Abstract 14273: Effective Retention and Distribution of a Collagen Matrix Injected into the Infarcted Mouse Heart Limits Loss of Cardiac Function
Background: Little is known regarding the retention and distribution properties of injectable hydrogels being investigated for cardiac applications. Here we used imaging methods to evaluate the delivery of a collagen matrix injected as treatment for myocardial infarction (MI).
Methods/Results: C57BL/6J mice underwent LAD ligation to induce MI. At 1wk post-MI, mice received myocardial injections of PBS or collagen matrix (50μl). The matrix was labeled with hexadedecyl-4-[18F]fluorobenzoate (18F-HFB) or quantum dots (q-dots) to assess its retention and distribution by positron emission tomography (PET) and immunofluorescence imaging, respectively. In vitro 18F-HFB labeling efficiency was 81.6±1.9%. For PET, mice were co-injected with 18F-NaF to demarcate the skeleton (for image co-registration) and with 13N-NH3 to delineate the infarct. Scans of 18F-HFB-labeled matrix were performed 10min and 2h after injection. PET images showed that the collagen matrix at 10min re-distributed evenly within the ischemic territory by 2h. Activity in the myocardium was 70.4±3.1% at 10min and 62.5±4.6% at 2h. Ex vivo biodistribution revealed greater matrix retention in the myocardium (66.2±1.5%) compared to other tissues (p<0.001). For covalently linked q-dots, labeling efficiency was 96.1±1.6%. Bioluminescence imaging of the heart showed that 84.1±7.4% of the injected matrix was retained in the myocardium. Left ventricular ejection fraction (LVEF) as measured by echocardiography, was reduced from 1wk to 4wk post-MI with PBS treatment (37.8±3.2% to 27.0±2.3%), whereas it was preserved in the matrix group (36.6±3.0% to 38.2±3.6%). At 4wk, LVEF was greater in matrix treated hearts compared to PBS (p=0.02). Also, arteriole density was higher in the matrix group (5.5±0.5 /field of view (FOV)) vs. PBS (3.0±0.6/FOV; p=0.007), and the infarct wall thickness was increased (25.1±1.5%) vs. PBS (15.3±1.1%; p<0.001).
Conclusion: The collagen matrix was retained upon injection to the MI heart and spread within the ischemic tissue. The matrix maintains a higher arteriole density and LV mass, and limits the loss of cardiac function. This study establishes the suitability of our collagen matrix as an injectable therapy for application in the heart following infarction.
- © 2013 by American Heart Association, Inc.