Young Investigator Award session - Basic Science: Thursday 4 December 2014, 10:00-11:00 * Location: Agora
D. Schmutzler, E. Khanicheh, L. Xu, M. Mitterhuber, K. Glatz, E. Ellertsdottir, B. Kaufmann, G. Bala, A. Blykers, C. Xavier, K. Gillis, S. Tierens
(+19 others)
2014
European Heart Journal-Cardiovascular Imaging
Purpose: Cardiac tests for diagnosing myocarditis lack sensitivity or specificity. We hypothesized that contrast enhanced ultrasound molecular imaging (CEUMI) could detect endothelial inflammation and the recruitment of specific cellular components of the inflammatory response in murine myocarditis. Methods: Microbubbles (MB) bearing antibodies targeting lymphocyte CD4 (MBCD4), endothelial P-Selectin (MBPSel), MB with a control antibody (MBCtr) and MB with a negative electrical charge for
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... ing of leukocytes (MBN) were prepared. Attachment of MBCD4 was validated in vitro with murine spleen CD4+ lymphocytes. 20 mice were studied after induction of autoimmune myocarditis by immunisation with a-myosinpeptide, 20 mice served as controls. CEUMI of the heart was performed with MBCD4, MBPSel, MBN, and MBCtr. Left ventricular ejection fraction (LVEF) and circumferential strain (CS) were measured. A pathologist blinded to all other data graded the severity of myocarditis on a scale from 0 (no myocarditis) to 4 on histology. Animals were grouped into NM (no myocarditis), MM (moderate myocarditis, score 1-2) and SM (severe myocarditis, score 3-4). Results: In vitro, attachment of MBCD4 to CD4+ lymphocytes was significantly greater than MBCtr (p,0.01). LVEF did not differ between groups (NM 71 + 13%, MM 73 + 7%, SM 62 + 20%, p=0.5), nor did CS (NM 36 + 9%, MM 25 + 11%, SM 30 + 7%, p=0.4). CEUMI (figure) showed increased signal for targeted MB vs MBCtr in MM and SM, whereas signals in NM did not differ from MBCtr. Conclusions: CEUMI can detect endothelial inflammation and leukocyte infiltration in myocarditis, while functional imaging fails to do so. In particular, imaging of CD4+ lymphocytes involved in autoimmune responses in myocarditis is possible. CEUMI may be a powerful method for assessing myocarditis. Purpose: Advanced glycation end products (AGEs) are known to play a key role in the development and progression of cardiovascular diseases, however, the precise underlying mechanism still remains elusive. The study was therefore established to identify the role of AGEs in the pathophysiology of heart failure. Methods: 13 Sprague-Dawley rats underwent a daily injection of 20 mg/kg BSA-modified AGEs (n=9) or control-BSA (n=4) for 6weeks. 2D echo at baseline (BL) and 6w follow-up was used to calculate LV dimensions, volumes (EDV, ESV) and sphericity index (SI). Circumferential strain (Scirc) and strain rate (SRcirc) were obtained at mid-ventricular level using speckle tracking imaging (STI). LV fibrosis was measured using Sirius Red staining. Results: After AGEs injection, a progressive LV remodeling was observed with increased posterior and anterior wall thicknesses, along with higher EDV, ESV and SI compared to BL (0.26 + 0.1mL vs 0.15 + 0.02mL; 0.09 + 0.05mL vs 0.04 + 0.01mL and 0.3 + 0.04 vs 0.18 + 0.03 p,0.05). Ejection fraction and fractional shortening did not change over Abstract 330 Figure. CEUMI in Myocarditis (mean + SEM) Eur Heart J Cardiovasc Imaging Abstracts Supplement,
doi:10.1093/ehjci/jeu250
fatcat:xpjtqwdlvbcqpp3ecryqtw63rq
