1921
Volume 94, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

Chagas disease, caused by the triatominae , is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20–30% of infected people 10–40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K current and L-type Ca current at 30 and 90 dpi. Taking together, our results demonstrate that infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.15-0255
2016-05-04
2018-12-16
Loading full text...

Full text loading...

/deliver/fulltext/14761645/94/5/1028.html?itemId=/content/journals/10.4269/ajtmh.15-0255&mimeType=html&fmt=ahah

References

  1. WHO, 2010. Factsheet on Chagas Disease. Geneva, Switzerland: World Health Organization. [Google Scholar]
  2. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV, , 2007. Pathogenesis of chronic Chagas heart disease. Circulation 115: 11091123.[Crossref] [Google Scholar]
  3. Dias E, Laranja FS, Miranda A, Nobrega G, , 1956. Chagas' disease: a clinical, epidemiologic, and pathologic study. Circulation 14: 10351060.[Crossref] [Google Scholar]
  4. Tostes S, Jr Bertulucci Rocha-Rodrigues D, de Araujo Pereira G, Rodrigues V, Jr, 2005. Myocardiocyte apoptosis in heart failure in chronic Chagas' disease. Int J Cardiol 99: 233237.[Crossref] [Google Scholar]
  5. Kumar R, Kline IK, Abelmann WH, , 1969. Experimental Trypanosoma cruzi myocarditis: relative effects upon the right and left ventricles. Am J Pathol 57: 3148. [Google Scholar]
  6. Wen JJ, Vyatkina G, Garg N, , 2004. Oxidative damage during chagasic cardiomyopathy development: role of mitochondrial oxidant release and inefficient antioxidant defense. Free Radic Biol Med 37: 18211833.[Crossref] [Google Scholar]
  7. Vyatkina G, Bhatia V, Gerstner A, Papaconstantinou J, Garg N, , 2004. Impaired mitochondrial respiratory chain and bioenergetics during chagasic cardiomyopathy development. Biochim Biophys Acta 1689: 162173.[Crossref] [Google Scholar]
  8. Roman-Campos D, Duarte HL, Sales PA, Jr Natali AJ, Ropert C, Gazzinelli RT, Cruz JS, , 2009. Changes in cellular contractility and cytokines profile during Trypanosoma cruzi infection in mice. Basic Res Cardiol 104: 238246.[Crossref] [Google Scholar]
  9. Roman-Campos D, Sales-Junior P, Duarte HL, Gomes ER, Lara A, Campos P, Rocha NN, Resende RR, Ferreira A, Guatimosim S, Gazzinelli RT, Ropert C, Cruz JS, , 2013. Novel insights into the development of chagasic cardiomyopathy: role of PI3Kinase/NO axis. Int J Cardiol 167: 30113020.[Crossref] [Google Scholar]
  10. Roman-Campos D, Sales-Junior P, Duarte HL, Gomes ER, Guatimosim S, Ropert C, Gazzinelli RT, Cruz JS, , 2013. Cardiomyocyte dysfunction during the chronic phase of Chagas disease. Mem Inst Oswaldo Cruz 108: 243245.[Crossref] [Google Scholar]
  11. Cunha-Neto E, Bilate AM, Hyland KV, Fonseca SG, Kalil J, Engman DM, , 2006. Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39: 4154.[Crossref] [Google Scholar]
  12. Pereira Barretto AC, Mady C, Arteaga-Fernandez E, Stolf N, Lopes EA, Higuchi ML, Bellotti G, Pileggi F, , 1986. Right ventricular endomyocardial biopsy in chronic Chagas' disease. Am Heart J 111: 307312.[Crossref] [Google Scholar]
  13. Carrasco HA, Medina M, Inglessis G, Fuenmayor A, Molina C, Davila D, , 1983. Right ventricular function in Chagas disease. Int J Cardiol 2: 325338.[Crossref] [Google Scholar]
  14. Marin-Neto JA, Marzullo P, Sousa AC, Marcassa C, Maciel BC, Iazigi N, L'Abbate A, , 1988. Radionuclide angiographic evidence for early predominant right ventricular involvement in patients with Chagas' disease. Can J Cardiol 4: 231236. [Google Scholar]
  15. Nunes M do C, Barbosa M de M, Brum VA, Rocha MO, , 2004. Morphofunctional characteristics of the right ventricle in Chagas' dilated cardiomyopathy. Int J Cardiol 94: 7985.[Crossref] [Google Scholar]
  16. Chen G, Barr S, Walsh D, Rohde S, Brewer A, Bilezikian JP, Wittner M, Tanowitz HB, Morris SA, , 1996. Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease. J Mol Cell Cardiol 28: 931941.[Crossref] [Google Scholar]
  17. Souza AP, Jelicks LA, Tanowitz HB, Olivieri BP, Medeiros MM, Oliveira GM, Pires AR, Santos AM, Araujo-Jorge TC, , 2010. The benefits of using selenium in the treatment of Chagas disease: prevention of right ventricle chamber dilatation and reversion of Trypanosoma cruzi-induced acute and chronic cardiomyopathy in mice. Mem Inst Oswaldo Cruz 105: 746751.[Crossref] [Google Scholar]
  18. Federici EE, Abelmann WH, Neva FA, , 1964. Chronic and progressive myocarditis and myositis in C3h mice infected with Trypanosoma cruzi . Am J Trop Med Hyg 13: 272280. [Google Scholar]
  19. Junquiera LC, Junqueira LC, Brentani RR, , 1979. A simple and sensitive method for the quantitative estimation of collagen. Anal Biochem 94: 9699.[Crossref] [Google Scholar]
  20. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ, , 1981. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391: 85100.[Crossref] [Google Scholar]
  21. Roman-Campos D, Duarte HL, Gomes ER, Castro CH, Guatimosim S, Natali AJ, Almeida AP, Pesquero JB, Pesquero JL, Cruz JS, , 2010. Investigation of the cardiomyocyte dysfunction in bradykinin type 2 receptor knockout mice. Life Sci 87: 715723.[Crossref] [Google Scholar]
  22. Prado CM, Celes MR, Malvestio LM, Campos EC, Silva JS, Jelicks LA, Tanowitz HB, Rossi MA, , 2012. Early dystrophin disruption in the pathogenesis of experimental chronic Chagas cardiomyopathy. Microbes Infect 14: 5968.[Crossref] [Google Scholar]
  23. Jelicks LA, Shirani J, Wittner M, Chandra M, Weiss LM, Factor SM, Bekirov I, Braunstein VL, Chan J, Huang H, Tanowitz HB, , 1999. Application of cardiac gated magnetic resonance imaging in murine Chagas' disease. Am J Trop Med Hyg 61: 207214. [Google Scholar]
  24. Chandra M, Tanowitz HB, Petkova SB, Huang H, Weiss LM, Wittner M, Factor SM, Shtutin V, Jelicks LA, Chan J, Shirani J, , 2002. Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain). Int J Parasitol 32: 897905.[Crossref] [Google Scholar]
  25. Nerbonne JM, Kass RS, , 2005. Molecular physiology of cardiac repolarization. Physiol Rev 85: 12051253.[Crossref] [Google Scholar]
  26. Xu H, Guo W, Nerbonne JM, , 1999. Four kinetically distinct depolarization-activated K+ currents in adult mouse ventricular myocytes. J Gen Physiol 113: 661678.[Crossref] [Google Scholar]
  27. Bers DM, , 2008. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 70: 2349.[Crossref] [Google Scholar]
  28. Ribeiro AL, Marcolino MS, Prineas RJ, Lima-Costa MF, , 2014. Electrocardiographic abnormalities in elderly Chagas disease patients: 10-year follow-up of the Bambui Cohort Study of Aging. J Am Heart Assoc 3: e000632.[Crossref] [Google Scholar]
  29. Nunes M do C, Rocha MO, Ribeiro AL, Colosimo EA, Rezende RA, Carmo GA, Barbosa MM, , 2008. Right ventricular dysfunction is an independent predictor of survival in patients with dilated chronic Chagas' cardiomyopathy. Int J Cardiol 127: 372379.[Crossref] [Google Scholar]
  30. Caldas S, Caldas IS, Diniz L de F, Lima WG, Oliveira R de P, Cecilio AB, Ribeiro I, Talvani A, Bahia MT, , 2012. Real-time PCR strategy for parasite quantification in blood and tissue samples of experimental Trypanosoma cruzi infection. Acta Trop 123: 170177.[Crossref] [Google Scholar]
  31. Marcon GE, de Albuquerque DM, Batista AM, Andrade PD, Almeida EA, Guariento ME, Teixeira MA, Costa SC, , 2011. Trypanosoma cruzi: parasite persistence in tissues in chronic chagasic Brazilian patients. Mem Inst Oswaldo Cruz 106: 8591.[Crossref] [Google Scholar]
  32. Andrade SG, , 1990. Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice. Mem Inst Oswaldo Cruz 85: 1727.[Crossref] [Google Scholar]
  33. Fernandez-Velasco M, Ruiz-Hurtado G, Hurtado O, Moro MA, Delgado C, , 2007. TNF-alpha downregulates transient outward potassium current in rat ventricular myocytes through iNOS overexpression and oxidant species generation. Am J Physiol Heart Circ Physiol 293: H238H245.[Crossref] [Google Scholar]
  34. Peraza-Cruces K, Gutierrez-Guedez L, Castaneda Perozo D, Lankford CR, Rodriguez-Bonfante C, Bonfante-Cabarcas R, , 2008. Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro. Braz J Med Biol Res 41: 796803.[Crossref] [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.15-0255
Loading
/content/journals/10.4269/ajtmh.15-0255
Loading

Data & Media loading...

  • Received : 31 Mar 2015
  • Accepted : 28 Jan 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error