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


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.
Ito
Kenta
K
Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA.
Nakayama
Masaharu
M
Hasan
Faisal
F
Yan
Xinhua
X
Schneider
Michael D
MD
Lorell
Beverly H
BH
D000818:Animals; D002118:Calcium / Q000032:analysis*; D006332:Cardiomegaly / Q000378:metabolism; D002478:Cells, Cultured; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000503:physiopathology; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D020257:Ventricular Remodeling
D009124:Muscle Proteins; D002118:Calcium