Studies have demonstrated the feasibility of transplanting cardiomyocytes after myocardial infarction (MI). However, persistence and effects on left ventricular (LV) function have not been elucidated in long-term studies. Ventricular fetal cardiomyocytes from embryos of both sexes were injected into marginal regions of MI 4 weeks after suture occlusion of the left anterior descending artery in adult female rats. Two and 6 months after transplantation (Tx), engrafted cells were traced by immunohistochemical in situ hybridization for Y chromosomes or bromodeoxyuridine (BrdU) staining, LV dimensions and function were assessed by echocardiography, and LV pressure was assessed ex vivo in a Langendorff perfusion system. Immunohistochemistry for alpha-sarcomeric actin and Y chromosomes revealed the presence of transplanted cells in infarcted host myocardium at both 2 and 6 months. End-diastolic LV diameter markedly decreased after Tx and fractional shortening gradually increased after Tx (31.3 +/- 4.5% before Tx, 45.4 +/- 4.2% at 6 months; p<0.005). Wall area fraction and MI size were unaffected by Tx. In hearts with MI, but not in normal hearts, Tx led to the development of higher pressures (87 +/- 18 versus 38 +/- 8 mmHg, 6 months post-Tx versus nontreated). After catecholamine stimulation, both infarcted and normal hearts developed higher pressures after Tx (p<0.005), ultimately associated with reduced mortality after Tx versus nontreated. Transplanted cardiomyocyte-rich graft cells persist in host myocardium and mediate continuous improvement of LV function and survival in a rat model of MI even during long-term follow-up, possibly involving a catecholamine-sensitive mechanism.