TY - JOUR T1 - <strong>Dissecting the heart/brain interaction in post-infarct myocardial inflammation by whole body translocator protein (TSPO) imaging</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 102 LP - 102 VL - 59 IS - supplement 1 AU - Tobias Borchert AU - Annika Hess AU - Tobias Ross AU - Frank Bengel AU - James Thackeray Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/102.abstract N2 - 102Purpose: Acute myocardial infarction (MI) leads to local and systemic inflammation, which is a determinant of subsequent left ventricular remodeling. Prior work has shown that both acute infarct and chronic remodeling are associated with neuroinflammation. which can be attenuated by angiotensin blockade. We aimed to determine the impact of early anti-inflammatory and/or late anti-remodeling effects of angiotensin convertning enzyme inhibition using TSPO-targeted whole body PET. Methods: C57Bl/6 mice underwent permanent coronary artery ligation (n=30) or sham surgery (n=5). Subgroups of mice were treated with enalapril, either preventatively to attenuate acute inflammation (10d beginning 3d prior to surgery; n=9), or secondarily in the post-inflammatory phase to attenuate remodeling (beginning from 7d post-MI; n=16). Cardiac and neuroinflammation was evaluated using serial whole-body PET and the TSPO-tracer 18F-GE180. Cardiac function and perfusion were assessed by ECG-gated 99mTc-sestamibi SPECT. Results: While preventative enalapril tended to improve 8wk cardiac function compared to untreated MI (%EF, 38±3 vs 50±13, p=0.09), secondary treatment did not (%EF, 45±11, p=0.48). Final infarct size was comparable between groups. Cardiac uptake of 18F-GE180 was elevated 7d post-MI compared to sham (% injected dose (ID)/g, 8.7±1.4 vs 6.3±1, p&lt;0.001). This increase was attenuated by preventative enalapril (7.5±1.1, p=0.03), consistent with acute anti-inflammatory effects. Both preventative enalapril and secondary treatment starting 7 days after MI reduced remote myocardial TSPO upregulation at 8 weeks (untreated: 10.3±2.3, preventative: 7.8±1.6, p=0.021; secondary: 8.2±1.3, p=0.043), suggesting beneficial effects on mitochondrial dysfunction. Overall, brain inflammation was proportional to cardiac TSPO signal (r=0.667, p&lt;0.001), underscoring the tight interaction of these organ systems. While preventative enalapril attenuated brain TSPO signal at 1 wk post-MI (untreated: 2.2±0.3, preventative: 1.8±0.3, p=0.034), neither preventative nor secondary treatment with enalapril affected brain TSPO at 8wk post-MI. Conclusions: Acute post-infarct myocardial inflammation and progressive contractile dysfunction are associated with neuroinflammation. Preventative treatment with enalapril protects the heart and brain from acute inflammation, and lowers cardiac remodeling. The chronic effect of enalapril on neuroinflammation and its importance for development of cognitive impairment require further investigation. ER -