A hypoxia-on-a-chip platform for modeling ischemic arrhythmogenesis and evaluating the effects of levosimendan and OR-1896 on ischemic human iPSC-derived cardiomyocytes.

ABSTRACT: Acute hypoxia is a major contributor to cardiomyocyte damage and dysfunction in ischemic heart disease, and the effective therapeutic strategies remain limited. Levosimendan, a calcium sensitizer with both inotropic and vasodilatory effects, along with its active metabolite OR-1896, is utilized in the treatment of acute heart failure. In this study, we investigated the cardioprotective and antiarrhythmic effects of levosimendan and its metabolite OR-1896 under hypoxic conditions using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were exposed to acute hypoxia and treated with levosimendan or its metabolite OR-1896. Structural integrity was assessed via immunostaining and electron microscopy imaging. Calcium transient abnormalities were evaluated using li

SUBMITTER: Gaballah M 

PROVIDER: S-EPMC12515882 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature