{"id":6341,"date":"2023-02-17T07:03:41","date_gmt":"2023-02-17T07:03:41","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-postpartum-hormones-oxytocin-and-prolactin-cause-pro-arrhythmic-prolongation-of-cardiac-repolarization-in-long-qt-syndrome-type-2\/"},"modified":"2023-02-17T07:03:41","modified_gmt":"2023-02-17T07:03:41","slug":"2019-postpartum-hormones-oxytocin-and-prolactin-cause-pro-arrhythmic-prolongation-of-cardiac-repolarization-in-long-qt-syndrome-type-2","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2019-postpartum-hormones-oxytocin-and-prolactin-cause-pro-arrhythmic-prolongation-of-cardiac-repolarization-in-long-qt-syndrome-type-2\/","title":{"rendered":"2019 &#8211; Postpartum hormones oxytocin and prolactin cause pro-arrhythmic prolongation of cardiac repolarization in long QT syndrome type 2"},"content":{"rendered":"<p>AimsWomen with long QT syndrome 2 (LQT2) have a particularly high postpartal risk for lethal arrhythmias. We aimed at investigating whether oxytocin and prolactin contribute to this risk by affecting repolarization.Methods and resultsIn female transgenic LQT2\u00a0rabbits (HERG-G628S, loss of I<sup>Kr<\/sup>), hormone effects on QT\/action potential duration (APD) were assessed (0.2\u2013200\u2009ng\/L). Hormone effects (200\u2009ng\/L) on ion currents and cellular APD were determined in transfected cells and LQT2\u00a0cardiomyocytes. Hormone effects on ion channels were assessed with qPCR and western blot. Experimental data were incorporated into\u00a0in silico\u00a0models to determine the pro-arrhythmic potential. Oxytocin prolonged QTc and steepened QT\/RR-slope\u00a0in vivo\u00a0and prolonged ex vivo APD75\u00a0in LQT2\u00a0hearts. Prolactin prolonged APD75\u00a0at high concentrations. As underlying mechanisms, we identified an oxytocin- and prolactin-induced acute reduction of IKs-tail and IKs-steady (\u221225.5%, oxytocin; \u221213.3%, prolactin, P\u2009<\u20090.05) in CHO-cells and LQT2-cardiomyocytes. I<sup>Kr<\/sup>\u00a0currents were not altered. This oxytocin-\/prolactin-induced IKs\u00a0reduction caused APD90\u00a0prolongation (+11.9%\/+13%, P\u2009<\u20090.05) in the context of reduced\/absent I<sup>Kr<\/sup>\u00a0in LQT2\u00a0cardiomyocytes. Hormones had no effect on IK1\u00a0and ICa,L\u00a0in cardiomyocytes. Protein and mRNA levels of CACNA1C\/CaV1.2 and RyR2 were enhanced by oxytocin and prolactin. Incorporating these hormone effects into computational models resulted in reduced repolarization reserve and increased propensity to pro-arrhythmic permanent depolarization, lack of capture and early afterdepolarizations formation.ConclusionsPostpartum hormones oxytocin and prolactin prolong QT\/APD in LQT2\u00a0by reducing IKs\u00a0and by increasing CaV1.2 and RyR2 expression\/transcription, thereby contributing to the increased postpartal arrhythmic risk in LQT2.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[61,335],"target_families":[333,336,340],"targets":[91,92,95,258],"resource_keyword":[],"class_list":["post-6341","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","target_categories-voltage-gated-ion-channels","target_categories-intracellular-regulated-ion-channels","target_families-kv-channels","target_families-calcium-release-receptors","target_families-cav-channels","targets-cav1-2","targets-kv11-1-herg","targets-kv7-1","targets-ryrs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6341","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6341"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6341"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6341"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6341"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6341"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6341"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6341"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6341"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6341"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}