Sakata Susumu, Lebeche Djamel, Sakata Naoya, Sakata Yuri, Chemaly Elie R, Liang Li Fan, Takewa Yoshiaki, Jeong Dongtak, Park Woo Jin, Kawase Yoshiaki, Hajjar Roger J
Mount Sinai School of Medicine, Atran Laboratory Building, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2356-63. doi: 10.1152/ajpheart.01310.2006. Epub 2007 Jan 12.
The aim of this study was to examine how global cardiac gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) can influence left ventricular (LV) mechanical and energetic function, especially in terms of O(2) cost of LV contractility, in normal rats. Normal rats were randomized to receive an adenovirus carrying the SERCA2a (SERCA) or beta-galactosidase (beta-Gal) gene or saline by a catheter-based technique. LV mechanical and energetic function was measured in cross-circulated heart preparations 2-3 days after the infection. The end-systolic pressure-volume relation was shifted upward, end-systolic pressure at 0.1 ml of intraballoon water volume was higher, and equivalent maximal elastance, i.e., enhanced LV contractility, was higher in the SERCA group than in the normal, beta-Gal, and saline groups. Moreover, the LV relaxation rate was faster in the SERCA group. There was no significant difference in myocardial O(2) consumption per beat-systolic pressure-volume area relation among the groups. Finally, O(2) cost of LV contractility was decreased to subnormal levels in the SERCA group but remained unchanged in the beta-Gal and saline groups. This lowered O(2) cost of LV contractility in SERCA hearts indicates energy saving in Ca(2+) handling during excitation-contraction coupling. Thus overexpression of SERCA2a transformed the normal energy utilization to a more efficient state in Ca(2+) handling and superinduced the supranormal contraction/relaxation due to enhanced Ca(2+) handling.
本研究的目的是探讨在正常大鼠中，肌浆网Ca(2+) -ATP酶（SERCA2a）的整体心脏基因转移如何影响左心室（LV）的机械和能量功能，特别是在LV收缩性的氧消耗方面。通过基于导管的技术，将正常大鼠随机分为接受携带SERCA2a（SERCA）或β-半乳糖苷酶（β-Gal）基因的腺病毒或生理盐水组。在感染后2 - 3天，在交叉循环心脏标本中测量LV的机械和能量功能。与正常组、β-Gal组和生理盐水组相比，SERCA组的收缩末期压力-容积关系向上移位；球囊内水体积为0.1 ml时的收缩末期压力更高；等效最大弹性，即增强的LV收缩性更高。此外，SERCA组的LV舒张速率更快。各组之间每搏收缩期压力-容积面积关系的心肌氧消耗无显著差异。最后，SERCA组LV收缩性的氧消耗降至低于正常水平，而β-Gal组和生理盐水组则保持不变。SERCA心脏中LV收缩性的这种降低的氧消耗表明在兴奋-收缩偶联期间Ca(2+)处理过程中的能量节约。因此，SERCA2a的过表达将正常的能量利用转变为Ca(2+)处理中更有效的状态，并由于增强的Ca(2+)处理而超诱导超常收缩/舒张。
