Abstract 386: Grafting Efficacy, Cardiac Persistence and Organ Distribution of Mononuclear Bone Marrow Cells after Intramyocardial vs. Intracoronary Injection in Pigs with Myocardial Infarction and Reperfusion
In clinical studies on the therapeutic effect of cell therapy for acute myocardial infarction (MI), cells are applied by intracoronary (i.c.) infusion few days after MI. However, little is known about the application efficacy and mid-term persistence after i.c. injection vs. other application techniques. Here, i.c. injection was compared to intramyocardial (i.m.) injection of mononuclear bone marrow cells (MNC) in pigs after MI and reperfusion with respect to immediate efficacy of cell transfer and 24h persistence of the cells. MI was induced in 6 male pigs (2 months, 28–32 kg, ligation of the LAD, 4 h, then reperfusion, confirmed by coronary angiography). 5 days later, autologous MNC were isolated and labeled with 111Indium and 50 million cells were injected either i.c. (over-the-wire balloon, n=3) or i.m. (n=3). Treatment protocols were the same as used in clinical studies. During i.c. injection and immediately after i.m. injection dynamic scintigraphic analyses, whole body scans and SPECT analyses were performed, and repeated after 24h. 1h after i.m. injection 22±1% of total radioactivity was localized in the heart, after 24h it was 16±2% (P=0.07). The lungs had 43±3% (1h) and 39±1% (24h), the liver 13±3% (1h) and 17±1% (24h), and the spleen 3±1% and 4±2%. During i.c. application, dramatic cell loss was observed just after deflation of the balloon. At 1h 7±2% of the cells were detected in the heart, 50±4% in the lungs, 21±6% in liver and 3±0.2% in spleen. At 24h the numbers were 4±0.1% (heart), 52±6% (lungs), 23±3% (liver) and 5±2% (spleen). At both times cell persistence was higher after i.m. vs. i.c. injection (1h: P=0.001, 24h: P=0.003). Interestingly, in one animal which was excluded from analysis due to unsuccessful reperfusion, the cardiac cell deposit by i.c. route was approx. twice as high compared to the animals with good reperfusion (14% and 8% at 1h and 24h). Thus, i.m. cardiac cell injection is more effective than i.c. injection, both, immediately and 24h after application. After i.c. application cell persistence seems to be inversely related to coronary flow. In conclusion, if cardiac persistence of cells plays a role for therapeutic benefit of cell therapy, intramyocardial injection may be the superior application technique.