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Nitroxyl (HNO)
- Source :
- Circulation: Heart Failure. 6:1250-1258
- Publication Year :
- 2013
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2013.
-
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 t 1/2 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 soluble guanylate cyclase altered this contractile response. Unlike isoproterenol, CXL-1020 was equally effective in myocytes from normal or failing hearts. In anesthetized dogs with coronary microembolization-induced HF, CXL-1020 reduced left ventricular end-diastolic pressure and myocardial oxygen consumption while increasing ejection fraction from 27% to 40% and maximal ventricular power index by 42% (both P Conclusions— These data show the functional efficacy of a novel pure HNO donor to enhance myocardial function and present first-in-man evidence for its potential usefulness in HF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01096043, NCT01092325.
- Subjects :
- Male
Inotrope
medicine.medical_specialty
Lusitropy
Free Radicals
Antioxidants
Ventricular Function, Left
Article
Mice
Dogs
Internal medicine
Heart rate
medicine
Animals
Humans
Myocytes, Cardiac
Heart Failure
Ejection fraction
Dose-Response Relationship, Drug
business.industry
Stroke Volume
Stroke volume
medicine.disease
Myocardial Contraction
Treatment Outcome
Blood pressure
medicine.anatomical_structure
Heart failure
Cardiology
Vascular resistance
Female
Nitrogen Oxides
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 19413297 and 19413289
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Circulation: Heart Failure
- Accession number :
- edsair.doi.dedup.....b806909a9579273256d5b977935fa83d