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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1773    most recent 00411.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Logeart, D. Articles by Mercadier, J.-J. Search for Related Content PubMed PubMed Citation Articles by Logeart, D. Articles by Mercadier, J.-J.

Percutaneous intracoronary delivery of SERCA gene increases myocardial function: a tissue Doppler imaging echocardiographic study

¹Institut National de la Santé et de la Recherche Médicale U698, Bichat Hospital; ²Assistance Publique-Hôpitaux de Paris, Lariboisière Hospital, Department of Cardiology, Paris; ³Centre Nationale de Recherche Scientifique UMR 1582, Institut Gustave Roussy, Villejuif; and ⁴Institut National de la Santé et de la Recherche Médicale U722, Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Paris, France

Submitted 20 April 2006 ; accepted in final form 16 May 2006

The aim of this study was to examine the efficiency of adenovirus-mediated overexpression of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA1a) gene in a realistic model based on percutaneous intracoronary delivery and on noninvasive functional monitoring. Catheter-based selective coronary delivery of saline or adenoviruses (Ad.CMV.SERCA1a or Ad.CMV.lacZ, 10¹⁰ plaque-forming units) was performed in the circumflex artery of rabbits. Effects were assessed and compared by using serial Doppler echocardiography, hemodynamics, and measurements of SERCA protein and Ca²⁺ uptake activity. On day 3, a 21% increase in SERCA proteins and a 37% increase in the maximal rate of Ca²⁺ uptake were observed in the transfected left ventricular (LV) walls of Ad.CMV.SERCA1a rabbits. Baseline hemodynamics and conventional echographic measurements of global LV function were poorly affected. In contrast, tissue Doppler imaging (TDI) was able to assess a strong increase in the baseline function of transfected LV walls, as assessed with maximal wall velocities (+32% and +43%, respectively) and strain rates (+18% and +30%, respectively). TDI parameters were closely related to the maximal rate of Ca²⁺ uptake (r² = 0.68 for the systolic strain rate). Serial TDI analysis during follow-up showed that the effects lasted for 7 days and were no longer detectable 15 days after adenoviruses injection. In conclusion, LV function can be increased by adenovirus-mediated overexpression of SERCA in a clinically relevant model, and TDI provides an accurate and noninvasive tool for monitoring effects on global as well as regional myocardial function.

gene therapy; ventricular function; sarco(endo)plasmic reticulum Ca²⁺-ATPase; echocardiography

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