Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 119 | 2024
Research Articles

Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population

Jorge Emilio De All1,2, Juan Francisco Caminos Eguillor3, Simón Marcelo Cohen1, Héctor Freilij4, Arnaldo Dubin2,3,+

1Asociación Cuerpo & Alma, Ciudad Autónoma de Buenos Aires, Argentina
2Sanatorio Otamendi, Ciudad Autónoma de Buenos Aires, Argentina
3Universidad Nacional de La Plata, Facultad de Ciencias Médicas, Cátedras de Farmacología Aplicada y Terapia Intensiva, Provincia de Buenos Aires, Argentina
4Hospital de Niños Ricardo Gutiérrez, Servicio de Parasitología y Enfermedad de Chagas, Ciudad Autónoma de Buenos Aires, Argentina

DOI: 10.1590/0074-02760240018
703 views 1006 downloads
ABSTRACT

BACKGROUND Chagas disease is a systemic illness with widespread microvascular involvement. Experimental and clinical studies suggest that functional and structural microcirculatory abnormalities might be relevant to the disease progression.
OBJECTIVES To show the presence of sublingual microcirculatory alterations in patients with chronic Chagas disease.
METHODS This was a cross-sectional study including adult patients with serologic diagnosis of Chagas disease (n = 41) and control volunteers with negative serology (n = 38), from an endemic rural population. Study participants underwent clinical, electrocardiographic, echocardiographic, and sublingual videomicroscopic assessment. Videos were acquired by a sidestream-dark-field (SDF) imaging device and evaluated by a software-assisted analysis (AVA 3.2 software).
FINDINGS Most of Chagas disease patients were in the indeterminate phase (n = 34) and had lower heart rate and more echocardiographic abnormalities than control group (50 vs. 26%, p = 0.03). They also exhibited higher small microvessels total and perfused vascular density (20.12 ± 2.33 vs. 19.05 ± 2.25 and 20.03 ± 2.28 vs. 19.01 ± 2.25 mm/mm2, p < 0.05 for both). Other microvascular variables did not differ between groups.
MAIN CONCLUSIONS Patients with chronic Chagas disease exhibited increases in sublingual total and perfused microvascular density. Angiogenesis might be the underlying mechanism. The videomicroscopic assessment of mucosal sublingual microcirculation might be an additional tool in the monitoring of Chagas disease.

