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Ann Thorac Surg 2003;75:1443-1449
© 2003 The Society of Thoracic Surgeons
a Center for Minimally Invasive Surgery, Harvard Medical School, Boston, MA, USA
b Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, Boston, MA, USA
Accepted for publication October 24, 2002.
* Address reprint requests to Dr Cohn, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, 110 Francis St, Suite 2A, Boston, MA 02215, USA
e-mail: wcohn{at}caregroup.harvard.edu
BACKGROUND: The gastrointestinal submucosa physiologically produces angiogenic proteins. We examined whether these properties could lead to endogenous myocardial angiogenesis in a swine model of chronic ischemia.
METHODS: Fifteen Yorkshire swine underwent ameroid constrictor placement around the circumflex artery and either lateral epicardial abrasion, creation of a gastroepiploic artery (GEA) based gastric patch, mucosal avulsion, transdiaphragmatic transfer, and apposition of the patch against the circumflex myocardial territory (number = 8; test animals), or lateral epicardial abrasion alone (number = 7; controls). Seven weeks later, lateral myocardial perfusion, endothelial cell density, and expression of VEGFR-1 and VE-cadherin were determined using isotope-labeled microsphere assays, immunohistochemistry, and immunoblotting, respectively.
RESULTS: Microsphere assays showed equivalent lateral/anterior myocardial perfusion indices at rest (1.10 ± 0.49 vs 0.95 ± 0.23, test vs control animals; p = 0.54), but higher perfusion in test animals versus controls during pacing (1.05 ± 0.29 vs 0.69 ± 0.09, test vs controls; p = 0.02). Increased myocardial endothelial cell density (42.6 ± 8.5 vs 26.1 ± 11.6 cells per 3850 µm2, test vs controls; p = 0.02) and expression of VE-cadherin (3.10 ± 0.60-fold change, test vs controls; p = 0.001) were also observed in the lateral territory of test animals versus controls. Reconstitution of the proximally occluded circumflex artery from patch collaterals was demonstrated on gastroepiploic arteriography in a subset of test animals.
CONCLUSIONS: This model results in an angiogenic process of significantly greater magnitude than that resulting from chronic myocardial ischemia alone, without the need for exogenous angiogenic agents.
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