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

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Schwarzl, M; Hamdani, N; Seiler, S; Alogna, A; Manninger, M; Reilly, S; Zirngast, B; Kirsch, A; Steendijk, P; Verderber, J; Zweiker, D; Eller, P; Höfler, G; Schauer, S; Eller, K; Maechler, H; Pieske, BM; Linke, WA; Casadei, B; Post, H.
A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.
Am J Physiol Heart Circ Physiol. 2015; 309(9):H1407-18 Doi: 10.1152/ajpheart.00542.2015 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Post Heiner
Schwarzl Michael
Co-Autor*innen der Med Uni Graz
Albori Jochen
Alogna Alessio
Eller Kathrin
Eller Philipp
Höfler Gerald
Kirsch Alexander
Mächler Heinrich
Manninger-Wünscher Martin
Pieske Burkert Mathias
Zirngast Birgit
Zweiker David

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Cardiomyopathies - etiology, metabolism, pathology, physiopathology
Connectin - metabolism
Desoxycorticosterone Acetate - toxicity
Diet, Western - administration & dosage
Dilatation, Pathologic - etiology, physiopathology
Disease Models, Animal - administration & dosage
Female - administration & dosage
Heart Atria - physiopathology
Heart Failure - etiology, metabolism, pathology, physiopathology
Hyperlipidemias - chemically induced, complications
Hypertension - chemically induced, complications
Hypertrophy - etiology, pathology
Hypertrophy, Left Ventricular - etiology, metabolism, pathology, physiopathology
Mineralocorticoids - toxicity
Myocytes, Cardiac - metabolism, pathology
Nitric Oxide Synthase - metabolism
Phosphorylation - administration & dosage
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Stroke Volume - administration & dosage
Superoxides - metabolism
Swine - administration & dosage

Find related publications in this database (Keywords)
heart failure with preserved ejection fraction
hypertensive heart disease
pressure-volume analysis
oxidative stress
© Med Uni Graz Impressum