A Novel Technique of Cardiomyoplasty with Autologous Myotissue Implant into Myocardial Infarct Zone in a Porcine Myocardial Infarction Model

Yun, Seong Hun; Lee, Seung Uk; Lee, Kwang Wook; Kim, Jong Hwan; Park, Oh Sung; Kang, Dong Goo; Ko, Young Chun; Cho, Sang Ki; Laham, Roger J

Abstract

Cellular therapy has been used to prevent post-infarction myocardial dysfunction. This, however, is limited by poor cell survival and need for cell manipulation. We present the results of this new cardiomyoplasty technique in the treatment of healed myocardial infarction and explore further potential mechanisms responsible for this effect. Twelve Yorkshire pigs underwent myocardial infarction via balloon occlusion for one hour. Two weeks after the initial infarct, animals were randomized to (1) treatment group (n=6) undergoing septal biopsies via the right ventricle and implantation of 6~10 biopsies in the left ventricular anterior wall or, (2) control group (n=6) undergoing septal biopsies and sham injections. All animals were sacrificed four weeks after infartion. Tetrazolium (TTC) staining demonstrated significantly smaller infarcts in the left ventricular anterior wall in treated animals than in controls (21.4+/-3.3% versus 33.4+/-2.2%, p=0.006). There was a significant difference in the infarct size in the untreated septum (16.2+/-3.3% and 27.1+/-3%, p=0.024). Ejection fraction (EF) remained the same in the treated animals at weeks 2 and 4 (49+/-6.5% vs 46+/-7.4%, p=0.52). In contrast, EF decreased significantly in untreated animals (50+/-10.4% vs 36+/-8.7%, p=0.038) using blind echocardiographic assessment. On gross pathology and H&E staining myocardial implants were viable with nearly 100% engraftment within the scar area at 4 weeks post infarction. Infarcts in animals treated with cardiomyoplasty contained significantly more mdr-1+ cardiac stem cells per high power field (9+/-6 vs 17+/-3, p=0.038) but lower numbers of c-kit+ stem cells (0.6+/-1.3 vs 7.8+/-6, p=0.0334) and equal numbers of sca-1+ stem cells. MMP-2 levels tended to be two-fold lower in treated animals and conversely, TIMP-2 levels were two-fold higher. VEGF-2 levels tended to be lower in treated animals. This novel method of implanting autologous adult myocardial cells is safe and efficacious in limiting left ventricular dysfunction in the setting of infarction. Implanting myocardial tissue in its entirety with preserved extracellular matrix milieu may have enhanced its viability. Implanted tissue contained cardiac stem cells that may have contributed to preservation of myocardial function.