Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jin, G; Manninger, M; Adelsmayr, G; Schwarzl, M; Alogna, A; Schönleitner, P; Zweiker, D; Blaschke, F; Sherif, M; Radulovic, S; Wakula, P; Schauer, S; Höfler, G; Reiter, U; Reiter, G; Post, H; Scherr, D; Acsai, K; Antoons, G; Pieske, B; Heinzel, FR.
Cellular contribution to left and right atrial dysfunction in chronic arterial hypertension in pigs.
ESC Heart Fail. 2021; 8(1):151-161
Doi: 10.1002/ehf2.13087
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- Führende Autor*innen der Med Uni Graz
- Heinzel Frank
- Jin Ge
- Co-Autor*innen der Med Uni Graz
- Adelsmayr Gabriel
- Alogna Alessio
- Antoons Gudrun
- Höfler Gerald
- Manninger-Wünscher Martin
- Pieske Burkert Mathias
- Post Heiner
- Radulovic Snjezana
- Reiter Gert
- Reiter Ursula
- Schauer Silvia
- Scherr Daniel
- Schönleitner Patrick
- Schwarzl Michael
- Wakula-Heinzel Paulina
- Zweiker David
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- Abstract:
- AIMS: Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease (HHD), but the role of cardiomyocyte dysfunction in atrial remodelling in HHD is not well understood. We investigated and compared cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in pigs with HHD. METHODS AND RESULTS: In vivo electrophysiological and magnetic resonance imaging studies were performed in control and pigs treated with 11-deoxycorticosterone acetate (DOCA)/high-salt/glucose diet (12 weeks) to induce HHD. HHD leads to significant atrial remodelling and loss of contractile function in LA and a similar trend in RA (magnetic resonance imaging). Atrial remodelling was associated with a higher inducibility of atrial fibrillation but unrelated to changes in atrial refractory period or fibrosis (histology). Reduced atrial function in DOCA pigs was related to reduced contraction amplitude of isolated LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca release (Fura 2-AM, field stimulation). However, Ca regulation differed in LA and RA cardiomyocytes: LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca], whereas in RA, SR [Ca] was unchanged and SR Ca2+ -ATPase activity was increased. Sodium-calcium exchanger (NCX) activity was not significantly altered. We used ORM-10103 (3 μM), a specific NCX inhibitor to improve Ca availability in LA and RA cardiomyocytes from DOCA pigs. Partial inhibition of NCX increased Ca2+ transient amplitude and SR Ca in LA, but not RA cells. CONCLUSIONS: In this large animal model of HHD, atrial remodelling in sinus rhythm in vivo was related to differential LA and RA cardiomyocyte dysfunction and Ca signalling. Selective acute inhibition of NCX improved Ca release in diseased LA cardiomyocytes, suggesting a potential therapeutic approach to improve atrial inotropy in HHD.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Calcium - metabolism
- Heart Atria - diagnostic imaging
- Hypertension - administration & dosage
- Sarcoplasmic Reticulum - metabolism
- Sodium-Calcium Exchanger - administration & dosage
- Swine - administration & dosage
- Find related publications in this database (Keywords)
- Atrial remodelling
- Calcium
- Cardiomyocytes
- Contractility
- Sodium-calcium exchanger