Description:
<jats:p>RNA binding motif 20 (<jats:italic>Rbm20</jats:italic>) is a muscle‐specific splicing factor that mainly regulates isoform transition of titin, a giant sarcomeric protein responsible for diastolic properties of the heart. <jats:italic>Rbm20<jats:sup>‐/‐</jats:sup></jats:italic> (KO) rats fail to splice titin from fetal to adult isoforms, resulting in less stiff ventricular walls and thus systolic dysfunction and heart failure. Although previous data have shown that ejection fraction in KO rats is significantly lower than that of <jats:italic>Rbm20<jats:sup>+/+</jats:sup></jats:italic> (WT) rats in 10 m old rats, little is known of cardiac function in KO rats versus age‐matched WT rats with development using pressure volume loop analysis. We hypothesized that KO rats would develop dysfunction early in life. Preliminary results of 6 m old rats (n=8 per group) show significant (p<0.05) decreases in cardiac output (KO 18.6±2.1; WT, 43.0±2.9 mL•min<jats:sup>‐1</jats:sup>), heart rate (KO, 215.0±12.9; WT, 274.4±18.5 b•min<jats:sup>‐1</jats:sup>), stroke volume (KO, 85.2±4.9; WT, 156.9±3.3 µL), ejection fraction (KO, 30.2±5.0; WT, 53.5±6.6 %), stroke work (KO, 6.17±0.60; WT, 13.0±0.80 mmHg•mL), and cardiac efficiency (KO, 0.464±0.031; WT, 0.655±0.073). End‐systolic elastance was significantly lower in KO (KO, 0.405±0.094; WT, 0.825±0.063 mmHg•µL<jats:sup>‐1</jats:sup>), indicating an increase in systolic compliance, while neither end‐diastolic elastance (KO, 0.095±0.030; WT, 0.040±0.003 mmHg•µL<jats:sup>‐1</jats:sup>) nor Tau (KO<jats:italic>,</jats:italic> 13.5±1.48; WT, 12.8±0.85 ms), both indexes of diastolic compliance, were different. We conclude that KO rats show significant evidence of heart failure as early as 6 m of age.</jats:p><jats:p>Supported by NIH P20 GM103432, the University of WY Agricultural Experimental Station, and USDA‐NIFA.</jats:p>