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

Kenta Ito, Masaharu Nakayama, Faisal Hasan, Xinhua Yan, Michael D. Schneider, Beverly H. Lorell

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 [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 36°C) 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.

Original languageEnglish
Pages (from-to)1176-1182
Number of pages7
JournalCirculation
Volume107
Issue number8
DOIs
Publication statusPublished - 2003 Mar 4

Keywords

  • Calcium
  • Contractility
  • Myocytes
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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