Nitroxyl (HNO): A novel approach for the acute treatment of heart failure.

ABSTRACT:

Background

The nitroxyl (HNO) donor, Angeli's salt, exerts positive inotropic, lusitropic, and vasodilator effects in vivo that are cAMP independent. Its clinical usefulness is limited by chemical instability and cogeneration of nitrite which itself has vascular effects. Here, we report on effects of a novel, stable, pure HNO donor (CXL-1020) in isolated myoctyes and intact hearts in experimental models and in patients with heart failure (HF).

Methods and results

CXL-1020 converts solely to HNO and inactive CXL-1051 with a t1/2 of 2 minutes. In adult mouse ventricular myocytes, it dose dependently increased sarcomere shortening by 75% to 210% (50-500 μmol/L), with a ≈30% rise in the peak Ca(2+) transient only at higher doses. Neither inhibition of protein kinase A nor solubl

SUBMITTER: Sabbah HN 

PROVIDER: S-EPMC4110196 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature