Rest myocardial perfusion disturbance is related to inflammation but not to fibrosis inexperimental chronic chagas cardiomyopathy

Abstract

Purpose: Myocardial perfusion disturbance is a common finding in human chronic Chagas cardiomyopathy (CC), but its underlying tissue changes and pathophysiologic mechanisms are unclear. We aimed at investigating the histologic changes related to the myocardial perfusion changes detected in an experimental model of CC in hamsters. Methods: Female Syrian hamsters (n=34) were infected with 35.000 or 100.000 trypomastigotes forms of T. cruzi Y-strain and were submitted to in vivo imaging 6 to 10 months afterwards. High-resolution rest Sestamibi-Tc-99m-SPECT imaging was used for detection of myocardial perfusion defects (MPD), defined as segments with uptake <50% of the maximum pixel uptake value on polar maps analysis. The segmental and global left ventricular (LV) function was assessed by using 2D-Echocardiogram. Ex vivo histologic analysis included quantitation of fibrosis (picrosirius red) and inflammatory infiltrate. A 13-segment model of LV segmentation was used for all imaging analyses and histologic topographic correlations. Results: MPD were found in 17 (50%) of the infected animals. No transmural scar was detected in segments with MPD. The subgroup of animals with MPD, in comparison to animals without MPD, showed: 1) reduced LV ejection fraction (65±21 and 81±9%, respectively, p<0.01); 2) larger inflammatory infiltrate (172.8±89 and 111.5±54 nuclei/mm2; p=0.04); 3) higher segmental wall motion score (1.44±0.5 and 1.04±0.05%; p=0.003); 4) but similar extent of fibrosis (8.4±3.9; 6.6±3.2%; p=0.06). There was a significant association between regional MPD and abnormal wall motion (p<0,001). The segments with MPD (n=57) as compared to the segments with normal perfusion (n=487) showed larger extent of inflammatory infiltrate (175.8±145.0 and 111.6±69.2 nuclei/mm2, respectively; p=0.001), higher segmental wall motion score (1.65±0.6 and 1.1±0.4; p<0.0001) and comparable extent of fibrosis (10.5±18.6 and 7.4±6.2%; p=0.37). Conclusions: Rest MPD in experimental CC is topographically correlated to inflammatory changes that are intense enough to be associated to wall motion impairment. The fact that these derangements are not due to fibrosis opens the possibility that therapeutic interventions aimed at reducing the degree of myocardial inflammation and/or hypoperfusion may favorably impact on the natural history of this model of experimental CC.