Hybrid Surgical Angiogenesis: Omentopexy Can Enhance Myocardial Angiogenesis Induced by Cell Therapy

Abstract

The conditions at the injection site are important in cell transplantation for severe ischemic heart disease. The omentum is both a well-vascularized tissue and a source of angiogenic factors. We examined the effectiveness of autologous bone marrow-derived mononuclear cells (BM-MNCs) with or without omentopexy in a large animal model. Myocardial infarction was generated in the lateral wall by ligation of coronary artery branches in miniswine. Animals received BM-MNC injection with or without omentopexy. Controls received saline only. Three weeks after surgery, regional myocardial blood flow and contractility were measured, and density of arterioles was evaluated immunohistologically. Angiography and postmortem examinations were performed to determine collateral communication. Regional myocardial contractility was significantly improved by BM-MNC transplantation both with and without omentopexy (0.29 +/- 0.02 vs 0.11 +/- 0.03, p < 0.01, 0.30 +/- 0.02 vs 0.12 +/- 0.01, p < 0.01, respectively). Relative regional myocardial blood flow in the combined omentopexy group was significantly higher than the controls both at rest (1.05 +/- 0.11 vs 0.57 +/- 0.07, p < 0.01) and under stress (1.09 +/- 0.08 vs 0.40 +/- 0.10, p < 0.01). The number of arterioles (< 50 microm) in both groups were higher than the controls (88.1 +/- 5.00 vs 38.1 +/- 8.99, p < 0.01 and 109.2 +/- 9.91 vs 38.1 +/- 8.99, p < 0.01, respectively). The number of large arterioles (> 50 microm) in the combined omentopexy group was significantly higher than in both BM-MNC alone (26.9 +/- 2.4 vs 17.6 +/- 1.8, p = 0.011) and controls (26.9 +/- 2.4 vs 10.0 +/- 1.3, p < 0.01). Collateral communication between the omentum and myocardium was demonstrated by angiography and postmortem injection. The BM-MNC transplantation may attenuate cardiac contractile dysfunction, and omentopexy may enhance angiogenesis induced by BM-MNC transplantation.