Angiogenesis and growth factor expression in a model of transmyocardial revascularization

Introduction. The mechanism by which transmyocardial revascularization (TMR) exerts a beneficial effect remains unknown. This thesis hypothesizes that myocardial punctures for TMR cause a myocardial injury, leading to an angiogenic response mediated by a number of growth factors. / Methods. Fifty-three rats underwent ligation of the left coronary artery. Group I (n = 25) served as controls, while Group II (n = 28) underwent concomitant TMR by creating six transmural channels with a 25-gauge needle in the ischemic zone. Surviving animals in both groups were sacrificed at intervals of 1, 2, 4, and 8 weeks (n = 5 in each subgroup). Immunohistochemistry in the infarct areas was performed for factor VIII to assess vascular density. Immunohisto-chemistry using specific antibodies was also performed for transforming growth factor-beta (TGFbeta), basic-fibroblast growth factor (b-FGF), and vasoendothelial growth factor (VEGF). Growth factor expression was quantitated by comparing areas of staining (in mm2) using computerized morphometric analysis. / Results. Mortality was similar in both groups (5/25 vs. 8/28, p = NS). Group II had significantly greater vascular density than Group I (5.65 vs. 4.06 vessels/HPF, p < 0.001), with a peak at 1 week post-operatively (9.12 vs. 5.56 vessels/HPF, p < 0.0001) in both groups. Overall, both TGFbeta and bFGF were significantly higher in the TMR group compared to the control group (0.207 mm2/mm2 vs. 0.141 mm2/mm 2, p < 0.05 and 0.125 mm2/mm2 vs. 0.099 mm2/mm2, p < 0.05). / Conclusions. This model of TMR is associated with a significant angiogenic response, which appears to be mediated by the release of certain angiogenic growth factors such as TGFbeta and bFGF. With the long term patency of laser-created myocardial channels in clinical TMR increasingly in doubt, its mechanism of myocardial revascularization may be similar to that observed in our model.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30723
Date January 2000
CreatorsPelletier, Marc P.
ContributorsChiu, Ray C.-J. (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Division of Surgical Research.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001754441, proquestno: MQ64428, Theses scanned by UMI/ProQuest.

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