Exercise training normalizes altered calcium-handling proteins during development of heart failure

Divisions of 1 Circulatory Physiology and 5 Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City 10032; 2 Bronx Sciences High School, Bronx; 3 Division of Cardiology, Mt. Sinai Medical Center, New York, New York 10021; and 4 Division of Cardiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107 The cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), Na + /Ca 2+ exchanger (NCX1), and ryanodine receptor (RyR2) are proteins involved in the regulation of myocyte calcium. We tested whether exercise training (ET) alters those proteins during development of chronic heart failure (CHF). Ten dogs were chronically instrumented to permit hemodynamic measurements. Five dogs underwent 4 wk of cardiac pacing (210 beats/min for 3 wk and 240 beats/min for the 4th wk), whereas five dogs underwent the same pacing regimen plus daily ET (5.1 ± 0.3 km/h, 2 h/day). Paced animals developed CHF characterized by hemodynamic abnormalities and reduced ejection fraction. ET preserved resting hemodynamics and ejection fraction. Left ventricular samples were obtained from all dogs and another five normal dogs for mRNA (Northern analysis, band intensities normalized to glyceraldehyde-3-phosphate dehydrogenase) and protein level (Western analysis, band intensities normalized to tubulin) measurements. In failing hearts, SERCA2a was decreased by 33% ( P