Key result
DOCA-induced chronic arterial hypertension in pigs significantly reduced left atrial contractile ejection fraction (23% vs 38%, P<0.05) due to impaired cardiomyocyte calcium release.
Why the study?
Atrial contractile dysfunction contributes to worse prognosis in hypertensive heart disease, but the role of cardiomyocyte dysfunction in atrial remodelling is not well understood.
In a pig model of hypertensive heart disease, atrial remodeling and dysfunction are driven by differential left and right atrial cardiomyocyte Ca2+ handling abnormalities, which can be partially improved in the left atrium by NCX inhibition.
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.
No takes yet. Share an insight, caveat, or question.
Jin et al. (2020) studied Hypertensive heart disease (n=47). 11-deoxycorticosterone acetate (DOCA) and high-salt/glucose diet vs. Healthy control pigs was evaluated on Left atrial contractile ejection fraction (p=<0.05). DOCA-induced chronic arterial hypertension in pigs significantly reduced left atrial contractile ejection fraction (23% vs 38%, P<0.05) due to impaired cardiomyocyte calcium release.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: