BACKGROUND: The feasibility of successfully grafting fetal cardiomyocytes into infarcted myocardium is now established, but the functional effects of such a procedure still remain elusive. METHODS AND RESULTS: Twenty-three female rats underwent 45 minutes of coronary artery occlusion followed by 30 minutes of reperfusion. At this time point, 13 animals received intramyocardial injections of fetal cardiomyocytes (6 x 10(6) cells in 60 microL of culture medium) in the once ischemic area, whereas the 10 control rats were injected with an equivalent volume of culture medium alone. One month after transplantation, left ventricular function was assessed by two-dimensional (2D) and Doppler echocardiography using a short focus 10- to 13-MHz transducer, and a numeric acquisition of 2D images up to 65.5 frames/second. Explanted hearts were then processed for histological assessment of infarct size. The presence of male donor cells into female recipient myocardium was detected by fluorescent in situ hybridization using a deoxyribonucleic acid probe specific for Y chromosome. Cellular transplantation resulted in an improved left ventricular function, as demonstrated by significantly higher 2D ejection fraction and cardiac output (P<.02 and P<.02 versus control hearts, respectively). The histological sections of female recipient myocardium were Y-positive in all but one heart, thereby suggesting that this improvement of function was causally related to the presence of transplanted cells. CONCLUSIONS: These data suggest that transplantation of cardiomyocytes might be an effective means of improving function of infarcted myocardium.