P4345Severe rest myocardial perfusion defects in experimental chronic Chagas cardiomyopathy correspond to viable hypoperfused myocardium: proof-of-concept study using prolonged dipyridamole administration

Background: Myocardial perfusion disturbance is a common finding in human Chronic Chagas Cardiomyopathy (CCC) but its pathophysiological significance is still unclear. In this study we tested the hypothesis that rest PD may correspond to viable but hypoperfused myocardium that could be reversed by appropriate therapeutic measures. Purpose: We aimed at assessing the effect of the prolonged use of dipyridamole (DIPY), a coronary microvascular dilator and antiplatelet agent, on rest myocardial perfusion in a model of CCC. Methods: We investigated 4 groups of 12-weeks old female hamsters: animals infected with T. cruzi and treated with DIPY (CH+DIPY, n=15), infected and treated with saline (CH+Saline, n=15), non-infected and treated with DIPY (CO+DIPY, n=12), and non-infected treated with saline (CO+Saline, n=11). After 6 months of infection (baseline condition), the animals were submitted to echocardiography and to high-resolution Sestamibi-Tc99m SPECT myocardial perfusion scintigraphy (MPS) imaging. The animals were then treated with DIPY (4 mg/kg by intra-peritoneal injection) twice a day or saline for 4 weeks and then reevaluated using the same imaging methods. These procedures were followed by euthanasia and quantitative histopathological study of fibrosis and inflammation. The extent of resting myocardial perfusion PD was calculated by computing the area of pixels exhibiting <50% radiotracer uptake compared to the maximum pixel value.