Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy

Purpose: Post-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-1 alpha (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated. Procedures: Lewis 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. Findings: SDF/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 x 10(-2) mu m(3) blood/mu m(3) myocardial tissue vs. 2.03 +/- 0.710(-2) mu m(3) blood/mu m(3) 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 +/- 1 15.6%, p = 0.001; pre-load adjusted maximal power: 6.6 +/- 2.6 mW/mu l(2) vs. 2.7 +/- 1.4 mW/mu l(2), p = 0.01). Conclusion: Neovasculogenic 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. (Heart, Lung and Circulation 2010;19:644-654) (C) 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.