Exercise Performance and Skeletal Muscles in Patients With Advanced Chagas Disease

de, María Montes; Torres, Sonia H.; Loyo, José G.; Vazquez, Francia; Hernández, Noelina; Anchustegui, B; Puigbó, Juan José

doi:10.1378/chest.125.4.1306

Cited by 35 publications

(28 citation statements)

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“…Previously, we have demonstrated that, in the mouse model of Chagas' disease, there is a significant reduction in blood flow in the cremaster bed as well as in the coronary circulation (37,38). In primates and humans, there is evidence for vascular dysfunction; however, the presence and amount of vascular dysfunction varies with the stage of the disease (4,22,42,43,45).…”

Section: The Levels Of P21mentioning

confidence: 99%

Trypanosoma cruzi Infection Induces Proliferation of Vascular Smooth Muscle Cells

Hassan

Mukherjee²,

Nagajyothi³

et al. 2006

Infect Immun

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Trypanosoma cruzi infection causes cardiomyopathy and vasculopathy. Previous studies have demonstrated that infection of human umbilical vein endothelial and smooth muscle cells resulted in activation of extracellular signal-regulated kinase (ERK).In the present study, smooth muscle cells were infected with trypomastigotes, and immunoblot analysis revealed an increase in the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), important mediators of smooth muscle cell proliferation. Interestingly, after infection, the expression of caveolin-1 was reduced in both human umbilical vein endothelial cells and smooth muscle cells. Immunoblot and immunohistochemical analyses of lysates of carotid arteries obtained from infected mice revealed increased expression of PCNA, cyclin D1, its substrate, phospho-Rb (Ser780), and phospho-ERK1/2. The expression of the cyclin-dependent kinase inhibitor p21Cip1/Waf1 , caveolin-1, and caveolin-3 was reduced in carotid arteries obtained from infected mice. There was an increase in the abundance of pre-pro-endothelin-1 mRNA in the carotid artery and aorta from infected mice. The ET A receptor was also elevated in infected arteries. ERK activates endothelin-1, which in turn exerts positive feedback activating ERK, and cyclin D1 is a downstream target of both endothelin-1 and ERK. There was significant incorporation of bromodeoxyuridine into smooth muscle cell DNA when treatment was with conditioned medium obtained from infected endothelial cells. Taken together, these data suggest that T. cruzi infection stimulates smooth muscle cell proliferation and is likely a result of the upregulation of the ERK-cyclin D1-endothelin-1 pathway.Chagas' disease, caused by Trypanosoma cruzi, results in acute myocarditis and chronic cardiomyopathy (38, 39) accompanied by a vasculopathy (23,30,31,34,37,43). The precise etiology of chagasic heart disease is multifactorial, involving parasite persistence (41), inflammation (13, 35), autoimmunity (20), and vascular dysfunction (37). The evidence for vascular dysfunction in Chagas' disease includes infection-associated microvascular spasm, reduction in blood flow, increased platelet aggregation in experimental infection, and increased myocardial inflammation and fibrosis (24,34,40).T. cruzi infects many cell types that comprise the cardiovascular system, including cardiac myocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. The interaction of the parasite with endothelial cells is among the first encounters in the host-parasite relationship. Studies from our laboratory and others have demonstrated that infection of endothelial cells with T. cruzi results in the expression of proinflammatory cytokines (35), vascular adhesion molecules (13), and the vasoactive peptide endothelin-1 (ET-1) (27)(28)(29).The cells of the cardiovascular system synthesize ET-1 and have endothelin receptors. ET-1 acts locally on cells such as cardiac myocytes, cardiac fibroblasts, endothelial cells, and smooth muscle cells via two t...

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Section: The Levels Of P21mentioning

confidence: 99%

Trypanosoma cruzi Infection Induces Proliferation of Vascular Smooth Muscle Cells

Hassan

Mukherjee²,

Nagajyothi³

et al. 2006

Infect Immun

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“…However, it is well recognized that the determination of exercise tolerance is multifactorial. Thus, as T. cruzi is able to parasitize and damage structures such as peripheral nerves and skeletal muscles, equally important elements in determining the exercise tolerance (Meiler et al 1987;Montes de Oca et al 2004), we cannot attribute the results exclusively to cardiac and cellular changes. In this context, the weak correlation between single cardiomyocyte contractile parameters and workload indicates that other organs and tissues should be investigated to improve the knowledge about the pathophysiological mechanism related to exercise intolerance in Chagas' disease.…”

Section: Discussionmentioning

confidence: 98%

“…Thus, as T. cruzi is able to parasitize and damage structures such as peripheral nerves and skeletal muscles, equally important elements in determining the exercise tolerance (Meiler et al. 1987; Montes de Oca et al. 2004), we cannot attribute the results exclusively to cardiac and cellular changes.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it is not known whether T. cruzi infection can also lead to changes in exercise tolerance in experimental animal models. The reduction of exercise tolerance in individuals with Chagas' disease is multifactorial and is involved with pathological changes in several organs and tissues, such as peripheral nervous system, skeletal and cardiac muscles (Meiler et al 1987;Montes de Oca et al 2004). Moreover, previous studies indicated that atrial and ventricular mechanical and electrical abnormalities may have an important role in exercise intolerance in Chagas' disease (Gallo et al 1975;Mady et al 2000;Lima et al 2010).…”

Section: University Of Viçosa Viçosa Minas Gerais Brazilmentioning

confidence: 99%

“…The reduction of exercise tolerance in individuals with Chagas’ disease is multifactorial and is involved with pathological changes in several organs and tissues, such as peripheral nervous system, skeletal and cardiac muscles (Meiler et al. 1987; Montes de Oca et al. 2004).…”

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Effects of Trypanosoma cruzi infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats

Novaes

Penitente

Gonçalves

et al. 2011

Int J Experimental Path

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The aim of this study was to investigate the effects of Trypanosoma cruzi (T. cruzi) infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats. Adult Wistar rats were randomized into control (n = 14) and infected (n = 14) groups. Infected animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes/50 g body weight). After 9 weeks, the animals were subjected to a treadmill running protocol. Then, the right atrium (RA) and left ventricle (LV) were removed for morphological and cell contractile evaluation. The infected animals exhibited a significant reduction in distance travelled, total time to fatigue and workload. In addition, these animals had hypertrophy, increased myocardial cellularity, and an increase in the proportion of collagen and blood vessels. RA and LV myocytes from infected animals showed marked contractile dysfunction under basal conditions and a reduced contractile response to β-adrenergic stimulation. The workload of infected animals was correlated closely with the amplitude of cell shortening of RA and LV myocytes. T. cruzi infection influenced the myocardial morphology and the mechanical properties of RA and LV single myocytes negatively and reduced exercise tolerance. Single cardiomyocyte contractile dysfunction could constitute an additional mechanism of cardiac impairment and reduced exercise tolerance in this infection.

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Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

et al. 2020

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Aims Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone-Heart Failure trial (TESTO-HF; Brazil) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF; Germany)]. Methods and results A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO-HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA-HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X-ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m 2 (ALM/height 2) and handgrip strength cutoff for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO 2) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO 2 as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043-2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011-1.374; P = 0.035) were independent predictors for peak VO 2 adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF. Conclusions Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.

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Exercise Performance and Skeletal Muscles in Patients With Advanced Chagas Disease

Cited by 35 publications

References 32 publications

Trypanosoma cruzi Infection Induces Proliferation of Vascular Smooth Muscle Cells

Trypanosoma cruzi Infection Induces Proliferation of Vascular Smooth Muscle Cells

Effects of Trypanosoma cruzi infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies

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