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

Abstract

Cardiac sarcoplasmic reticulum (SR) Ca 2+-ATPase (SERCA2a) is responsible for most of the Ca 2+ removal during diastole and a larger Ca 2+ 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 (VO 2)-PVA (systolic PVA) linear relation was smaller, but the overall O2 cost of LV contractility for Ca 2+ is unchanged in all TG rats. Mean Ca 2+ concentration exerting maximal ESPmLVV in TGII rats was significantly higher than that in WT rats. The Ca 2+ overloading protocol did not elicit mitochondrial swelling in TGII rats. Tolerance to higher Ca 2+ 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 Ca 2+ handling, and improved Ca 2+ tolerance, but it did not change the overall O2 cost of LV contractility for Ca 2+ in normal hearts of TG rats. © 2012 The Physiological Society of Japan and Springer.