[Role of mitochondria and reactive oxygen species in the progression of heart failure]. / Rol de las mitocondrias y de las especie reactivas de oxigeno en la pro-gresion de la insuficiencia cardiaca.

Congestive heart failure (CHF) would be associated with mitochondrial abnormalities and increased of reactive species of oxygen (ROS). To clarify these issues we studied the structure, function of the mitochondrial enzyme nitro oxide synthase inducible (iNOS) and lipoperoxidation of membranes, one of their products through the peroxide nitrite ion (ONOO-), in the heart muscle of patients with heart failure congestive (ICC) grade III and IV (according to New York Heart Association). We included 25 patients who underwent cardiovascular surgery to biopsies of the heart muscle. They were stratified into a group with CHF (n = 18) and control group (n = 7). In di-chas biopsies analyzed the enzymatic activity of mitochondrial complex III spectrophotometrically, which was measured in mM.ubiquinona-1.mg prot, while the mitochondrial morphology was analyzed by the Zeiss electron microscope, the areas were quantified with program Axionvision 4.6. Lipoperoxidation of membranes was measured by the presence of ONOO-by immunohistochemistry against primary antibody against 3-nitrotyrosine was used lab kit system biogenic steptobidin biotin peroxidase (SBA) and coloring triamiobencidina (TAB), it is made with semicuantificacion intensity SCORE test. The statistical test used was ANOVA. The heart muscle of patients with CHF showed that the mitochondrial area was reduced by 78% compared with the control (160.37 µm2 ± 9.87) (936.81 µm2 ± 78.48) p 0.0001. There was also a 70% reduction in complex III activity compared to control (1.9 10-2 mM ubiq.mim-prot 1.mg ± 12.6) (5.79 10-2mM ubiq.mim prot-1.mg ± 36.6) p . The presence of ONOO-was significantly increased in patients with CHF. Alterations ultraestructutural and functional mitochondria found in patients with CHF and increased ROS are involved in the measures of physiopathology CCI and whites should be taken into account for future therapies of this condition.

Changes in the cardiac beta-adrenergic system provoked by different T. cruzi strains.

BACKGROUND: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology. METHODS: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus. RESULTS: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain. CONCLUSIONS: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.

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.

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 receptorssite, 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-receptorsdisorders 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-receptorssites by administration of each doses. (AU)

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 beta receptors density or affinity modified by different Trypanosoma cruzi amount

Chagasdisease 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 receptorsaffinity 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. (AU)