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

• Document type: Journal article
• Source: JOURNAL OF NUCLEAR CARDIOLOGY; v. N/A, p. 11-pg., 2023-05-10.

Abstract

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)

• FAPESP's process: 17/16450-6 - EFFECTS OF PROLONGED USE OF PENTOXIFILINE OVER MYOCARDIAL PERFUSION CHANGES, ARRYTHMIA EVENTS AND LEFT VENTRICULAR DYSFUNCTION IN THE CHRONIC CHAGAS CARDIOMYOPATHY
• Grantee: Marcus Vinicius Simões
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/25403-9 - Investigations on the pathogenesis, pathophysiology and therapy in humans and in an experimental model with the chronic cardiomyopathy of Chagas Disease
• Grantee: José Antonio Marin-Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/21250-1 - Chronic Chagas Cardiomyopathy in experimental animal model: prospective study of anatomic and functional ventricular changes and the effect of therapeutic interventions
• Grantee: Denise Mayumi Tanaka
• Support Opportunities: Scholarships in Brazil - Post-Doctoral