Studies of membrane fluidity and heart contractile force in Trypanosoma cruzi infected mice

In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of beta-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac beta-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 ± 0.36) in both the acute (78.24 ± 1.67) and indeterminate phases (77.28 ± 0.91), but lower in the chronic disease (53.32 ± 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65 percent of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to beta-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac beta-adrenergic receptors suggests a correlation between the modified beta-adrenergic receptors affinity and the cardiac contractile force.

Influence of Antedorsal Thalamic nuclei on the hypophyseal-adrenal axis and cardiac beta receptors in tars submitted to vatriable chronic stress

The limbic structures play an important role in the control of the neuroendocrine and sympathical adrenal function in basal and stress conditions. This work was undertaken to evaluate plasma ACTH, adrenocortical activity, cardiac adrenoceptors density and affnity response to variable chronic stress (VCS) in anterodorsal thalamic nuclei (ADTN) lesioned rats. Thirty days after lesion, shamlesioned stressed animals increased plasma ACTH and corticosterone as compared to sham-lesioned unstressed animals (p<0.05); lesioned rats increased ACTH levels after VCS (p<0.05) as compared unstressed-lesioned rats. Whereas in sham-lesion plasma corticosterone (C) increased after stress. in lesioned animals (C) remained unchanged as compared to unstressed-lesioned animals. In the stressed groups, adrenal C contents were below those found in unstressed rats. Beta-receptors affinity, in all the experimental groups, was similar, but VCS sham-lesioned animals underwent a significant increase in cardiac D-adrenergic receptors density when compared with basal and lesioned groups (P<0.001). Our findings would demonstrate that the increment in cardiac Beta adrenoceptors density appears as a consequence of the increase in ACTH, plasma corticosterone and sympathetic response provoked by stress situations. ADTN lesion attenuated this hipophisoadrenal system response to chronic stress as well as the above mentioned cardiac beta adrenoceptors density increment.

Experimental Chagas' disease: effects of propranolol upon cardiac beta-receptors

Chagas' disease is an important cause of heart disfunction in Latin America. Previous works from our laboratory reproducing experimental Chagas' disease in mice, demonstrated that the affinity and density of cardiac beta-adrenergic receptors were altered during the acute, indeterminate and chronic phase in Albino Swiss mice inoculated with Trypanosoma cruzi. Keeping in mind that Propranolol is a beta-blocking agent that binds in the same receptors'site, which we have described as altered along T. cruzi infection. The present study was performed to determine if a beta-blocker treatment could prevent cardiac beta-receptors'disorders provoked by T. cruzi infection. Two different doses of Propranolol (9 and 40 mg/Kg/day) were injected in the mice during 3 days; then they were infected with 7 x 10(4) parasites/mouse and propranolol was continued daily for one week. The results showed that the concentrations of propranolol used did not protect the beta-receptors'sites by administration of each doses.

Cardiac beta receptors' density or affinity modified by different Trypanosoma cruzi amount

Chagas'disease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and anatogonist studied at 30 days post-infection (p.i.). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with (3)H/DHA. The AcH group presented less cardiac beta receptors number (p<0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p<0.01) but desinty, was not different from non infected animals. Beta receptors'affinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy.

Cardiac B-receptors in experimental Chagas`disease

Estudaram-se os receptores beta cardiacos de camundongos infectados pelo Trypanosoma cruzi na fase pos-aguda da doenca de Chagas para estabelecer em que medida os mesmos contribuem a gerar respostas anomalas as catecolaminas observadas nestes miocardios. Utilizara-se 3-H/DHA para a marcacao dos receptores beta cardiacos dos camundongos normais e dos infectados na fase pos-aguda (45 a 90 dias pos-infeccao). O numero dos sitios de fixacao foi similar nos dois grupos, 78.591 ñ 3.125 fmol/mg. Proteina no grupo controle. Em vez disso, a afinidade verificou-se significamente diminuida no grupo chagasico (Kd = 7.299 ñ 0.212 nM) p < 0.001. Os resultados obtidos demonstraram que as modificacoes observadas na estimulacao adrenergica do miocardio chagasico se correlacionam com a menor afinidade dos receptores beta cardiacos e que estas alteracoes exerceriam uma parte determinante para as consequencias funcionais que sao detectadas na fase cronica.