Abstract 13391: Comparison of G-CSF and Parathyroid Hormone Treatment After Myocardial Infarction on Cardiac Perfusion Quantified by Pinhole Spect and Stem Cell Homing
Aims: Mobilization of stem cells by G-CSF was shown to have protective effects after myocardial infarction (MI) however clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularisation and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were non-invasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by flow cytometry.
Methods: Mice (C57BL/6J) were infarcted by LAD ligation. PTH (80 μg/kg) and G-CSF (100 μg/kg) were injected for 5 days. After injection of 370 MBq [99mTc]-sestamibi, the extent of left ventricular perfusion defects was determined with a triple headed pinhole clinical SPECT system. Imaging was performed at day 6 and day 30 after LAD occlusion. Defect size was indicated as percentage of left ventricular myocardium. Number of BMCs characterized by Lin-/Sca-1+/c-kit+ cells in peripheral blood and heart was analyzed by FACS.
Results: In contrast to G-CSF-treated and control mice, administration of PTH and the combination of G-CSF and PTH resulted in a significant decrease in absolute infarct size after 30 days. Evaluating change of defect size from day 6 (baseline) to day 30 after MI we found a relative reduction of infarct sizes after cytokine therapy, whereas an increase in perfusion defects (+1.36%) was only found in controls. PTH treatment (−2.64%) and the combination of G-CSF + PTH (−2.80%) showed more pronounced effects in comparison to single G-CSF treatment (−1.41%). Contrary to G-CSF and controls, PTH and the combination showed significant homing of BMCs into ischemic myocardium.
Conclusions: This is the first study, demonstrating the suitability of SPECT as a non-invasive imaging technique for cardiovascular stem cell therapy monitoring in mice. In this context, we showed that PTH administration in contrast to G-CSF significantly reduced LV perfusion defects associated with an enhanced homing of BMCs to the ischemic myocardium.
- © 2010 by American Heart Association, Inc.