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  • Title: Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts.
    Author: Ito K, Nakayama M, Hasan F, Yan X, Schneider MD, Lorell BH.
    Journal: Circulation; 2003 Mar 04; 107(8):1176-82. PubMed ID: 12615798.
    Abstract:
    BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.
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