The aim was to examine the efficiency of adenovirus-mediated overexpression of sarcoplasmic reticulum calcium ATPase (SERCA1a) gene in a realistic model based on percutaneous intracoronary delivery and on non invasive functional monitoring. Catheter-based selective coronary delivery of saline or adenoviruses (Ad.CMV.SERCA1a or Ad.CMV.lacZ, 10¹⁰ pfu) was performed in the circumflex artery of rabbits. Effects were assessed and compared using serial Doppler-echocardiography, hemodynamics and measurements of SERCA protein and calcium uptake activity. On day 3, a 21% increase in SERCA proteins and a 37% increase in the maximal rate of calcium uptake was 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 asses 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 calcium 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 more 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 accurate and non-invasive tool for monitoring effects on global as well as regional myocardial function.