Session P94.5

Quantifying the Effects of Ischaemia on Electrophysiology and the ST Segment of the ECG in Human Virtual Ventricular Cells and Tissues

AP Benson*, EK Hodgson, O Bernus, AV Holden

University of Leeds
Leeds, UK

Myocardial ischaemia is caused by reduced coronary blood flow and can lead to critical impairment of both the electrical and mechanical functioning of the heart. In Europe, ischaemic heart disease accounts for nearly two million deaths per year. Computer simulations help overcome some of the limitations of clinical studies and are able to dissect out and examine the relationship between individual electrophysiological parameters. We used the human model of Ten Tusscher & Panfilov (2006, Am J Physiol 291;1088). The cellular electrophysiological components of ischaemia were incorporated as in Shaw & Rudy (1997, Cardiovasc Res 35;124), but we reduced the maximal conductance of the ATP-sensitive potassium current to 20% of the original value and set extracellular potassium during hyperkalaemia to 10 mM to ensure realistic changes in action potential duration (APD) and resting membrane potential (RMP). These cell models were incorporated into a 15 mm heterogeneous one-dimensional strand model of the human left ventricular free wall (Benson et al., 2007, Chaos 17;015105). In the single human ventricular myocyte models, hyperkalaemia causes the greatest depolarisation of RMP, resulting in relatively more sodium channels remaining in the inactivated state and a concomitant reduction in membrane excitability. The anoxic component of ischaemia causes the greatest shortening of APD, and is the greatest contributor to abnormal repolarisation patterns. In the human strand tissue model, sub-endocardial ischaemia causes a depression in the ST segment and can cause inverted T waves. The amount of depression shows a biphasic relationship to the extent of the ischemic region. This depression is due to two components: firstly, spatial gradients in APD that can reverse the pattern of repolarisation; and secondly, gradients that exist between RMP in the normal and ischaemic tissues. However, unlike Aslanidi et al. (2005, J Theor Biol 237;369) who identified hyperkalaemia as the main contributor to ST segment depression using a guinea pig model, we found in the human model that the main contributors are both anoxia and hyperkalaemia. In conclusion, we have developed an electrophysiological model of ischaemia in human ventricular myocardium. We performed the first mechanistic investigation of ST segment depression in such a model and highlighted key differences with previous computational studies based on animal models.

(Abstract Control Number: 19)