Abstract 14720: Postpartum Hormones Oxytocin and Prolactin Alter Cardiac Repolarization in Transgenic Long-QT Type 2 Rabbits by Affecting IKs Current Densities and Ca2+ Cycling Protein Transcription
Introduction: Women with long-QT syndrome 2 (LQT2) are at increased risk for polymorphic VTs and sudden cardiac death - particularly during the postpartum. We hypothesize that postpartum hormones oxytocin (OXY) and prolactin (PRL) alter the arrhythmogenic risk in LQT2 by affecting cardiac repolarization.
Methods: Female transgenic LQT2 rabbits (10/group) treated with OXY (3U), PRL (4U), or NaCl (SHAM) for 2 weeks were ECG monitored to detect changes in QT/RR. Action potential duration (APD) was assessed in Langendorff-perfused hearts before and during acute hormone-perfusion (0.2ng/l - 200ng/l). qPCR (4/group) was performed to detect hormone effects on ion channel and Ca2+ cycling protein transcription. Hormone effects (200ng/l) on IKs and IKr were assessed in CHO-KCNQ1-KCNE1 and HEK-HERG cells.
Results: OXY steepened QT/RR ratio (0.62±0.1 vs. OXY 0.71±0.1, p=0.001). PRL did not alter QT/RR (0.62±0.1 vs. PRL 0.68±0.2) but slowed the heart rate (RR, ms, 324±55 vs. PRL 418±82, p<0.001).
OXY prolonged APD already at low concentrations (APD75, ms, basal vs. 20ng/l OXY, LVapex 136±19 vs. 154±15, p<0.001, LVmid-lat 136±9 vs. 145±0.1, p<0.01, LVbase-sept 137±17 vs. 147±18, p<0.01). PRL prolonged APD mainly at highest concentrations - particularly in RV (APD75, ms, basal vs. 200ng/l, 135±27 vs. 148±18, p<0.05). As underlying mechanisms, we identified an OXY-induced reduction of IKs tail (-25.5%, pA/pF, 70±13 vs. OXY 57±13, p<0.001) and IKs steady (-22.9%, 210±35 vs. OXY 170±36, p<0.001) and a less pronounced PRL-induced reduction of IKs tail (-18.5%, p<0.05) and IKs steady (-17.8%, p<0.05). IKr currents were not altered.
Furthermore, postpartum hormones increased the following mRNA levels: OXY increased CACB in LVbase (1.3-fold, p<0.05) and SEPTapex (1.5-fold, p<0.01) and RYR2 in RVapex (1.4-fold, p<0.01). PRL increased CACB in SEPTmid (1.2-fold, p<0.05), SEPTapex (1.6-fold, p<0.01), RVbase (1.3-fold, p<0.05) and RYR2 in LVmid (1.5-fold, p<0.05), SEPTmid (1.4-fold, p<0.05), and RVbase (1.4-fold, p<0.05).
Conclusions: OXY-induced prolongation of cardiac repolarization and PRL-induced slowing of heart rate as well as their effects on repolarizing IKs and CACB and RyR expression may contribute to the increased postpartal arrhythmogenic risk in LQT2.
- © 2013 by American Heart Association, Inc.