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| Tissue Engineered Pro-Angiogenic Fibroblast Matrix Improves Myocardial Perfusion and Function and Limits Ventricular Remodeling following Infarction | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
J. 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
Methods: Lewis rats(n=24) underwent LAD ligation to induce heart failure; experimental animals also underwent application of a 3DFM scaffold to the infarct region. At 4wks, cardiac function was assessed with echocardiography and pressure-volume conductance. Peri-infarct tissue was analyzed for expression of human fibroblast surface protein(HFSP), VEGF, HGF, and the angiogenic mediator NFκβ. Hearts were sectioned for immunofluorescent analysis of angiogenesis by colocalization of platelet endothelial cell adhesion molecule(PECAM) and α smooth muscle actin(αSMA), and digital planimetric analysis of ventricular geometry. Microvascular angiography was performed on a subset of rats with fluorescein-labeled lectin to assess perfusion. Results: See Table. Western blot confirmed presence of HFSP in experimental rats, indicating survival of human cells. VEGF and HGF upregulation in experimental rats confirmed elution by the 3DFM. Angiogenic activation was shown by increased expression of NFκβ. Microvasculature expressing PECAM/αSMA was significantly increased in infarct and borderzones of experimental rats. Microvascular perfusion by lectin angiography was significantly greater in experimental rats in 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). 3DFM rats had increased wall thickness, smaller scar area, shorter scar length, and smaller scar fraction. Cardiac function was preserved in 3DFM rats, with decreased end-systolic volume and increased ejection fraction, fractional shortening, and contractility. Conclusion: Application of an engineered 3DFM augments native angiogenesis through focused delivery of vasculogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse ventricular remodeling, and improves ventricular function.
All values reported as Mean ± SEM. P-Values determined from student t-tests. Borderzone wall thickness, scar area, scar length, and scar fraction were determined by digital planimetric analysis of tissue sections taken from explanted hearts distended at a fixed pressure. End Systolic Volume, Fractional Shortening, and Ejection Fraction were determined by transthoracic echocardiography. Contractility Slope was determined from invasive pressure-volume conductance measurements during IVC occlusion. HFSP - Human Fibroblast Surface Protein; IU - intensity units; VEGF - Vascular Endothelial Growth Factor; HGF - Hepatocyte Growth Factor; NFκβ - Nuclear Factor κβ; PECAM - Platelet Endothelial Cell Adhesion Molecule; αSMA - α Smooth Muscle Actin; Back to 2009 Annual Meeting Back to Program Outline Back to Main Program |
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