Differences in extent of mechano-induced QT-changes in SQTS, WT and LQTS rabbit models
| Autor: | T Hornyik, K R Moss, Manfred Zehender, Katja E. Odening, N Alerni, Stefanie Perez-Feliz, Michael Brunner, S Nimani, Lucilla Giammarino, R Lewetag, L Matas, Gunnar Seemann |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | European Heart Journal. 42 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Background Electro-mechanical (EMC) and mechano-electrical coupling (MEC) are essential for normal cardiac function. Alterations in these can result in increased arrhythmia formation. In “electrical” cardiac diseases, long-QT and short-QT syndrome, regional mechanical function is altered via EMC. Purpose In this study, we aimed to investigate how acute changes in mechanics may impact on electrical function (MEC) in these diseases. Methods To determine how acute changes in preload impact on QT duration, adult rabbits of both sexes were given a 6ml/kg BW bolus of 0.9% NaCl IV and 12-lead-ECGs were assessed first in wildtype (WT) and acquired drug-induced (E4031 to block IKr) LQT2 (“aLQT2”) rabbits, and in a second step in transgenic short-QT type 1 (“SQT1”, KCNH2-N588K) and WT littermate control rabbits (“WT-LMC”). Results At baseline, aLQT2 rabbits demonstrated a markedly prolonged heart-rate corrected QTc duration compared to WT (p Increased preload acutely prolonged QT and heart-rate corrected QTc in all groups (despite a slight increase in heart-rate by an average of 25 beats/min): in WT [ms] 171.6±11.6 to 213.3±20.3 (p Conclusion Acute changes in mechanical function result in electrical changes via MEC in SQT1, WT and aLQT2 rabbits. The extent of these changes, however, depends on the underlying QTc duration, with the least pronounced QTc prolongation in SQT1 rabbits, with the shortest QTc, and the most pronounced QTc prolongation in aLQT2 rabbits, with the longest QTc. The most pronounced MEC effects on global QT duration as well as on regional QT dispersion in aLQT2 indicate that acute MEC effects may play an additional role in LQTS-related arrhythmogenesis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Research Foundation (DFG) andSwiss National Science Foundation (SNF) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|