Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

Article

关键词: VENTRICULAR ASSIST DEVICE;    MECHANICAL CIRCULATORY SUPPORT;    GENE-EXPRESSION;    FAILING HEARTS;    RAT HEARTS;    DILATED CARDIOMYOPATHY;    CARDIAC-HYPERTROPHY;    FAILURE;    RECOVERY;    TRANSPLANTATION;   

DOI  :  10.1161/01.CIR.0000051463.72137.96

来源: SCIE

【 摘 要 】

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 [Ca2+](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 [Ca2+](o), and 36degreesC) and in response to stimulation with high [Ca2+](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 [Ca2+](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca2+](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca2+](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca2+](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 Ca2+ ATPase and the Na+/Ca2+ 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.

【 授权许可】

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