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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Myocardial 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 results: We 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/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. Conclusions: The 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.

Original languageEnglish
Pages (from-to)2327-2337
Number of pages11
JournalJournal of Nuclear Cardiology
Volume30
Issue number6
DOIs
StatePublished - Dec 2023

Keywords

  • Chronic Chagas cardiomyopathy
  • coronary microcirculation
  • hamsters
  • inflammation
  • ventricular dysfunction

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