Boston - American Association for Thoracic Surgery

89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSL3. Tissue Engineered Pro-Angiogenic Fibroblast Matrix ImprovesMyocardial Perfusion and Function and Limits VentricularRemodeling Following InfarctionJ. Raymond Fitzpatrick, John R. Frederick, Ryan C. McCormick,David A. Harris, Ah-Young Kim, Max J. Smith, Carine M. Laporte,Jeffrey R. Muenzer, Alex J. Gambogi, Y. Joseph Woo *Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania,Philadelphia, PA, USAOBJECTIVE: Microvascular malperfusion after myocardial infarction createsderangements in cardiomyocyte metabolism, causing infarct expansion, adverseremodeling, and functional impairment. Reparative mechanisms exist but areinsufficient to adequately vascularize the myocardium after severe injury. Wehypothesized that a three-dimensional human fibroblast matrix (3DFM), knownto secrete angiogenic cytokines such as vascular endothelial growth factor (VEGF)and hepatocyte growth factor (HGF), would augment native angiogenesis, limitingadverse effects of microvascular dysfunction in ischemic myocardium.METHODS: Lewis rats (n = 24) underwent LAD ligation to induce heart failure;experimental animals also underwent application of a 3DFM scaffold to the infarctregion. At 4 wks, cardiac function was assessed with echocardiography and pressure-volumeconductance. Peri-infarct tissue was analyzed for expression of humanfibroblast surface protein (HFSP), VEGF, HGF, and the angiogenic mediator NFκβ.Hearts were sectioned for immunofluorescent analysis of angiogenesis by colocalizationof platelet endothelial cell adhesion molecule (PECAM) and αsmooth muscleactin (αSMA), and digital planimetric analysis of ventricular geometry. Microvascularangiography was performed on a subset of rats with fluorescein-labeled lectin toassess perfusion.RESULTS: See Table. Western blot confirmed presence of HFSP in experimentalrats, indicating survival of human cells. VEGF and HGF upregulation in experimentalrats confirmed elution by the 3DFM. Angiogenic activation was shown byincreased expression of NFκβ. Microvasculature expressing PECAM/αSMA wassignificantly increased in infarct and borderzones of experimental rats. Microvascularperfusion by lectin angiography was significantly greater in experimental ratsin infarct (1.6 ± 0.2 v 0.4 ± 0.1%, P < 0.01) and borderzones (2.3 ± 0.4 v 0.7 ± 0.2%,P = 0.04), while remote perfusion was equivalent (1.9 ± 0.3 v 2.7 ± 0.4%, P = NS).3 DFM rats had increased wall thickness, smaller scar area, shorter scar length,and smaller scar fraction. Cardiac function was preserved in 3DFM rats, withdecreased end-systolic volume and increased ejection fraction, fractional shortening,and contractility.* AATS Member58