Abstract 18745: Multimodality Molecular Imaging of Inflammation and Cardiac Dysfunction in Pressure-Overload Induced Heart Failure
The role of inflammation in the development and progression of heart failure is increasingly recognized. It may represent a target for therapy, which in turn would benefit from inflammation-targeted imaging. We aimed to characterize a mouse model of transverse aortic constriction (TAC) by magnetic resonance (MR) and positron emission tomography (PET) imaging using 18F-deoxyglucose (FDG). C57Bl/6 mice underwent TAC (n=13) or sham surgery (n=8). MR imaging was conducted at 2d and 8d; FDG images were acquired under ketamine-xylazine (K/X) anesthesia to suppress cardiomyocyte glucose uptake at 3d and 7d. MR images demonstrated rapid and progressive changes in LV geometry and contractile dysfunction, characterized by a marked increase in systolic volume (d8: 47±11 vs 18±3 μL, p<0.001) and decline in ejection fraction vs sham (d8: 38±12 vs 68±3, p<0.001). Despite comparable elevations in blood glucose under K/X, myocardial FDG uptake was markedly elevated in TAC compared to sham (% injected dose(ID)/g; d3: 11±4 vs 4±1; d7: 8±4 vs 3±1, p=0.01). In some TAC mice (n=3/9), cardiomyocyte FDG suppression was successful, with FDG images showing diffuse uptake in the basal LV (%ID/g, d7: 6±2, p<0.05), which may more closely reflect inflammatory cell uptake. Immunostaining identified diffuse CD68-positive macrophages throughout the left ventricle at 9d after TAC surgery. Flow cytometry revealed few CD45-positive leukocytes in the LV, though the number of cells was 3fold higher in TAC vs sham (697±236 vs 256±53 cells/100mg LV tissue). Results suggest that FDG uptake, despite K/X suppression, represents a composite image of diffuse inflammation and altered cardiomyocyte metabolism. Radiotracers with higher specificity for inflammatory cells may be necessary to clearly distinguish inflammation in the setting of TAC. Nevertheless, multimodality imaging may provide insight into the influence of inflammatory cells on LV remodeling and assessment of targeted therapy.
Author Disclosures: J.T. Thackeray: None. K. Hueper: None. M. Gutberlet: None. Y. Wang: None. D. Hartung: None. K.C. Wollert: None. F.M. Bengel: None.
- © 2016 by American Heart Association, Inc.