Abstract 13494: Histopathological Analysis Indicates a Significant Role of Myocardial Perfusion Disturbance in Tissue Lesion in Chronic Chagas’ Cardiomyopathy Experimental Model

Abstract

Introduction: Coronary microvascular perfusion disturbance (MPD) is frequently found in Chronic Chagas' cardiomyopathy (CCC), but its role in tissue lesion and left ventricular dysfunction progression is still unclear. Hypothesis: As MPD is associated with more severe subendocardial myocardial injury, we tested the hypothesis that histopathological changes in subendocardial layer could be quantitatively correlated to MPD in experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n=23) infected with 3.5x10 4 blood trypomastigote forms of T. cruzi ( Y strain ) and their respective controls (n=6) were studied. At 8 months after infection, the animals underwent in vivo high-resolution myocardial rest perfusion scintigraphy with 99m Tc-Sestamibi and transthoracic echocardiography. After euthanasia, the myocardial tissue was processed for quantitative histopathological analysis of mononuclear infiltrate index (MII) using hematoxylin-eosin staining and myocardial fibrosis using picrosirius staining in LV wall layers: subendocardium, mesocardium and subepicardium. Results: Fourteen animals (61%) presented rest MPD. The area of MPD was negatively correlated with LVEF (R=-0.5; p=0.02), and positively correlated with LV diastolic diameter (R=0.83; p<0.01). Animals with MPD exhibited increased extent of myocardial fibrosis in the subendocardial layer (0.67 + 0.18%) as compared to control animals (0.47 + 0.15%), p=0.03. However, the extent of total transmural fibrosis or fibrosis in other myocardial layers were similar among groups. The group with MPD presented higher values of MII in every myocardial layer as compared to controls and animals without MPD. However, only the MII in the subendocardial layer presented positive correlation with the extent of rest MPD (R=0.55, p=0.001). Conclusions: Our results indicate that MPD is significantly correlated with histopathological changes located in the subendocardial layer of LV walls. These results suggest that MPD may act as an amplifying and localizing factor for inflammation and fibrosis, suggesting a relevant role for myocardial hypoperfusion in the mechanisms of myocardial injury in CCC.