Abstract 569: Parathyroid Hormone Reduces LV Perfusion Defects After Myocardial Infarction Quantified by [99mTc]-Sestamibi Pinhole Spect and Promotes Homing of BM-derived Progenitor Cells to the Ischemic Myocardium
Aims: Parathyroid hormone (PTH) was recently shown to effectively induce SC mobilization and to promote cardiac repair after myocardial infarction (MI) by enhanced neovascularization and cell survival. In this study, we non-invasively, repetitively, and quantitatively investigated PTH effects on perfusion by a pinhole single-photon emission computed tomography (SPECT) system and analyzed migration and homing capacity of bone marrow-derived progenitor cells (BMCs) after MI in mice.
Methods: Mice (C57BL/6J) were irradiated, and BM from GFP-transgenic mice was transplanted. Coronary artery ligation was performed 10 weeks later. PTH (80 μg/kg, s.c.) was daily injected for 6 days. Extent of left ventricular (LV) perfusion defects was determined with a [99mTc]-sestamibi triple headed pinhole SPECT system at 6 days (baseline) and 30 days after LAD occlusion. Primary endpoint was change of defect size from baseline to 30 days after MI. Subpopulations of EGFP+ cells in peripheral blood, bone marrow and heart were characterized by flow cytometry. SDF-1α expression was analyzed by ELISA
Results: At baseline mean infarct size was similar in both groups (PTH vs. control). However, change of perfusion defect size was significantly different between PTH (−1,96%±0,86) and control animals (+1,16%±0,87) at day 30. Furthermore, PTH treated animals revealed an enhanced migration of CXCR4+ BMCs associated with an increased expression level of the corresponding growth factor SDF-1α in ischemic myocardium. In contrast, plasma SDF-1α expression was significantly decreased after PTH treatment.
Conclusion: This is the first study demonstrating the suitability of triple headed pinhole SPECT system for repetitive infarct size measurement in mice. In this context, we showed that PTH administration significantly reduced LV perfusion defects associated with SDF-1 driven homing of regenerative CXCR4+ BMCs.