Identifying chronically ischemic dysfunctional or hibernating myocardium is an important clinical endeavor. Patients who are not candidates for CABG or PICA are now being considered for new methods of revascularization such as direct myocardial revascularization with laser channels using catheter based approach (DMR). Electromechanical endocardial (UPV) mapping is used to guide DMR but is not fully validated. Perfusion imaging and dobutamine echocardiography are being used clinically to identify dysfunctional viable myocardium and assess results of novel revascularization techniques. The accuracy of these imaging techniques for these indications have never been fully validated in an animal model. Gold standards for viability used in clinical studies are imperfect. A double ameroid constrictor/swine model for hibernating myocardium shows promise as a good model to compare these technologies against one another and against histopathology and to investigate the efficacy and mechanisms of DMR. In the first aim we propose to use swine models of extensive hibernation and of scar to validate UPV mapping to identify viability vs scar and to compare thallium imaging and dobutamine echocardiography against histopathology to identify viability and sear.
Under aims 2 and 3 the double vessel ameroid model will be used to investigate mechanisms for DMR. The effect of laser therapy on angiogenesis will be assessed using combined morphometric tissue analysis and angiographic techniques. The efficacy of noninvasive imaging (adenosine Tc-99m sestamibilrest Tl-201 and dobutamine echo) to detect neovascularization will be assessed.
In aim 4 radioiodinated MIBG autoradiography will be used to look at the effects of DMR on regional innervation. The results of these experiments should better define the accuracy of methods to image viability and image angiogenesis, and lead to a better understanding of whether DMR revascularizes the heart and whether or not it denervates the heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065395-02
Application #
6537857
Study Section
Diagnostic Imaging Study Section (DMG)
Program Officer
Sopko, George
Project Start
2001-08-01
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$306,559
Indirect Cost
Name
Rhode Island Hospital (Providence, RI)
Department
Type
DUNS #
161202122
City
Providence
State
RI
Country
United States
Zip Code
02903
Johnson, Lynne L; Schofield, Lorraine; Donahay, Tammy et al. (2008) Radiolabeled arginine-glycine-aspartic acid peptides to image angiogenesis in swine model of hibernating myocardium. JACC Cardiovasc Imaging 1:500-10
Thambar, Sukumaran T; Schofield, Lorraine; Poppas, Athena et al. (2003) Validation of R wave voltage endomyocardial mapping to assess myocardial fibrosis: comparison with thallium and dobutamine echocardiography in a swine model. J Interv Cardiol 16:23-31