constraint ensured the values of hypoxia and hyperkalemia tended to reach those values at point B. The results we obtained using this approach for two patients are shown in Figure 7. The rest of the results for all 10 patients are available in Figures S1–S10. We see that we can fit the clinical data with smooth monotonic functions using our approach. However, as our constraint (6) cannot be justified from biological background, these fits can be considered as a conjecture rather than established results.


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)

Two examples of how hypoxia and hyperkalemia evolve during course of ischemia.Pink: clinical data on the dominant frequency, averaged over 1 s window with standard deviation. Blue: smoothed curve used for the fitting. Red: extracellular potassium concentration. Green: fraction of activated  channels. The left vertical axis corresponds both to the extracellular potassium in mM and the dominant frequency in Hz. The right axis corresponds to the fraction of activated channels, measured in percents.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003891-g007: Two examples of how hypoxia and hyperkalemia evolve during course of ischemia.Pink: clinical data on the dominant frequency, averaged over 1 s window with standard deviation. Blue: smoothed curve used for the fitting. Red: extracellular potassium concentration. Green: fraction of activated channels. The left vertical axis corresponds both to the extracellular potassium in mM and the dominant frequency in Hz. The right axis corresponds to the fraction of activated channels, measured in percents.
Mentions: We also estimated how hypoxia and hyperkalemia change in the course of ischemia. This problem of fitting does not have a unique solution because the period of fibrillation depends on two parameters, while we have only one period dependency for each patient. To account for that we assumed that the dependencies of and are monotonic with time, and these values can never decrease during ischemia. Then we wrote the relation between the rate of change of these values:(5)where is the period of fibrillation over time (from the clinical results) and is the dependency of VF period on the ischemia components, obtained from Figure 5. Our goal was to determine the patient specific functions and , based on known , and boundary conditions from Table 2. To solve (5) we needed to impose an additional constraint on our functions. Thus we assume that(6)where and are the values we fitted for point B. This constraint ensured the values of hypoxia and hyperkalemia tended to reach those values at point B. The results we obtained using this approach for two patients are shown in Figure 7. The rest of the results for all 10 patients are available in Figures S1–S10. We see that we can fit the clinical data with smooth monotonic functions using our approach. However, as our constraint (6) cannot be justified from biological background, these fits can be considered as a conjecture rather than established results.

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