Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy

PurposePost-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.ProceduresLewis rats (n = 91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation.FindingsSDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12 ± 0.02% vs. 0.06 ± 0.01% circulating lymphocytes, p = 0.005), 48 hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02 ± 1.7 × 10−2 μm3 blood/μm3 myocardial tissue vs. 2.03 ± 0.7 10−2 μm3 blood/μm3 myocardial tissue, p = 0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98 ± 0.09 mm vs. 0.67 ± 0.06 mm, p = 0.003) and ventricular diameter (7.81 ± 0.99 mm vs. 9.41 ± 1.1 mm, p = 0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4 ± 18.1% vs. 25.3 ± 15.6%, p = 0.001; pre-load adjusted maximal power: 6.6 ± 2.6 mW/μl2 vs. 2.7 ± 1.4 mW/μl2, p = 0.01).ConclusionNeovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.