Cellular Contribution to Left and Right Atrial Dysfunction in Chronic Arterial Hypertension in Pigs

<strong>Aims</strong>: Atrial contractile dysfunction contributes to reduced cardiac output and worse prognosis. We investigate cellular mechanisms of left (LA) and right atrial (RA) contractile dysfunction in hypertensive heart disease (HHD) in pigs. <strong>Methods &amp; Results</strong>: In vivo electrophysiological and magnetic resonance imaging (MRI) studies were performed in control (CTRL) and pigs treated with DOCA/high salt/glucose (12 weeks) to induce HHD. HHD lead to significant atrial remodeling and loss of contractile function in LA with a similar trend in RA (MRI), associated with 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 LA (already at baseline) and RA myocytes (at higher frequencies) due to reduced intracellular Ca transient (CaT) amplitude (Fura 2-AM, field stimulation). LA cardiomyocytes showed reduced sarcoplasmic reticulum (SR) [Ca²⁺], whereas in RA, SR [Ca²⁺] was unchanged and SR Ca²⁺-ATPase (SERCA) activity was increased. Sodium calcium exchanger (NCX) activity was not 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 CaT amplitude and SR Ca²⁺ in LA, but not RA cells. <strong>Conclusion: </strong>HHD leads to loss of contractility and abnormal Ca²⁺ handling in LA and RA, suggesting improvement of atrial cardiomyocyte inotropy as a therpeutic target in HHD. Atrial site-specific remodeling modulates the outcome of NCX inhibitors on restoring atrial function.