Strain and strain rate correctly identify myocardial dysfunction in advanced glycation end products (AGEs) injected rats

Abstract

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 time, whereas both systolic Scirc/SRcirc were significantly decreased (-16.4 ± 1.8 vs -21.6 ± 2.7% and -4.7 ± 1.0 vs -6.7 ± 0.7 1/s, p<0.05). Myocardial fibrosis was significantly increased compared to BSA-injected animals and was associated with decreased Scirc/SRcirc (figure1).

Conclusion: AGEs injection was associated with prominent cardiac remodelling and increased myocardial fibrosis. STI-derived S/SRcirc correctly detect myocardial dysfunction secondary to increased AGEs and might be useful parameters to monitor the effect of new therapeutic strategies preventing the myocardial dysfunction associated with AGEs.