Abstract

Hypothermia has a profound impact on the electrophysiological mechanisms of the heart. Experimental investigations provide a better understanding of electrophysiological alterations associated with cooling. However, there is a lack of computer models suitable for simulating the effects of hypothermia in cardio-electrophysiology. In this work, we propose a model that describes the cooling-induced electrophysiological alterations in ventricular tissue in a temperature range from 27°C to 37°C. To model the electrophysiological conditions in a 3D left ventricular tissue block it was essential to consider the following anatomical and physiological parameters in the model: the different cell types (endocardial, M, epicardial), the heterogeneous conductivities in longitudinal, transversal and transmural direction depending on the prevailing temperature, the distinct fiber orientations and the transmural repolarization sequences. Cooling-induced alterations on the morphology of the action potential (AP) of single myocardial cells thereby are described by an extension of the selected Bueno-Orovio model for human ventricular tissue using Q10 temperature coefficients. To evaluate alterations on tissue level, the corresponding pseudo electrocardiogram (pECG) was calculated. Simulations show that cooling-induced AP and pECG-related parameters, i.e. AP duration, morphology of the notch of epicardial AP, maximum AP upstroke velocity, AP rise time, QT interval, QRS duration and J wave formation are in good accordance with literature and our experimental data. The proposed model enables us to further enhance our knowledge of cooling-induced electrophysiological alterations from cellular to tissue level in the heart and may help to better understand electrophysiological mechanisms, e.g. in arrhythmias, during hypothermia.

Highlights

  • Hypothermia has a relevant impact on physiological regulatory mechanisms in the pulmonary, neurologic, hemostatic and cardiovascular system [1]

  • Utilizing this technique at hypothermic conditions led to the following primary findings: On a cellular level hypothermia induces a prolongation of the action potential duration (APD) of myocardial cells, resulting in a change of the the repolarization wave (T-wave) morphology and a prolongation of the QT interval in the ECG

  • Hypothermia has a significant effect on the electrophysiology of the heart

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Summary

Introduction

Hypothermia has a relevant impact on physiological regulatory mechanisms in the pulmonary, neurologic, hemostatic and cardiovascular system [1]. Deflecting the attention on the heart, hypothermia-induced electrophysiological changes can be observed through morphologic variances in the electrocardiogram (ECG) recording [5,6] These variances originate at the cellular level and are primarily caused by alterations in ion channel dynamics. Various experiments in mammalian ventricular wedge models have advanced our knowledge on the relationship between the effects of this electric heterogeneity on transmembrane potential in distinct cell types and its contribution to the morphology of registered ECG signals by simultaneous recording of transmembrane APs and pseudo-ECG (pECG) Utilizing this technique at hypothermic conditions led to the following primary findings: On a cellular level hypothermia induces a prolongation of the action potential duration (APD) of myocardial cells, resulting in a change of the T-wave morphology and a prolongation of the QT interval in the ECG. On a cellular basis the notch is caused by a transmural voltage gradient, originating from the presence of a notch in phase 1 of the AP (between maximum deflection and plateau-phase) of epicardial cells [11,12]

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