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SHR Neuro Krebs Kardio Lipid

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-H1418 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Alogna Alessio
Eller Kathrin
Eller Philipp
Hoefler Gerald
Kirsch Alexander
Maechler Heinrich
Manninger-Wünscher Martin
Pieske Burkert Mathias
Post Heiner
Schwarzl Michael
Verderber Jochen
Zirngast Birgit
Zweiker David

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Plum 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. Copyright © 2015 the American Physiological Society.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cardiomyopathies - etiology
Cardiomyopathies - metabolism
Cardiomyopathies - pathology
Cardiomyopathies - physiopathology
Connectin - metabolism
Desoxycorticosterone Acetate - toxicity
Diet, Western -
Dilatation, Pathologic - etiology
Dilatation, Pathologic - physiopathology
Disease Models, Animal -
Female -
Heart Atria - physiopathology
Heart Failure - etiology
Heart Failure - metabolism
Heart Failure - pathology
Heart Failure - physiopathology
Hyperlipidemias - chemically induced
Hyperlipidemias - complications
Hypertension - chemically induced
Hypertension - complications
Hypertrophy - etiology
Hypertrophy - pathology
Hypertrophy, Left Ventricular - etiology
Hypertrophy, Left Ventricular - metabolism
Hypertrophy, Left Ventricular - pathology
Hypertrophy, Left Ventricular - physiopathology
Mineralocorticoids - toxicity
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Nitric Oxide Synthase - metabolism
Phosphorylation -
Protein Isoforms - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Stroke Volume -
Superoxides - metabolism
Swine -

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