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Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts

¹Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; ²Department of Physiology II, Nara Medical University School of Medicine, Kashihara, Nara, Japan; and ³Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea

Submitted 29 November 2006 ; accepted in final form 9 January 2007

The aim of this study was to examine how global cardiac gene transfer of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) can influence left ventricular (LV) mechanical and energetic function, especially in terms of O₂ cost of LV contractility, in normal rats. Normal rats were randomized to receive an adenovirus carrying the SERCA2a (SERCA) or -galactosidase (-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, -Gal, and saline groups. Moreover, the LV relaxation rate was faster in the SERCA group. There was no significant difference in myocardial O₂ consumption per beat-systolic pressure-volume area relation among the groups. Finally, O₂ cost of LV contractility was decreased to subnormal levels in the SERCA group but remained unchanged in the -Gal and saline groups. This lowered O₂ cost of LV contractility in SERCA hearts indicates energy saving in Ca²⁺ handling during excitation-contraction coupling. Thus overexpression of SERCA2a transformed the normal energy utilization to a more efficient state in Ca²⁺ handling and superinduced the supranormal contraction/relaxation due to enhanced Ca²⁺ handling.

contractile function; energetics; oxygen consumption; SERCA2a

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