Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction

Background-Myocardial infarction (MI) promotes deleterious remodeling of th e myocardium, resulting in ventricular dilation and pump dysfunction. We ex amined whether supplementing infarcted myocardium with skeletal myoblasts w ould (1) result in viable myoblast implants, (2) attenuate deleterious remo deling, and (3) enhance in vivo and ex vivo contractile performance. Methods and Results-Experimental MT was induced by I-hour coronary ligation followed by reperfusion in adult male Lewis rats. One week after MI, 10(6) myoblasts were injected directly into the infarct region. Three groups of animals were studied at 3 and 6 weeks after cell therapy: noninfarcted cont rol (control), MI plus sham injection (MI). and MI plus cell injection (MIcell). In vivo cardiac function was assessed by maximum exercise capacity t esting and ex vivo function was determined by pressure-volume curves obtain ed from isolated, red cell-perfused, balloon-in-left ventricle (LV) hearts. MI and MI+cell hearts had indistinguishable infarct sizes of approximate t o 30% of the LV. At 3 and 6 weeks after cell therapy, 92% (13 of 14) of MIcell hearts showed evidence of myoblast graft survival. MI+cell hearts exhi bited attenuation of global ventricular dilation and reduced septum-to-free wall diameter compared with MI hearts not receiving cell therapy. Furtherm ore, cell therapy improved both post-Mi in vivo exercise capacity and ex vi vo LV systolic pressures. Conclusions-Implanted skeletal myoblasts form viable grafts in infarcted my ocardium, resulting in enhanced post-MI exercise capacity and contractile f unction and attenuated ventricular dilation. These data illustrate that syn geneic myoblast implantation after MI improves both in vivo and ex vivo ind exes of global ventricular dysfunction and deleterious remodeling and sugge sts that cellular implantation may be beneficial after MI.