Abstract
Chagas’ disease, caused by Trypanosoma cruzi, leads to acute myocarditis and chronic cardiomyopathy. Myocardial structure and function were evaluated in T. cruzi (Brazil strain)-infected CD1 mice by histopathology, cardiac gated magnetic resonance imaging (MRI) and transthoracic echocardiography. There was a significant reduction in inflammation and fibrosis in infected mice treated early in infection. In mice treated late in infection, echocardiography revealed a significant increase in the end diastolic diameter and a decrease in percent fractional shortening and relative wall thickness. MRI revealed an increase in the right ventricular internal dimension. These findings, consistent with a dilated cardiomyopathy, were ameliorated in the early but not in the late treatment group, demonstrating that late treatment with verapamil is ineffective in reversing the development of chagasic cardiomyopathy in chronically infected mice. Our data underscore the hypothesis that early events determine the progression to cardiomyopathy and that early treatment with verapamil can prevent such progression.
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Berrebi A, Shtalrid M, Klepfish A, Bassous L, Kushnir M, Shulman L, Vorst E, Hahn T (1994). Verapamil inhibits B-cell proliferation and tumor necrosis factor release and induces a clinical response in B-cell chronic lymphocytic leukemia. Leukemia 8:2214–2216
Bonadonna G, Lechi C, Corradini P, Sinigaglia D, De Togni P, Miroslawa G (1986) Verapamil inhibits platelet aggregation by a calcium-independent mechanism. Thromb Haemost 56:308–310
Chandra M, Shirani J, Shtutin V, Weiss LM, Factor SM, Petkova SB, Rojkind M, Dominguez Rosales JA, Jelicks LA, Morris SA, Wittner M, Tanowitz HB (2002) Cardioprotective effects of verapamil on myocardial structure and function in a murine model of chronic Trypanosoma cruzi infection (Brazil Strain): an echocardiographic study. Int J Parasitol 32:207–215
Cohn RD, Durbeej M, Moore SA, Coral-Vazquez R, Prouty S, Campbell KP (2001) Prevention of cardiomyopathy in mouse model lacking the smooth muscle sarcoglycan-sarcospan complex. J Clin Invest 107: R1–R7
Dong R, Liu P, Wee L, Butany J, Sole MJ (1992) Verapamil ameliorates the clinical and pathological course of murine myocarditis. J Clin Invest 90:2022–2030
Factor SM, Minase T, Cho S, Dominitz R, Sonnenblick EH (1982) Microvascular spasm in the cardiomyopathic Syrian hamster: a preventable cause of myocardial necrosis. Circulation 66:342–354
Haug C, Voisard R, Baur R, Hannekum A, Hombach V, Gruenert A (1998) Effect of diltiazem and verapamil on endothelin release by cultured human coronary smooth-muscle cells and endothelial cells. J Cardiovasc Pharmacol [Suppl 1] 31:S388-S391
Huang H, Calderon TM, Berman JW, Braunstein VL, Weiss LM, Wittner M, Tanowitz HB (1999a) Infection of endothelial cells with Trypansoma cruzi activates NF-κB and induces vascular adhesion molecule expression. Infect Immun 67:5434–5440
Huang H, Chan J, Wittner M, Jelicks LA, Morris SA, Factor SM, Weiss LM, Braunstein VL, Bacchi CJ, Yarlett N, Chandra M, Shirani J, Tanowitz HB (1999b) Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice. J Mol Cell Cardiol 31:75–88
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 61:207–214
Kawai C (1999) From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation 99:1091–1100
Kirchhoff LV, Weiss LM, Wittner M, Tanowitz HB (2004) Parasitic diseases of the heart. Front Biosci 9:706–723
Leon JS, Engman DM (2003) The significance of autoimmunity in the pathogenesis of Chagas heart disease Front Biosci 8:e315–322
Martinez LL, Apparecida De Oliveira M, Fortes ZB (1999) Influence of verapamil and diclofenac on leukocyte migration in rats. Hypertension 34:997–1001
