Effects of Microgravity on Action Potential Wave Propagation in Rat Transmural Ventricle Tissue

Xiangyun Bai1, Kuanquan Wang1, Qince Li1, Cunjin Luo2, Yacong Li1, Henggui Zhang3
1School of Computer Science and Technology, Harbin Institute of Technology, 2Key Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China, 3Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester, UK School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.

Abstract

Aims: Experiments mimicking microgravity condition such as rat tail suspension have multiple effects on cardiac electrophysiology, including altering dynamics of several membrane currents and the expression of connexin 43. These electrophysiological changes result in heterogeneous variations of action potential duration (APD) in the endocardial and epicardial myocytes, which could be pro-arrhythmic. This study aimed to identify the predominate factors affecting action potential wave propagation in microgravity condition.

Methods: Based on the experimental data of rats with 2-weeks (short term) and 4-weeks (long term) tail suspension, the effects of microgravity on action potential were simulated by decreasing ICaL and increasing INaK based on biophysical detailed endocardial and epicardial models. Additionally, an one-dimensional (1D) model was constructed by considering the increasing of connexin 43 to study the electrocardiogram (ECG), transmural conduction of excitation waves and temporal vulnerability to unidirectional conduction block under microgravity condition.

Results: ICaL and INaK changes have similar effect in reducing APD90 under short term condition, while the inhibition of ICaL is the main factor in reducing APD90 under long term condition. The simulated pseudo-ECG in both conditions showed a shortened QT interval and depressed of ST phase and T wave as experimental observations. Increased expression of connexin 43 in microgravity condition resulted in a mild increase in conduction velocity. Meanwhile, the vulnerable window in 1D ventricle strand reduced in microgravity condition. Compared with short term microgravity condition, all these changes were more prominent in the long term experiments.

Conclusion: ICaL variation plays a dominant role in regulating APD90 in the long term microgravity conditions, suggesting it might be a potential therapeutic target for the long term microgravity induced short QT syndrome. These results also partially explained that weightlessness reduces the occurrence of arrhythmias, but enhances the fatalness if arrhythmias did occur during spaceflight.