AI Article Synopsis
- Short-QT-syndrome type 1 (SQT1) is a heart condition caused by a genetic change that affects how the heart's electrical system works, leading to a higher risk of serious heart problems.
- In a study with rabbits that have SQT1, researchers found that giving them a substance called L-Carnitine helped lengthen the time it takes for the heart to reset after beating, which is a good thing for heart health.
- The study suggests that L-Carnitine works by improving the way certain electrical currents in the heart function, which might help people with this condition in the future.
Article Abstract
Aims: Short QT syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in human-ether-a-go-go (HERG) underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmacotherapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-short QT syndrome (SQTS) has been observed and rescued by carnitine supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS.
Methods And Results: Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo electrocardiograms (ECGs), ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. Two-dimensional computer simulations were performed to assess re-entry-based ventricular tachycardia-inducibility. L-Carnitine/C16-Carnitine prolonged QT-intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr changes as the main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D simulations revealed increased sustained re-entry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes.
Conclusion: L-Carnitine/C16-Carnitine prolong/normalize QT and whole-heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as a potential future QT-normalizing, anti-arrhythmic therapy in SQT1.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535723 | PMC |
| http://dx.doi.org/10.1093/cvr/cvae149 | DOI Listing |
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Article Synopsis
- Short-QT-syndrome type 1 (SQT1) is a heart condition caused by a genetic change that affects how the heart's electrical system works, leading to a higher risk of serious heart problems.
- In a study with rabbits that have SQT1, researchers found that giving them a substance called L-Carnitine helped lengthen the time it takes for the heart to reset after beating, which is a good thing for heart health.
- The study suggests that L-Carnitine works by improving the way certain electrical currents in the heart function, which might help people with this condition in the future.
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