Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts.
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.
Sakata
Susumu
S
Mount Sinai School of Medicine, Atran Laboratory Building, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA.
Lebeche
Djamel
D
Sakata
Naoya
N
Sakata
Yuri
Y
Chemaly
Elie R
ER
Liang
Li Fan
LF
Takewa
Yoshiaki
Y
Jeong
Dongtak
D
Park
Woo Jin
WJ
Kawase
Yoshiaki
Y
Hajjar
Roger J
RJ
D000818:Animals; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D010100:Oxygen / Q000737:chemistry; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000502:physiology*
D011994:Recombinant Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D010100:Oxygen