| | | Document Type | : | Latin Dissertation | | Language of Document | : | English | | Record Number | : | 55492 | | Doc. No | : | TL25446 | | Call number | : | 3268221 | | Main Entry | : | Bin Wang | | Title & Author | : | Oxygen delivery and angiogenesis post-myocardial infarctionBin Wang | | College | : | Temple University | | Date | : | 2007 | | Degree | : | Ph.D. | | student score | : | 2007 | | Page No | : | 162 | | Abstract | : | We have developed a series of novel techniques, adapted from the field of tumor biology, to quantify vascular structure and function and to explore the role of Angiotensin (Ang) II receptor AT1 in cardiac remodeling post myocardial infarction (MI). We examined the scar neovasculature at 1-4 weeks post-MI in Sprague-Dawley rats with a view towards its ability to deliver and exchange oxygen. We compared untreated controls with rats treated with losartan, an AT1 receptor antagonist. Our findings indicate that at the infarct site there is significant decrease in the number of anatomical vessels and perfused vessels compared to controls. These changes are accompanied by progressive increases in diffusion distance and tissue hypoxia (100% increases in EF5/Cy3 staining at 4 weeks post-MI). Losartan treated rats exhibited a significantly less marked reduction in vascular perfusion and significantly lesser extent of tissue hypoxia. These findings implicate AT1 receptor upregulation, and perhaps angiotensin related peptides, as being antiangiogenic. We have also developed an anatomically realistic mathematical model of oxygen transport in cardiac tissue to help in deciding what angiogenic strategies should be used to rebuild the vasculature post-MI. Model predictions closely match our experimental measurements and can be used to predict distributions of oxygen concentration in normal and infarcted rat hearts. Furthermore, the model can accurately predict tissue oxygen levels in infarcted tissue treated with pro-angiogenic compounds. We have identified the effects of an angiogenic therapy on MI rats. In this study MI rats were treated by systemic administration of rhVEGF 165. Perfusion, oxygenation, and cardiac function of treated MI rats were measured and compared with untreated MI rats. Our findings indicate that systemic rhVEGF165 treatment does not improve the function of the infarcted heart as measured by echocardiography, but does significantly improve vascularity and oxygenation. Overall, our findings indicate that systemic rhVEGF165 therapy enhances vascular density and oxygenation in MI region, but does not lead to improvements in cardiac function. In the future, we will selectively deliver rhVEGF165 to MI region using the targeted drug delivery system developed in our laboratory and evaluate the therapeutical effects using the techniques developed in this project. | | Subject | : | Applied sciences; Angiogenesis; Myocardial infarction; Oxygen delivery; Biomedical research; 0541:Biomedical research | | Added Entry | : | M. F. Kiani | | Added Entry | : | Temple University |
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