Laser Induced Myocardial Angiogenesis

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DESCRIPTION (Provided by Applicant): There are an increasing number of patients with disabling angina as a result ot end-stage coronary artery disease. Transmyocardial laser revascularization (TMR) was developed to provide an option for these patients. who are not amenable to conventional methods of revascularization. Clinically, TMR successfully reduces anginal symptoms and improves the quality of the patient's life. The exact mechanism whereby TMR achieves these results is unclear. The objective of this study is to investigate the importance of angiogenesis as a mechanism of TMR. Specifically to determine if there is an upregulation of angiogenic growth factors after TMR. With more endogenous production of angiogens, new blood vessels should develop, perfusion increase and function improve. The potential synergistic response to the addition of exogenous angiogenic growth factors in combination with TMR will be examined. Variations in the response due to different wavelengths of laser light and differences in tissue penetration of this light will be studied. An established animal model of chronic myocardial ischemia will be employed. The angiogenic response will be assessed: 1.) on a molecular basis by demonstrating an increase in the mRNA for bFGF and VEGF; 2.) histologically by an increase in new blood vessels. Perfusion changes will be assessed by colored microspheres and perfusion MRI. Functional changes will be monitored by stress echocardiography and cine MRI. Further enhancement of the angiogenic response will be achieved by the intramyocardial addition of bFGF protein and by VEGF delivered via an adenoviral mediated gene transfer. Finally the differences in TMR by infrared light (carbon dioxide) versus ultraviolet light (excimer) will be assessed. While the clinical results are encouraging, better understanding of the mechanisms of TMR will lead to better treatment for these patients.