Metabolic treatment of an electrical disease? Beneficial APD/QT prolongation by L-Carnitine in transgenic SQT1 rabbit models
| Autor: | T Hornyik, I Bodi, K Michaelides, L Mettke, S Perez-Feliz, I El-Battrawy, M Brunner, C Bode, K Odening |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | European Heart Journal. 42 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehab724.3212 |
| Popis: | Background Short-QT syndrome 1 (SQT1) is a genetic cardiac channelopathy caused by gain-of-function mutations (KCNH2-N588K) in HERG/IKr, that leads to shortened QT-interval, increased risk for arrhythmias and sudden cardiac death (SCD). An acquired form of SQTS has been described in patients with primary (genetic) carnitine-deficiency, indicating that carnitine might affect cardiac repolarization. Purpose We aimed to investigate potential beneficial (APD/QT-prolonging) effect of L-Carnitine in (genetic) SQTS using transgenic SQT1 rabbits that mimic the human disease phenotype. Methods Effects of L-carnitine on cardiac repolarisation were assessed in adult wildtype (WT) and transgenic SQT1 rabbits (KCNH2-N588K) using in vivo ECG and ex vivo Langendorff-perfused whole-heart or isolated ventricular cardiomyocyte action potential (AP) recordings. Effects on ion currents were assessed by whole-cell patch-clamping. Results In vivo, the heart-rate corrected QT index (QTi) was prolonged significantly by L-carnitine both in WT (QTi, baseline 102.7%±4.9 vs. L-carnitine 106.9%±6.2, p Conclusion L-carnitine prolongs/normalizes QT and APD in transgenic SQT1 rabbits by decreasing the pathologically increased IKr-steady and also IKs-steady and may therefore serve as potential future anti-arrhythmic therapy in SQTS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Research Foundation (DFG) |
| Databáze: | OpenAIRE |
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