REFERENCES
01. WHO - World Health Organization. Chagas disease (American trypanosomiasis). 2024. Available from: https://www.who.int/ health-topics/chagas-disease#tab=tab_1.
02. Dias E, Laranja FS, Miranda A, Nobrega G. Chagas’ disease: a clinical, epidemiologic, and pathologic study. Circulation. 1956; 14(6): 1035-60.
03. Rojo G, Pèlissier F, Sandoval-Rodriguez A, Bacigalupo A, García V, Pinto R, et al. Organs infected with Trypanosoma cruzi and DTU identification in the naturally infected rodent Octodon degus. Exp Parasitol. 2020; 215: 107931.
04. Barbosa Jr AA, Andrade ZA. Identificação do Trypanosoma cruzi nos tecidos extracardíacos de portadores de miocardite crônica chagásica. Rev Soc Bras Med Trop. 1984; 17: 123-6.
05. Macaluso G, Grippi F, Di Bella S, Blanda V, Gucciardi F, Torina A, et al. A Review on the immunological response against Trypanosoma cruzi. Pathogens. 2023; 12(2): 282.
06. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation. 2007; 115(9): 1109-23.
07. Nisimura LM, Estato V, de Souza EM, Reis PA, Lessa MA, Castro- Faria-Neto HC, et al. Acute Chagas disease induces cerebral microvasculopathy in mice. PLoS Negl Trop Dis. 2014; 8(7): e2998.
08. Tanowitz HB, Kaul DK, Chen B, Morris SA, Factor SM, Weiss LM, et al. Compromised microcirculation in acute murine Trypanosoma cruzi infection. J Parasitol. 1996; 82(1): 124-30.
09. Nisimura LM, Ferreira RR, Coelho LL, Souza EM, Gonzaga BM, Ferrão PM, et al. Increased angiogenesis parallels cardiac tissue remodelling in experimental acute Trypanosoma cruzi infection. Mem Inst Oswaldo Cruz. 2022; 117: e220005.
10. Vellasco L, Svensjö E, Bulant CA, Blanco PJ, Nogueira F, Domont G, et al. Sheltered in stromal tissue cells, Trypanosoma cruzi orchestrates inflammatory neovascularization via activation of the mast cell chymase pathway. Pathogens. 2022; 11(2): 187.
11. Pereira SAL, Severino VO, Kohl NL, Rodrigues DB, Alves PM, Clemente-Napimoga JT, et al. Expression of cytokines and chemokines and microvasculature alterations of the tongue from patients with chronic Chagas’ disease. Parasitol Res. 2009; 105(4): 1031-9.
12. Dubin A, Kanoore Edul VS, Eguillor JFC, Ferrara G. Monitoring microcirculation: utility and barriers - A point-of-view review. Vasc Health Risk Manag. 2020; 16: 577-89.
13. Sartor P, Colaianni I, Cardinal MV, Bua J, Freilij H, Gürtler RE. Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation. PLoS Negl Trop Dis. 2017; 11(2): e0005336.
14. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015; 28(1): 1-39.e14.
15. Saraiva RM, Mediano MFF, Mendes FS, Sperandio da Silva GM, Veloso HH, Sangenis LHC, et al. Chagas heart disease: an overview of diagnosis, manifestations, treatment, and care. World J Cardiol. 2021; 13(12): 654-75.
16. Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C. Sidestream dark field (SDF) imaging: a novel stroboscopic LED ringbased imaging modality for clinical assessment of the microcirculation. Opt Express. 2007; 15(23): 15101-14.
17. Pozo MO, Kanoore Edul VS, Ince C, Dubin A. Comparison of different methods for the calculation of the microvascular flow index. Crit Care Res Pract. 2012; 2012: 102483.
18. Dobbe JG, Streekstra GJ, Atasever B, van Zijderveld R, Ince C. Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis. Med Biol Eng Comput. 2008; 46(7): 659-70.
19. Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med. 2007; 49(1): 88-98, 98.e1-2.
20. Kanoore Edul VS, Ince C, Estenssoro E, Ferrara G, Arzani Y, Salvatori C, et al. The effects of arterial hypertension and age on the sublingual microcirculation of healthy volunteers and outpatients with cardiovascular risk factors. Microcirculation. 2015; 22(6): 485-92.
21. Gonzaga BMS, Horita SIM, Beghini DG, Gomes F, Nisimura LM, Dos Santos IB, et al. Effect of benznidazole on cerebral microcirculation during acute Trypanosoma cruzi infection in mice. Sci Rep. 2022; 12(1): 21048.
22. Ferreira CS, Lopes ER, Chapadeiro E, Almeida HO, de Souza WF, da Silva Neto IJ. Post-mortem coronary angiography in chronic Chagas carditis, Anatomo-radiologic correlation. Arq Bras Cardiol. 1980; 34(2): 81-6.
23. Guedes-da-Silva FH, Shrestha D, Salles BC, Figueiredo VP, Lopes LR, Dias L, et al. Trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model. Microvasc Res. 2015; 97: 130-6.
24. Penas FN, Carta D, Dmytrenko G, Mirkin GA, Modenutti CP, Cevey ÁC, et al. Treatment with a new peroxisome proliferatoractivated receptor gamma agonist, pyridinecarboxylic acid derivative, increases angiogenesis and reduces inflammatory mediators in the heart of Trypanosoma cruzi-infected mice. Front Immunol. 2017; 8: 1738.
25. Higuchi ML, Fukasawa S, De Brito T, Parzianello LC, Bellotti G, Ramires JA. Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas’ disease: a three dimensional confocal microscopy study. Heart. 1999; 82(3): 279-85.
26. Ferreira V, Molina MC, Schwaeble W, Lemus D, Ferreira A. Does Trypanosoma cruzi calreticulin modulate the complement system and angiogenesis? Trends Parasitol. 2005; 21(4): 169-74.
27. Beghini M, Abdalla DR, Olegario JGP, Furtado TCS, de Faria JB, Rodrigues DBR et al. Immunohistological insight into the correlation between cardiac and lingual musculature in chronic chagas disease. Res Soc Dev. 2022; 11(5): e58211528156.
28. Ntellas P, Perivoliotis K, Dadouli K, Koukoulis GK, Ioannou M. Microvessel density as a surrogate prognostic marker in patients with multiple myeloma: a meta-analysis. Acta Haematol. 2017; 138(2): 77-84.
29. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991; 324(1): 1-8.
30. Pruneri G, Ponzoni M, Ferreri AJ, Decarli N, Tresoldi M, Raggi F, et al. Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol. 2002; 118(3): 817-20.
31. Bulant CA, Blanco PJ, Müller LO, Scharfstein J, Svensjö E. Computer- aided quantification of microvascular networks: application to alterations due to pathological angiogenesis in the hamster. Microvasc Res. 2017; 112: 53-64.
32. Hilty MP, Merz TM, Hefti U, Ince C, Maggiorini M, Hefti JP. Recruitment of non-perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m. J Physiol. 2019; 597(10): 2623-38.
33. Dubin A, Henriquez E, Hernández G. Monitoring peripheral perfusion and microcirculation. Curr Opin Crit Care. 2018; 24(3): 173-80.
34. Borges JP, Mendes FSNS, Rangel MVDS, Lopes GO, da Silva GMS, da Silva PS, et al. Exercise training improves microvascular function in patients with Chagas heart disease: Data from the PEACH study. Microvasc Res. 2021; 134: 104106.
35. Barata Kasal DA, Britto A, Verri V, De Lorenzo A, Tibirica E. Systemic microvascular endothelial dysfunction is associated with left ventricular ejection fraction reduction in chronic Chagas disease patients. Microcirculation. 2021; 28(2): e12664.
36. Borges JP, Mendes FSNS, Lopes GO, Sousa AS, Mediano MFF, Tibiriçá E. Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy? Int J Cardiol. 2018; 265: 35-7.
37. Uz Z, van Gulik TM, Aydemirli MD, Guerci P, Ince Y, Cuppen D, et al. Identification and quantification of human microcirculatory leukocytes using handheld video microscopes at the bedside. J Appl Physiol. 2018; 124(6): 1550-7.

Financial support: Asociación Cuerpo & Alma, Sanatorio Otamendi.
+ Corresponding author: arnaldodubin@gmail.com
ORCID https://orcid.org/0000-0002-3349-5447
Received 22 January 2024
Accepted 12 June 2024

HOW TO CITE
De All JE, Caminos Eguillor JF, Cohen SM, Freilij H, Dubin A. Sublingual microcirculatory alterations in Chagas disease: an observational study in an endemic rural population. Mem Inst Oswaldo Cruz. 2024; 119: e240018.

Our Location

Memórias do Instituto Oswaldo Cruz

Av. Brasil 4365, Castelo Mourisco 
sala 201, Manguinhos, 21040-900 
Rio de Janeiro, RJ, Brazil

Tel.: +55-21-2562-1222

This email address is being protected from spambots. You need JavaScript enabled to view it.

Support Program

logo iocb

logo governo federal03h 
faperj   cnpq capes