Cardiac beta-receptors in experimental Chagas' disease

Enders, Jürgen; Paglini, P; Fernández, Alicia Ruth; Marco, Fernanda; Palma, J. A.

doi:10.1590/s0036-46651995000100009

Cited by 9 publications

(4 citation statements)

References 6 publications

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“…Previous studies from our laboratory have demonstrated that the chronic indeterminate phase is not so 'silent' as has been described: modifications of cardiac contractility, alterations of some components of the cardiac β adrenergic system (Enders et al 1995;, and electrocardiographic alterations (Bustamante et al 2003) were previously found. Now we have demonstrated that the responsible organelle for cardiac energy supply is also compromised both structurally and functionally.…”

Section: Measurementsmentioning

confidence: 64%

Chronic indeterminate phase of Chagas’ disease: mitochondrial involvement in infection with two strains

et al. 2012

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Chagasic cardiopathy has become one of the most frequent causes of heart failure and sudden death, as well as one of the most common causes of cardio-embolic stroke in Latin America. The myocyte response to oxidative stress involves the progression of cellular changes, primarily targeting the mitochondria and modifying therefore the energy supply. In this paper we analysed the effect of the infection of mice with 2 different strains of Trypanosoma cruzi (Tulahuen and SGO Z12) in the chronic indeterminate stage (75 days post-infection), upon the structure and function of cardiac mitochondria. The structural results showed that 83% of the mitochondria from the Tulahuen-infected mice presented an increase in their matrix and 91% of the mitochondria from the SGO Z12-infected group showed a reduction in their diameter (P < 0.05). When the Krebs cycle and mitochondrial respiratory chain functionality was analysed through the measurement of the citrate synthase and complexes I to IV activity, it showed that their activity was altered in all cases in a similar manner in both infected groups. In this paper we have demonstrated that the chronic indeterminate phase is not 'silent' and that cardiac mitochondria are clearly involved in the genesis and progression to the chronic chagasic cardiopathy when different factors alter the host-parasite equilibrium.

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Section: Measurementsmentioning

confidence: 64%

Chronic indeterminate phase of Chagas’ disease: mitochondrial involvement in infection with two strains

et al. 2012

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“…However, in the present study, only parasitic load and histopathological and morphological analyses were performed, which we considered insufficient to confirm CIF. Furthermore, other studies using experimental CIF models have shown modifications of cardiac contractility, alterations of some components of the cardiac b adrenergic system, and ECG alterations (48,49,86). Theoretically, the CIF of CD is a stage of host-parasite equilibrium that may explain the apparent clinical silence (4).…”

Section: Discussionmentioning

confidence: 99%

Physical Exercise Promotes a Reduction in Cardiac Fibrosis in the Chronic Indeterminate Form of Experimental Chagas Disease

et al. 2021

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Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease and a health problem in Latin America. Etiological treatment has limited effectiveness in chronic CD; thus, new therapeutic strategies are required. The practice of physical exercises has been widely advocated to improve the quality of life of CD patients. The most frequent clinical CD manifestation is the chronic indeterminate form (CIF), and the effect of physical exercises on disease progression remains unknown. Here, in a CIF model, we aimed to evaluate the effect of physical exercises on cardiac histological, parasitological, mitochondrial, and oxidative metabolism, electro and echocardiographic profiles, and immunological features. To establish a CIF model, BALB/c and C57BL/6 mice were infected with 100 and 500 trypomastigotes of the Y T. cruzi strain. At 120 days postinfection (dpi), all mouse groups showed normal PR and corrected QT intervals and QRS complexes. Compared to BALB/c mice, C57BL/6 mice showed a lower parasitemia peak, mortality rate, and less intense myocarditis. Thus, C57BL/6 mice infected with 500 parasites were used for subsequent analyses. At 120 dpi, a decrease in cardiac mitochondrial oxygen consumption and an increase in reactive oxygen species (ROS) were detected. When we increased the number of analyzed mice, a reduced heart rate and slightly prolonged corrected QT intervals were detected, at 120 and 150 dpi, which were then normalized at 180 dpi, thus characterizing the CIF. Y-infected mice were subjected to an exercise program on a treadmill for 4 weeks (from 150 to 180 dpi), five times per week in a 30–60-min daily training session. At 180 dpi, no alterations were detected in cardiac mitochondrial and oxidative metabolism, which were not affected by physical exercises, although ROS production increased. At 120 and 180 dpi, comparing infected and non-infected mice, no differences were observed in the levels of plasma cytokines, indicating that a crucial biomarker of the systemic inflammatory profile was absent and not affected by exercise. Compared with sedentary mice, trained Y-infected mice showed similar parasite loads and inflammatory cells but reduced cardiac fibrosis. Therefore, our data show that physical exercises promote beneficial changes that may prevent CD progression.

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“…Cardiac β receptors affinity and density are modified in different manner in each T. cruzi infection stage (Enders et al 1995) indicating different degrees in cardiac function alteration. For this reason clomipramine efficiency was also evaluated studying β receptors behavior.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment

et al. 2008

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Treatment of Chagas disease is a controversial issue because the available drugs are highly toxic. Clomipramine is a tricyclic antidepressant drug that inhibits Trypanosoma cruzi's trypanothione reductase, provoking the death of the parasite and preventing the cardiac damage when used for the treatment of acutely infected mice. Here, we studied the effectiveness of clomipramine (5 mg/kg/day for one month) as chemotherapy for T. cruzi-infected mice in the chronic indeterminate stage of the infection. The animals were analyzed in the cardiac chronic phase. Survival of treated animals was 84% while for the untreated ones was 40%; most of the animals presented electrocardiographic abnormalities. Affinity and density of cardiac beta receptors from infected and treated mice were similar to those in the indeterminate phase, showing that clomipramine treatment stopped the increment of functional alterations provoked by the infection, while untreated mice presented affinity and density significantly diminished. Hearts from infected and untreated mice in the chronic stage presented mononuclear cells, necrosis and fiber dissolution while hearts from treated animals showed only isolated inflammatory infiltrates. Present results demonstrate that clomipramine used in the chronic indeterminate phase of the T. cruzi infection modified the natural evolution of the chagasic cardiopathy.

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Cardiac beta-receptors in experimental Chagas' disease

Cited by 9 publications

References 6 publications

Chronic indeterminate phase of Chagas’ disease: mitochondrial involvement in infection with two strains

Chronic indeterminate phase of Chagas’ disease: mitochondrial involvement in infection with two strains

Physical Exercise Promotes a Reduction in Cardiac Fibrosis in the Chronic Indeterminate Form of Experimental Chagas Disease

Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment

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