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A new tool for the action potential repolarization dynamic analysis: Application to the discrimination of diabetic and control cells

Abstract : In CinC2015 we have shown that the dynamics of the action potential (AP) repolarization could be tracked throughout the stimulation course. Despite some valuable outcomes, the populations of interest (control, Ctrl, and streptozotocin-induced, STZ, diabetic mice) could not be significantly distinguished in term of dynamics because of the global extracted feature. In this study, the computation of new features for each repolarization percentage allows an accurate and meaningful characterization of the two groups leading to a significant classification. APs in isolated left ventricular cardiomyocytes obtained from Ctrl and STZ mice were measured by patch-clamp. The progressive changes in AP repolarization for individual cells were tested on a set of 100 consecutive excita-tions at 2Hz pacing rate. The corresponding repolariza-tions are stacked in a matrix decomposed with a new approach. Observations are modeled as a sum of vectors multiplied by specific polynomial functions. This approach is similar to the Singular Value Decomposition (SVD), but the corresponding scalars are replaced by these functions. Model unknowns are estimated by using an alternated least square algorithm. Finally, the mean of the polynomial first derivative is computed for each repolarization percentage as a representative feature. A Wilcoxon signed rank test (p<0.05) has been applied on the features from the two groups. We can observe a significant difference in the late repolarization phase (70%-95% repolarization), with a singular behavior in correspondence with the AP profile shoulder onset (80%). 1. Introduction The duration of the action potential (AP) in cardiomy-ocytes is an important variable controlling the electrical properties of the normal and pathological myocardium. Prolongation of the AP in myocytes may represent the basis for the increased risk of arrhythmia with diabetes [1], but the determinants of these abnormalities remain to be elucidated. We have shown in [2] that the diabetic condition is associated with alterations in the temporal dynamics of the AP profile in myocytes, a factor that may originate electrical instability. This assessment has been performed by using statistics computed over APs associated to isolated left ventricular myocytes obtained from control (Ctrl)and streptozotocin-induced (STZ) diabetic mice. In [3], these statistical properties (mean and variance) have been replaced by the analysis of the temporal dynamics of the repolarization phase. It has been shown that the two groups could be partly distinguished by introducing a new automatic analysis based on a transformation of each AP. The objective of this paper is not restricted to only fully distinguish the two groups but also to produce additional predictive information on the ionic currents involved in the observed differences. For instance, if the groups are significantly different at specific percentages of repolariza-tion, it implies that ionic currents active in these membrane potential ranges are affected by the hyperglycemic condition. To achieve this task, we introduced a new decomposition method, well adapted to the observation, based on the aforementioned AP transformation. It is shown that the proposed approach succeeded in distinguishing the electrical behavior of the two groups of cells, corroborating the impact of diabetes on repolarizing Kv currents. 2. Material A group of female C57Bl/6 mice between 3 and 4.4 months of age was studied in accordance with the Guide for Care and Use of Laboratory Animals; experiments were approved by the local animal care committee (IACUC). Hyperglycemia was induced by injecting animals with streptozotocin (Sigma, concentration 5 mg/L) for approximately one week. Blood glucose levels were measured 6-10 days after the last injection of STZ. Mice
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Contributor : Olivier Meste <>
Submitted on : Wednesday, October 19, 2016 - 5:57:19 PM
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  • HAL Id : hal-01384379, version 1



Olivier Meste, Marianna Meo, M Signore, M Rota. A new tool for the action potential repolarization dynamic analysis: Application to the discrimination of diabetic and control cells. Computing in Cardiology, Sep 2016, Vancouver, Canada. ⟨hal-01384379⟩



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