β-blockers are not routinely prescribed in pulmonary artery hypertension (PAH) and right ventricle (RV) failure, however recent small scale clinical studies suggest they may be safe or beneficial [1,2]. We show chronic administration of the β1 blocker, metoprolol, in a rat model of PAH prolongs survival and partially restores abnormal Ca2+ handling and contractility to RV myocytes. Male Wistar rats were injected with 60 mg/kg monocrotaline (MCT) to induce PAH; metoprolol or placebo treatment was initiated 15 days after MCT injection. Experiments were performed when placebo-treated MCT rats developed symptoms of heart failure (FAIL n=13) such as weight loss or dyspnoea; metoprolol treated MCT (MCT+BB n=12) and saline-injected control (CON n=16) rats were used on the median survival day (±1) of FAIL rats to compare RV function at temporally equivalent points. Rats were humanely killed by stunning and cervical dislocation. The heart was removed and single RV myocytes isolated. Cells were stimulated to contract between 1-7 Hz. T-tubules were analysed in di-8-ANNEPS (5μM) loaded cells using a fast Fourier transform (FFT). Intracellular Ca2+ transients were monitored using Fura-4F-AM (2μM) or Fluo-4-AM (6μM). Experiments were performed at 37±1 or 22±1°C. Data are presented as mean±SEM. One-way ANOVA or two-way repeated measures ANOVA were used as appropriate. P<0.05 was considered significant. The median time for FAIL rats to develop symptoms of heart failure was 24 days; a group of metoprolol-treated MCT rats (n=7) were monitored until symptoms of heart failure developed (median day 31, P<0.05 vs FAIL, Mantel-Cox test). The T-tubule network was disrupted in FAIL cells (reduced amplitude of the FFT first harmonic), but restored to CON levels in MCT+BB cells (FAIL 17.5±2.4 a.u., MCT+BB 88.0±13.6 a.u., CON 63.8±9.2 a.u., n=7-30 cells, P<0.001). Spatiotemporal homogeneity of systolic Ca2+ release was measured in confocal linescan mode as the coefficient of variation (CV%) in Fluo-4 fluorescence at the beginning of a Ca2+ transient; Ca2+ release CV% increased in FAIL cells indicating reduced homogeneity, but was restored to CON levels in MCT+BB cells (FAIL 27.2±0.9%, MCT+BB 21.2±1.0%, CON 23.3±0.9%, n=43-50 cells, P<0.05). FAIL cell fractional shortening decreased steeply as pacing frequency increased from 1-7Hz, whereas CON cell shortening increased and MCT+BB cells were intermediate between CON and FAIL; simultaneous recording of Ca2+ transient amplitude showed a similar relationship (n=28-30 cells per group). Improved Ca2+ handling in RV myocytes from PAH rats treated with metoprolol may delay the onset of heart failure through preservation of RV function. β-blockers are a potential treatment for the failing RV in PAH.