Endogenous myocardial angiogenesis and revascularization using a gastric submucosal patch.
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 microm2, 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.
Ruel
Marc A
MA
Center for Minimally Invasive Surgery, Harvard Medical School, Boston, Massachusetts, USA.
Sellke
Frank W
FW
Bianchi
Cesario
C
Khan
Tanveer A
TA
Faro
Renato
R
Zhang
Jian-Ping
JP
Cohn
William E
WE
D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000032:analysis; D003097:Collateral Circulation; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000737:chemistry / Q000473:pathology / Q000502:physiology* / Q000601:surgery; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D015151:Immunoblotting; D007150:Immunohistochemistry; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D013270:Stomach / Q000637:transplantation*; D013524:Surgical Flaps / Q000098:blood supply*; D013552:Swine; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099152:Cadherin 5