Morris SA, Weiss LM, Factor S, Bilezikian JP, Tanowitz H, Wittner M (1989) Verapamil ameliorates clinical, pathologic and biochemical manifestations of experimental chagasic cardiomyopathy in mice. J Am Coll Cardiol 14:782–789
Petkova SB, Huang H, Factor SM, Pestell RG, Bouzahzha B, Jelicks LA, Weiss LM, Douglas SA, Wittner M, Tanowitz HB (2001) The role of endothelin in the pathogenesis of Chagas’ disease. Int J Parasitol 31:499–511
Rassi AJr, Rassi A, Little WC (2000) Chagas’ heart disease. Clin Cardiol 23:883–889
Romana CA, Brunstein D, Collin-Delavaud A, Sousa O, Ortega-Barria E (2003) Public policies of development in Latin America and Chagas’ disease. Lancet 362:579
Rossi MA, Ramos SG, Bestetti RB (2003) Chagas’ heart disease: clinical-pathological correlation. Front Biosci 8:e94–109
Sakaguchi S, Iizuka Y, Furusawa S, Takayanagi M, Satoh S (2002) Preventive effects of a verapamil against tumor necrosis factor-alpha-induced shock symptoms: approached from lipoprotein metabolic disorders. Int Immunopharmacol 2:867–873
Salomone OA, Caeiro TF, Madoery RJ, Amuchastegui M, Omelinauk M, Juri D, Kaski JC (2001) High plasma immunoreactive endothelin levels in patients with Chagas’ cardiomyopathy.Am J Cardiol 87:1217–1220
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn DJ, Schnittger I (1989). Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of two-dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367
Sonnenblick EH, Fein F, Capasso JM, Factor SM (1985) Microvascular spasm as a cause of cardiomyopathies and the calcium-blocking agent verapamil as potential primary therapy. Am J Cardiol 55:179B–184B
Tanowitz HB, Morris SA, Weiss LM, Bilezikian JP, Factor SM, Wittner M (1989) Effect of verapamil on the development of chronic experimental Chagas’ disease. Am J Trop Med Hyg 41:643–649
Tanowitz HB, Kirchhoff LV, Simon D, Morris SA, Weiss LM, Wittner M (1992) Chagas’ disease. Clin Microbiol Rev 4:400–419
Tanowitz HB, Wittner M, Chen B, Huang H, Weiss LM, Christ GJ, Braunstein V, Bilezikian JP, Morris SA (1996a) Effects of verapamil on acute murine Chagas’ disease. J Parasitol 82:814–819
Tanowitz HB, Kaul DK, Chen B, Morris SA, Factor SM, Weiss LM, Wittner M (1996b) Compromised microcirculation in acute Trypanosoma cruzi infection. J Parasitol 82:124–130
Tanowitz HB, Wittner M, Morris SA, Zhao W, Weiss LM, Hatcher VB, Braunstein VL, Huang H, Douglas SA, Valcic M, Spektor M, Christ GJ (1999) The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi. Endothelium 6:217–230
Tarleton RL (2001) Parasite persistence in the aetiology of Chagas’ disease. Int J Parasitol. 31:550–554
World Health Organisation (1997) Chagas’ disease. Tropical Disease Research, Thirteenth Program Report. UNDP/WB/TDR, Geneva
Yamaguchi M, Suwa H, Miyasaka M, Kumada K (1997) Selective inhibition of vascular cell adhesion molecule-1 expression by verapamil in human vascular endothelial cells. Transplantation 63:759–764
Acknowledgements
These studies were supported by NIH grants AI-12770 and HL-07372 (HBT) and the Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES). All experiments described comply with the laws of the United States of America. We wish to thank Dazhi Zhao for excellent technical support.
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De Souza, A.P., Tanowitz, H.B., Chandra, M. et al. Effects of early and late verapamil administration on the development of cardiomyopathy in experimental chronic Trypanosoma cruzi (Brazil strain) infection. Parasitol Res 92, 496–501 (2004). https://doi.org/10.1007/s00436-004-1080-1
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DOI: https://doi.org/10.1007/s00436-004-1080-1