Right ventricular (RV) function is the most important prognostic factor for patients with pulmonary hypertension. Chronically increased afterload from any cause results in right ventricular failure (RVF). However, the pathophysiological processes that promote RVF are still understudied.

We assessed the Ca2+ dynamic in RV hypertrophy and dysfunction induced by pulmonary artery banding (PAB) in rats to achieve RV overload without affecting the pulmonary vasculature.

Using two different degrees of pulmonary artery constriction (mild or severe), cellular Ca2+ imaging was performed on isolated RV cardiomyocytes at 4 weeks post-PAB and sham-operated rats.

Our results show that the mild constriction resulted in maladaptive RV hypertrophy, with chamber dilation and reduced systolic function as assessed by echocardiography. The severe constriction accentuated the RV remodeling by increasing the Fulton index and the RV thickness compared to the mild constriction procedure. However, the RV systolic dysfunction is similar between mild and severe PAB. With Fluo-4/AM-based confocal microscopy, we showed that after 4 weeks of mild pressure overload, RV cardiomyocytes had preserved [Ca2+]i transients amplitude, faster [Ca2+]i transients decay time and preserved sarcoplasmic reticulum (SR) Ca2+ load compared to sham myocytes. This was associated with a decrease in cell shortening. After severe pressure overload, RV myocytes presented larger and shorter [Ca2+]i transients and increased SR Ca2+ load associated with enhanced cell shortening.

We reveal differences in RV Ca2+ handling modulation depending on the degree of pulmonary artery constriction. This finding provides a more comprehensive analysis of the Ca2+ dynamic at different stages of RV overload.