Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy

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Tanaka, Denise Mayumi ; Fabricio, Camila Godoy ; Marin-Neto, Jose A. ; de Barros Filho, Antonio Carlos Leite ; de Oliveira, Luciano Fonseca Lemos ; Mejia, Jorge ; Almeida, Rafael Ribeiro ; Vieira, Raquel de Souza ; Lopes, Carla Duque ; Batah, Sabrina Setembre ; Moreira, Henrique Turin ; Higuchi, Maria de Lourdes ; Neto, Edecio Cunha ; Fabro, Alexandre Todorovic ; Nekolla, Stephan G. ; Romano, Minna Moreira Dias ; Simoes, Marcus Vinicius

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NUCLEAR CARDIOLOGY; v. N/A, p. 11-pg., 2023-05-10.

Resumo

BackgroundMyocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters.Methods and resultsWe investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 +/- 1.6 to 9.4 +/- 9.7%), but not in CH + PTX (1.9 +/- 3.0% to 2.7 +/- 2.7%) that exhibited MPD area similar to CO (0.0 +/- 0.0% to 0.0 +/- 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 +/- 88.3 cell/mm(2)), as compared to CH + SLN (515.1 +/- 133.0 cell/mm(2)), but larger than CO (193.0 +/- 25.7 cell/mm(2)). The fibrosis and TNF-alpha expression was higher in both infected groups.ConclusionsThe prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC. (AU)

• Processo FAPESP: 17/16450-6 - Efeito do uso prolongado de pentoxifilina sobre as alterações perfusionais miocárdicas, eventos arrítmicos e a evolução da disfunção sistólica ventricular esquerda na cardiomiopatia chagásica crônica
• Beneficiário: Marcus Vinicius Simões
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/25403-9 - Investigações sobre etiopatogenia, fisiopatologia e terapêutica em humanos e em modelo experimental com a cardiomiopatia da Doença de Chagas
• Beneficiário: José Antonio Marin-Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/21250-1 - Cardiomiopatia Chagásica Crônica em modelo experimental animal: estudo prospectivo das alterações anatômicas e funcionais ventriculares e do efeito de intervenções terapêuticas
• Beneficiário: Denise Mayumi Tanaka
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado