Original Paper

The Journal of Physiological Sciences

, Volume 62, Issue 3, pp 221-231

First online:

Evaluation of left ventricular mechanical work and energetics of normal hearts in SERCA2a transgenic rats

  • Guo-Xing ZhangAffiliated withDepartment of Physiology II, Nara Medical University School of MedicineDepartment of Physiology, Medical College of Soochow University
  • , Koji ObataAffiliated withDepartment of Physiology II, Nara Medical University School of Medicine
  • , Daisuke TakeshitaAffiliated withDepartment of Physiology II, Nara Medical University School of Medicine
  • , Shinichi MitsuyamaAffiliated withDepartment of Physiology II, Nara Medical University School of Medicine
  • , Tamiji NakashimaAffiliated withDepartment of Anatomy, School of Medicine, University of Occupational and Environmental Health
  • , Akio KikutaAffiliated withDepartment of Anatomy, School of Medicine, University of Occupational and Environmental Health
  • , Masumi HirabayashiAffiliated withNational Institute for Physiological Sciences
  • , Koichi TomitaAffiliated withNational Institute for Physiological Sciences
  • , Roland VetterAffiliated withInstitut für Klinische Pharmakologie und Toxikologie, Charité-Universitätsmedizin Berlin
    • , Wolfgang H. DillmannAffiliated withDepartment of Medicine, University of California, San Diego
    • , Miyako TakakiAffiliated withDepartment of Physiology II, Nara Medical University School of Medicine Email author 

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Abstract

Cardiac sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) is responsible for most of the Ca2+ removal during diastole and a larger Ca2+ handling energy consumer in excitation–contraction (E–C) coupling. To understand the cardiac performance under long-term SERCA2a overexpression conditions, we established SERCA2a transgenic (TG) Wistar rats to analyze cardiac mechanical work and energetics in normal hearts during pacing at 300 beats/min. SERCA2a protein expression was increased in TGI and TGII rats (F2 and F3 of the same father and different mothers). Mean left ventricular (LV) end-systolic pressure (ESP) and systolic pressure–volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) were significantly larger in TGI rats and were unchanged in TGII rats, compared to those in non-TG [wildtype (WT)] littermates. Mean myocardial oxygen consumption per minute for E–C coupling was significantly increased, and the mean slope of myocardial oxygen consumption per beat (VO2)–PVA (systolic PVA) linear relation was smaller, but the overall O2 cost of LV contractility for Ca2+ is unchanged in all TG rats. Mean Ca2+ concentration exerting maximal ESPmLVV in TGII rats was significantly higher than that in WT rats. The Ca2+ overloading protocol did not elicit mitochondrial swelling in TGII rats. Tolerance to higher Ca2+ concentrations may support the possibility for enhanced SERCA2a activity in TGII rats. In conclusion, long-term SERCA2a overexpression enhanced or maintained LV mechanics, improved contractile efficiency under higher energy expenditure for Ca2+ handling, and improved Ca2+ tolerance, but it did not change the overall O2 cost of LV contractility for Ca2+ in normal hearts of TG rats.

Keywords

Pressure–volume area SERCA2a Transgenic rat