Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.
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 In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels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.
Department of Physics and Astronomy, Ghent University, Ghent, Belgium.
Ivan V
IV
Kazbanov
INSIGNEO Institute for In-Silico Medicine, University of Sheffield, Sheffield, United Kingdom; Department of Computer Science, University of Sheffield, Sheffield, United Kingdom.
Richard H
RH
Clayton
Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; Department of Engineering Science, University of Auckland, Auckland, New Zealand.
Martyn P
MP
Nash
Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
Chris P
CP
Bradley
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
David J
DJ
Paterson
Departments of Cardiology and Cardiothoracic Surgery, University College Hospital, London, United Kingdom.
Martin P
MP
Hayward
Departments of Cardiology and Cardiothoracic Surgery, University College Hospital, London, United Kingdom.
Peter
P
Taggart
Department of Physics and Astronomy, Ghent University, Ghent, Belgium; Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russia.
Alexander V
AV
Panfilov
D003198:Computer Simulation; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D006947:Hyperkalemia; D000860:Hypoxia; D021621:Imaging, Three-Dimensional; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D014693:Ventricular Fibrillation / Q000473:pathology / Q000503:physiopathology*