Cell transplantation prevents cardiac dysfunction following myocardial infarction. However, since most implanted cells are lost to ischemia and apoptosis, the benefits of cell transplantation on heart function could be improved by increasing cell survival. To examine this possibility, male Lewis rat aortic smooth muscle cells (SMCs, 4X10⁶) were pretreated with anti-apoptotic Bcl-2 gene transfection (BCL) or heat shock (HS), then implanted into the infarcted myocardium of anesthetized, syngenic female rats (N=23 per group). On the first day after transplantation, apoptotic SMCs were quantified using TUNEL staining. On days 7 and 28, grafted cell survival was quantified using real-time PCR, and heart function was assessed using echocardiography and the Langendorff apparatus. SMCs given anti-apoptotic pretreatments exhibited improvements in each measure relative to controls. Apoptosis was reduced in Bcl-2-treated cells relative to all other groups (p<0.05), while survival (p<0.01) was increased. Heat shock also significantly decreased apoptosis and increased survival relative to control groups (p<0.05 for group effect), though these effects were less pronounced than in the BCL group. Further, scar areas were reduced in both Bcl-2 and heat shock-treated groups relative to controls (p<0.05), and fractional area change and cardiac function were greater (p<0.05 for both measures). These results indicate that anti-apoptosis pretreatments reduced grafted smooth muscle cell loss after transplantation and enhanced grafted cell survival and ventricular function, which was directly related (r=0.72; p =0.002) to the number of surviving engrafted cells.