Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Primessnig, U; Schönleitner, P; Höll, A; Pfeiffer, S; Bracic, T; Rau, T; Kapl, M; Stojakovic, T; Glasnov, T; Leineweber, K; Wakula, P; Antoons, G; Pieske, B; Heinzel, FR.
Novel pathomechanisms of cardiomyocyte dysfunction in a model of heart failure with preserved ejection fraction.
Eur J Heart Fail. 2016; 18(8):987-997 Doi: 10.1002/ejhf.524 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Heinzel Frank
Primessnig Uwe
Co-Autor*innen der Med Uni Graz
Antoons Gudrun
Bracic Taja
Höll Alexander
Kapl Martin
Pieske Burkert Mathias
Rau Thomas
Schönleitner Patrick
Stojakovic Tatjana
Wakula-Heinzel Paulina

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Heart failure with preserved ejection fraction (HFpEF) is increasingly common, but the underlying cellular mechanisms are not well understood. We investigated cardiomyocyte function and the role of SEA0400, an Na(+) /Ca(2+) exchanger (NCX) inhibitor in a rat model of chronic kidney disease (CKD) with HFpEF. Male Wistar rats were subjected to subtotal nephrectomy (NXT) or sham operation (Sham). After 8 and 24 weeks, in vivo (haemodynamics, echocardiography) and in vitro function (LV cardiomyocyte cell shortening (CS), and Ca(2+) transients (CaT)) were determined without and with SEA0400. In a subgroup of rats, SEA0400 or vehicle was given p.o. (1 mg/kg b.w.) between week 8 and 24. NXT resulted in stable compensated CKD and HFpEF [hypertrophied left ventricle, prolonged LV isovolumetric relaxation constant TAU (IVRc TAU), elevated end diastolic pressure (EDP), increased lung weight (pulmonary congestion), and preserved LV systolic function (EF, dP/dt)]. In NXT cardiomyocytes, the amplitude of CS and CaT were unchanged but relaxation and CaT decay were progressively prolonged at 8 and 24 weeks vs. Sham, individually correlating with diastolic dysfunction in vivo. NCX forward mode activity (caffeine response) was progressively reduced, while NCX protein expression was up-regulated, suggesting increased NCX reverse mode activity in NXT. SEA0400 acutely improved relaxation in NXT in vivo and in cardiomyocytes and improved cardiac remodelling and diastolic function when given chronically. This model of renal HFpEF is associated with slowed relaxation of LV cardiomyocytes. Treatment with SEA0400 improved cardiomyocyte function, remodelling, and HFpEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.
Find related publications in this database (using NLM MeSH Indexing)
Aniline Compounds - pharmacology
Animals -
Caffeine - pharmacology
Calcium - metabolism
Central Nervous System Stimulants - pharmacology
Echocardiography -
Heart Failure - complications
Heart Failure - diagnostic imaging
Heart Failure - physiopathology
Hypertrophy, Left Ventricular - complications
Hypertrophy, Left Ventricular - diagnostic imaging
Hypertrophy, Left Ventricular - physiopathology
Male -
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - physiology
Phenyl Ethers - pharmacology
Rats -
Rats, Wistar -
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - physiopathology
Sodium-Calcium Exchanger - antagonists & inhibitors
Stroke Volume -

Find related publications in this database (Keywords)
Heart failure with preserved ejection fraction
Diastolic dysfunction
Active relaxation
Ca2+ exchanger
© Med Uni Graz Impressum