Ventricular Fibrillation in the Human Heart. Why is it different from Fibrillation in the Dog and Pig Heart?

author: Kirsten ten Tusscher, Department of Theoretical Biology / Bioinformatics, Faculty of Biology, Utrecht University
published: Nov. 27, 2007,   recorded: October 2007,   views: 1948
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Sudden cardiac death is one of the major health problems in the industrialised world, leading to over 300,000 mortalities in the US alone annually. In most cases, it is caused by a cardiac arrhythmia called ventricular fibrillation (VF). Under normal conditions, the coordinated contraction of the heart leads to an effective pumping of blood through the body. In contrast, during fibrillation coordination of contraction is completely lost, rendering the heart incapable of pumping around blood. Despite the huge socio-economical costs of VF and decades of research its causes and mechanisms still remainpoorly understood. In experimental studies into the mechanisms of VF, pig and dog hearts are considered the best model systems for the human heart given their comparable size. In such studies it is found that fibrillation is caused by highly disorganised electrical wave patterns consisting of 50 or more rotating spiral waves. It has been assumed that a similar organisation underlieshuman VF. However, recent clinical studies suggest that fibrillation inthe human heart may have a far more simple organisation.Modelling studies have played an important role and are playing an increasingly important role in cardiac arrhythmia research from the single ion channel to the whole heart level. However, on the whole heart level, most modelling studies thus far have used phenomenological models or small heart animal models to obtain qualitative insights in VF mechanisms and patterns. Instead, we use a detailed model of the human ventricles, to quantitatively study human VF and why it might be different from VF in the pig and dog heart. We indeed find that human VF has a significantly simpler organisation than VF in the pig and dog heart, with wave patterns consisting of around 10 spiral waves only. We then study the dependence of VF wave pattern complexity on various major parameters of our model (excitability, anisotropy, action potential duration (APD) restitution slope, minimum APD). We find that VF wave pattern complexity is most strongly dependent on minimum APD, a factor that is found to differ between human and pig and dog hearts. We thus propose that differences in minimum action potential duration cause the differences in wave pattern complexity during VF in the human and pig and dog hearts. Both the simpler spatial organisation of human VF and it's suggested cause may have important implications for treating and preventing this dangerous arrhythmia in humans.

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