Microcirculation and Chagas' Disease: Hypothesis and Recent Results

Ramos, Simone G.; Rossi, Marcos A.

doi:10.1590/s0036-46651999000200011

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…Transient microvascular ischemic disturbances of low intensity and short duration have been postulated to be the causative mechanisms of Chagas cardiomyopathy. This could explain the focal distribution of cell necrosis and subsequent reparative interstitial fibrosis found in Chagasic hearts, which was similar to what is seen in experimental models of ischemia and reperfusion (Ramos and Rossi, 1999). In addition, coalescent microinfarctions have been postulated to occur in watershed coronary areas, because of unopposed sympathetic overstimulation.…”

Section: Microvascular Abnormalities and Ischemiasupporting

confidence: 65%

“…In mice infected with T. cruzi, microcirculatory abnormalities include focal vascular constriction, microvascular proliferation, and occlusive platelet thrombi in small epicardial and intramural coronary arteries, which lead to ischemia (Factor et al, 1985;Marin-Neto et al, 2007;MarinNeto and Rassi, 2009;Ramos and Rossi, 1999;Rossi and Ramos, 1996). The impairment of cardiac sympathetic function at the ventricular level that occurs early in the course of Chagas cardiomyopathy is related to regional myocardial perfusion disturbances (Hiss et al, 2009).…”

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

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Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Section: Microvascular Abnormalities and Ischemiasupporting

confidence: 65%

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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“…Increased expression of TGF-b1 mRNA and protein in myocardium bordering the infarct region have been associated with cardiac wound-healing response [24]. Because, in patients with Chagas disease, there is microthrombus formation, micromyocardial infarction, and inflammatory reaction [22,25], the enhancement of TGF-b1/Smad signaling might reflect a secondary reaction to the remodeling of the infarct scars after completion of wound healing per se. However, it is also possible that the enhanced TGF-b1 pathway activation that we observed could be directly involved in the intense synthesis and secretion of ECM molecules (including fibronectin) occurring in the fibrotic process.…”

Section: Discussionmentioning

confidence: 99%

Implication of Transforming Growth Factor–β1 in Chagas Disease Myocardiopathy

Araújo-Jorge¹,

Waghabi²,

Hasslocher‐Moreno

et al. 2002

J INFECT DIS

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Cardiac dysfunction with progressive fibrosis is a hallmark of Chagas disease. To evaluate the involvement of transforming growth factor (TGF)-beta1 in this disease, TGF-beta1 levels in patients were measured at 3 stages: asymptomatic indeterminate (IND), cardiac with no or slight heart dysfunction (Card 1), and cardiac with moderate or severe heart dysfunction (Card 2). All patients had significantly higher circulating levels of TGF-beta1 than did healthy persons, and 27% of patients in the Card 1 group had higher TGF-beta1 levels than did patients in the IND group. Immunohistochemical analysis of cardiac biopsy specimens showed strong fibronectin staining in the extracellular matrix and staining for phosphorylated Smad 2 (activation of the TGF-beta1 signaling pathway) in cell nuclei. The higher levels of latent TGF-beta1 observed in patients with myocardiopathy, together with intracellular activation of the TGF-beta1 pathway and tissue fibrosis, suggest that TGF-beta1 plays an important role in Chagas disease. TGF-beta1 may represent a new target for preventive and curative treatments of Chagas disease.

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“…Another hypothesis suggests that cardiac parasympathetic denervation leads to chronic Chagas' disease 14,15 . Yet, another hypothesis relates chagasic heart disease to alterations in the microcirculation 16 . The clinical manifestations of the chronic phase include anginal thoracic pain, symptomatic disorder of the conduction system and sudden death, and progressive chronic heart failure with predominance on the right side in advanced cases.…”

Section: Discussionmentioning

confidence: 99%

A sixty-four-year-old woman with Chagas' disease, who underwent implantation of a permanent cardiac pacemaker and evolved with rapidly progressive heart failure

Medeiros¹,

Benvenuti²,

Costa³

2001

Arq. Bras. Cardiol.

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A 64-year-old female patient sought medical assistance at our hospital due to dyspnea on light exertion and even at rest.The patient had been experiencing dyspnea on strenuous exertion since the age of 52 years, which progressed in 10 years to dyspnea on light exertion and even orthopnea.On physical examination (9/1/97), her pulse was regular, her heart rate was 56bpm, and her blood pressure was 140/170mmHg. Her lung examination was within the normal range. The cardiac ictus could be felt on the left 6 th intercostal space over the length of 2 fingertips. A systolic thrill was palpated on the 6 th intercostal space. The cardiac sounds were normal. A systolic cardiac murmur (++/4) was heard on the mitral area and a diastolic cardiac murmur was heard on the aortic area. The abdominal examination was within the normal range and no edema of the lower limbs was observed.The chest X-ray showed enlargement of the cardiac silhouette (++++/4) and normal pulmonary fields.Electrocardiography (8/27/97) showed an ectopic atrial rhythm, a P-R interval of 0.12 s, an initial disturbance of ventricular depolarization (initial QRS blurring in II, III, aVF, and V2), disorder of heart conduction of the anterosuperior left bundle-branch and the right branch, and alterations in ventricular repolarization ( fig. 1).The laboratory tests (8/27/97) were as follows: hemoglobin, 13.6g/dL; hematocrit, 39%; serum creatinine, 0.7mg/ dL; serum sodium, 141mEq/L; and serum potassium, 4.5mEq/L. The serum tests for Chagas' disease were positive.The diagnosis of heart failure due to Chagas' cardiomyopathy was established and the patient was prescribed 37.5mg of captopril and 25mg of hydrochlorothiazide daily.Echocardiography (12/18/97) showed diffuse hypokinesia of the left ventricle, ectasia of the aortic root, moderate regurgitation of the aortic and mitral valves, and pulmonary hypertension. The measurements are shown in table I.Chest tomography (3/31/99) revealed ectasia of the aortic root (52.66mm) and the following preserved diameters: ascending aorta (39.79mm), aortic arch (31.12mm and 25.76mm), descending aorta (26.27mm), and thoracoabdominal transition (21.4mm).The symptoms subsided, as did the dyspnea on moderate exertion. After 10 months, however, the dyspnea became more severe, being triggered on minimum exertion, and even orthopnea occurred (Sept '98). The patient then sought medical care, and an irregular cardiac rhythm was observed.Electrocardiography (9/3/98) showed an irregular rhythm of the atrial pacemaker with junctional escapes and ventricular premature depolarizations, QRS duration of 0.12 s, anterosuperior left bundle-branch block and block of the right branch ( fig. 2).Two months later, the patient required hospitalization (from 11/17/98 to 12/10/98) for control of heart failure.On physical examination (11/17/98), the patient had an irregular pulse, heart rate of 56 bpm, blood pressure of 110/ 80mmHg, crepitant rales in the base of her thorax, irregular cardiac rhythm due to frequent premature depolarizations, and a systolic...

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Microcirculation and Chagas' Disease: Hypothesis and Recent Results

Cited by 11 publications

References 37 publications

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

Implication of Transforming Growth Factor–β1 in Chagas Disease Myocardiopathy

A sixty-four-year-old woman with Chagas' disease, who underwent implantation of a permanent cardiac pacemaker and evolved with rapidly progressive heart failure

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