Cellular Mechanisms Underlying the Low Cardiotoxicity of Istaroxime.

ABSTRACT: Background Istaroxime is an inhibitor of Na⁺/K⁺ ATPase with proven efficacy to increase cardiac contractility and to accelerate relaxation attributable to a relief in phospholamban-dependent inhibition of the sarcoplasmic reticulum Ca²⁺ ATPase. We have previously shown that pharmacologic Na⁺/K⁺ ATPase inhibition promotes calcium/calmodulin-dependent kinase II activation, which mediates both cardiomyocyte death and arrhythmias. Here, we aim to compare the cardiotoxic effects promoted by classic pharmacologic Na⁺/K⁺ ATPase inhibition versus istaroxime. Methods and Results Ventricular cardiomyocytes were treated with ouabain or istaroxime at previously tested equi-inotropic concentrations to compare their impact on c

SUBMITTER: Racioppi MF 

PROVIDER: S-EPMC8483492 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature