Differences in extent of mechano-induced QT-changes in SQTS, WT and LQTS rabbit models

Abstract Background Electro-mechanical (EMC) and mechano-electrical coupling (MEC) are essential for normal cardiac function. Alterations in these can result increased arrhythmia formation. In “electrical” diseases, long-QT short-QT syndrome, regional mechanical function is altered via EMC. Purpose this study, we aimed to investigate how acute changes mechanics may impact on electrical diseases. Methods To determine preload QT duration, adult rabbits of both sexes were given a 6ml/kg BW bolus 0.9% NaCl IV 12-lead-ECGs assessed first wildtype (WT) acquired drug-induced (E4031 block IKr) LQT2 (“aLQT2”) rabbits, second step transgenic type 1 (“SQT1”, KCNH2-N588K) WT littermate control (“WT-LMC”). Results At baseline, aLQT2 demonstrated markedly prolonged heart-rate corrected QTc duration compared (p<0.0001; n=13), with QT-dispersion (QTMax-Min [ms], 21.4±5.7 vs. 25.8±5.8; p=0.003; n=13) short-term variability (STVQT 3.5±1.0 5.3±1.7; p=0.02; markers temporal heterogeneity repolarization, respectively. SQT1 (n=8) shorter WT-LMC (n=10; p=0.04), no differences STVQT between the two groups. Increased acutely all groups (despite slight increase by an average 25 beats/min): [ms] 171.6±11.6 213.3±20.3 (p<0.0001) 208.9±19.6 271.0±37.5 n=13 each), 171.3±4.8 199.2±5.4 n=10) 156.0±4.7 177.3±3.5 (p=0.0004; n=8). Importantly, extent mechano-induced differed among genotypes, less pronounced prolongation (delta 21.2±3.4 27.9±2.8 p=0.15)), more 41.6±14.9 62.1±32.1; p=0.006; each). Moreover, was significantly upon global change only aLQTS 25.8±5.5 32.7±12.3; p=0.03; n=13). Conclusion Acute MEC SQT1, rabbits. The changes, however, depends underlying least shortest QTc, most longest QTc. effects as well dispersion indicate that play additional role LQTS-related arrhythmogenesis. FUNDunding Acknowledgement Type funding sources: Foundation. Main source(s): German Research Foundation (DFG) andSwiss National Science (SNF)