Abstract 1987: Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy
Objective: 7 million Americans suffer from myocardial infarction annually. Post-infarction concerns include progressive ventricular dilatation, decreased function and heart failure. Molecular revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis at the time of infarction offer a potential therapy. EPC migration, vasculogenesis, viability and hemodynamic improvements resulting from this therapy were studied.
Methods: Lewis rats underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections as control. 48 hrs after ligation EPC (CD34+ VEGFR2+ cKit+) upregulation was studied by flow cytometry and immunocytochemistry. 8 wks after ligation, fluorescein conjugated tomato lectin was infused and the hearts explanted for 3D laser confocal angiography. Myocardial viability was quantified by TUNEL labeled apoptosis and myofilament density analysis. Digital planimetry facilitated ventricular geometric assessment. Hemodynamic function was assessed with echocardiography and a pressure-volume (PV) catheter.
Results: SDF/GMCSF therapy upregulated circulating and myocardial EPCs as shown by flow cytometry and immunofluorescence. Borderzone, confocal, microangiographic perfusion increased significantly. Decreased apoptotic fraction and enhanced myofilament density confirmed increased myocardial viability. Planimetric analysis demonstrated preservation of myocardial mass and geometry. Improved hemodynamic function was shown with echocardiography and confirmed with PV analysis.
Conclusion: Neovasculogenic therapy with GMCSF mediated EPC upregulation and SDF mediated EPC chemokinesis is an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.