Změny spontánní aktivity derivovaných kardiomyocytů s variantou Y4734C-RYR2 za vybraných arytmogenních podmínek

Title in English Changes of spontaneous activity of derived cardiomyocytes carrying a variant Y4734-RYR2 in selected proarrhythmic conditions


Year of publication 2023
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Description Introduction: Idiopathic ventricular fibrillation (iKF) is a life-threatening condition even in young adults. Variants in the genes encoding the structure of cardiac ion channels can be detected in some patients with this condition. This was also the case in our proband with iKF, in whom a previously unknown variant Y4734C in the ryanodine receptor type 2 (RYR2) gene was discovered. Commonly, pathological variants in RYR2 are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This is also the case in the sister of a proband with the same variant in RYR2, but the proband does not show signs of CPVT. As the patient developed iKF from unknown causes, we investigated the spontaneous activity of patient-specific cardiomyocyte-derived human induced pluripotent stem cell (hiPSC-CM) under selected arrhythmogenic conditions. Materials and Methods: hiPSC-CMs from a proband with iKF (IF), a proband's sister with CPVT (CPVT), a proband's nephew as a healthy related control (WT), and a healthy unrelated control (M67) were used for the measurements.Their spontaneous activity was detected by the microelectrode array method in control solution (Tyrode's solution 5 mM K+, 37°C; abbreviated Tyr 5 mM K+), in solution with reduced potassium concentration (Tyrode's solution 3 mM K+, 37°C; abbreviated Tyr 3 mM K+), after addition of isoprenaline (ISO) and at elevated temperature (40°C). Cycle length (CL) and its short-term variability (STVCL) were evaluated. The data obtained did not have a normal distribution; therefore, means are reported as median and interquartile range (IQR) and non-parametric statistical tests were used. RESULTS: CL values were not statistically significantly different between the hiPSC-CM groups tested. Statistically significant CL shortening was observed for IF between Tyr 3 mM K+ and Tyr 3 mM K+ + ISO + 40 °C and for M67 between Tyr 5 mM K+ and Tyr 3 mM K+ + ISO. STVCL was statistically significantly different only between M67 and IF at Tyr 3 mM K+ + ISO + 40°C. No statistically significant difference in STVCL was observed between other groups or within groups under different conditions. Conclusion: pilot data showed that changes in CL were not significant between groups and often not significant within groups. Of particular significance is the finding of significantly higher STVCL in IF after the accumulation of three potentially pro-arrhythmogenic stimuli relevant to clinical practice, i.e. hypocalcemia, ß-adrenergic stimulation and fever.
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