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

Session Poster session 5

Speaker Associate Professor Marcus Vinicius Simoes

Event : ESC Congress 2017

  • Topic : imaging
  • Sub-topic : Nuclear Imaging
  • Session type : Poster Session

Authors : D M Tanaka (Ribeirao Preto,BR), E E V Carvalho (Ribeirao Preto,BR), L F L Oliveira (Ribeirao Preto,BR), M M D Romano (Ribeirao Preto,BR), C D Lopes (Ribeirao Preto,BR), A C L Barros-Filho (Ribeirao Preto,BR), F F F Ribeiro (Ribeirao Preto,BR), C G Fabricio (Ribeirao Preto,BR), J Mejia (Ribeirao Preto,BR), L Wichert-Ana (Ribeirao Preto,BR), J S Silva (Ribeirao Preto,BR), A Schmidt (Ribeirao Preto,BR), J A Marin-Neto (Ribeirao Preto,BR), M V Simoes (Ribeirao Preto,BR)

Authors:
D.M. Tanaka1 , E.E.V. Carvalho1 , L.F.L. Oliveira1 , M.M.D. Romano1 , C.D. Lopes1 , A.C.L. Barros-Filho1 , F.F.F. Ribeiro1 , C.G. Fabricio1 , J. Mejia1 , L. Wichert-Ana1 , J.S. Silva1 , A. Schmidt1 , J.A. Marin-Neto1 , M.V. Simoes1 , 1Medical School of Ribeirao Preto, University of Sao Paulo - Ribeirao Preto - Brazil ,

Citation:
European Heart Journal ( 2017 ) 38 ( Supplement ), 895

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.

Results: PD was detected in 18 (60%) of the infected animals. In baseline condition, the CH+DIPY and CH+Saline animals showed larger area of PD (20.9±4.2% and 19.2±5.4, respectively) than CO+DIPY and CO+Saline groups, 3.6±0.9% and 3.8±0.7, respectively, p<0.05. After treatment, there was a significant reduction of the PD only in the CH+DIPY group, 6.7±2.1 (p=0.002), but not in the CH+Saline group (10.5±3.0%) or the CO+DIPI (3.5±0.9%) and CO+Saline (3.9±0.7%), p>0.05. After treatment, CH+DIPY animals exhibited a PD area similar to that of treated control animals (p>0.05). Both infected groups, treated with DIPY or placebo, showed a reduction of LVEF in the post-treatment (53.9±1.5%) when compared to control groups (59.7±2.0%), p=0.02. The histopathological study showed no significant regional coalescent fibrosis in the myocardial segments of infected animals exhibiting PD at baseline. Both infected groups showed greater extent of inflammation (1088.5±83.6 cells/mm2) compared to control groups (329.4±22.8 cells/mm2), p<0.01.

Conclusions: Rest severe myocardial perfusion defects are common in the experimental model of CCC in hamsters, but are not related to regional myocardial fibrosis. The significant reduction of rest PD following prolonged treatment with DIPY suggests that such disturbance is due to microvascular dysfunction caused by the inflammation process.

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