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

  • ORIGINAL ARTICLE
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Journal of Nuclear Cardiology Aims and scope

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.

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Abbreviations

CCC:

Chronic Chagas’ cardiomyopathy

MPD:

Myocardial perfusion defect

PTX:

Pentoxifylline

PLB:

Placebo

LV:

Left ventricle

LVEDD:

Left ventricle end diastolic dimension

LVESD:

Left ventricle end systolic dimension

LVEF:

Left ventricular ejection function

SPECT:

Single-photon emission computerized tomography

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Funding

This study was supported by a research grant from Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP – Process: 2017/16450-6, 2016/25403-9 and 2019/21250-1) and Fundação de Apoio ao Ensino Pesquisa e Assistência do Hospital das Clínicas (FAEPA).

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Authors and Affiliations

  1. Medical School of Ribeirao Preto, University of São Paulo, Sao Paulo, Brazil

    Denise Mayumi Tanaka PhD, Camila Godoy Fabricio MS, José A. Marin-Neto PhD, Antônio Carlos Leite de Barros Filho MS, Carla Duque Lopes PhD, Sabrina Setembre Batah MS, Henrique Turin Moreira PhD, Alexandre Todorovic Fabro PhD, Minna Moreira Dias Romano PhD & Marcus Vinícius Simões PhD

  2. Department of Applied Physical Therapy, Institute of Health Sciences, Federal University of Triangulo Mineiro, Uberaba, Brazil

    Luciano Fonseca Lemos de Oliveira PhD

  3. Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    Jorge Mejia PhD

  4. Faculty of Medicine, Heart Institute (InCor), University of Sao Paulo, Sao Paulo, Brazil

    Rafael Ribeiro Almeida PhD, Raquel de Souza Vieira MS, Maria de Lourdes Higuchi PhD & Edecio Cunha Neto PhD

  5. Department of Nuclear Medicine at Technische Universität, Munich, Germany

    Stephan G. Nekolla PhD

  6. Cardiology Division, Internal Medicine Department, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, 3900 Bandeirantes Avenue, Ribeirão Preto, São Paulo, 14048900, Brazil

    Marcus Vinícius Simões PhD

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  1. Denise Mayumi Tanaka PhD
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Correspondence to Marcus Vinícius Simões PhD.

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Tanaka, D.M., Fabricio, C.G., Marin-Neto, J.A. et al. Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas’ cardiomyopathy. J. Nucl. Cardiol. 30, 2327–2337 (2023). https://doi.org/10.1007/s12350-023-03270-y

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