Cardiac myocyte nuclear size and ploidy status decrease after mechanical support.

Two patients with end-stage dilated cardiomyopathy of ischemic and idiopathic origin were treated with a left ventricular assist device (LVAD) as a bridge for heart transplantation. Myocardial tissue was collected during LVAD insertion and from the left ventricular apex of the explanted hearts. The myocyte diameter, nuclear area and DNA content of myocyte nuclei were measured by static cytomorphometry in tissue sections and in isolated myocytes with a digital analysis system. The presence of apoptotic nuclei was investigated by the TdT mediated X-dUTP nick end labeling technique (TUNEL). The prolonged use of a LVAD was associated with a reduction in myocyte diameter, indicating that the LVAD may induce a reversion of myocyte hypertrophy, a process described as "reverse remodeling." In addition, unloading of the heart induced a reduction in the size and DNA content of myocyte nuclei. These results suggest that the cardiomyocyte nuclei are in a dynamic state and, as it occurs with cell hypertrophy, nuclear hypertrophy and polyploidization may be a reversible phenomenon.

Trypanosoma cruzi: aberrant expression of class II major histocompatibility complex molecules in skeletal and heart muscle cells of chronically infected mice.

In isolated skeletal, heart, and smooth muscle cells from BALB/c and C3H/HeJ mice infected with different strains of Trypanosoma cruzi the presence of class II MHC molecules was investigated by immunocytochemical techniques. We employed single muscle fibers instead of conventional cryostat sections to obtain a more accurate antigen localization. Approximately half of the skeletal muscle cells isolated from the rectus femoris expressed Ia antigens on their surface, irrespective of the mouse or parasite strain combination. Ia expression was apparent only at 30 days postinfection and thereafter. The heart muscle cells expressed class II molecules only at 1 and 3 months postinfection. In no case did the smooth muscle cells from infected mice express Ia antigens. Studies of the same molecules in the noninfected animals gave constantly negative results. We conclude that in the course of the chronic infection of mice with T. cruzi, ectopic expression of class II MHC molecules occurs at the surface of skeletal and heart muscle cells, providing a possible mechanism for explaining the anti-striped muscle autoreactivity present in Chagas' disease.

Antiheart antibody-dependent cytotoxicity in the sera of mice chronically infected with Trypanosoma cruzi.

Sera of mice chronically infected with Trypanosoma cruzi contain antibodies that bind to the surface of living adult syngeneic heart muscle cells. In a syngeneic system, with nonadherent spleen mononuclear cells as effector cells and cardiocytes as targets, antibody-dependent cytotoxicity (ADCC), revealed by the liberation of creatine phosphokinase from damaged cardiocytes, was observed after incorporation of serum samples from infected mice. Target damage was decreased after absorption with syngeneic myocardium, but absorption with T. cruzi epimastigotes or trypomastigotes or with syngeneic skeletal muscle had no effect on ADCC. No complement-dependent lysis against heart muscle cells was detected in the same serum samples. These observations indicate that serum from chronically chagasic mice contain antibodies that bind to the surface of living adult syngeneic cardiocytes and are able to exert ADCC, suggesting that they could play a role in the pathogenesis of the heart damage that occurs in Chagas' disease.

Junin virus infection of guinea pigs: immunohistochemical and ultrastructural studies of hemopoietic tissue.

An association between viral antigens, cytopathic effect (CPE) and viral titers in blood and lymphoid tissues suggests a direct CPE of Junin virus on the lymphopoietic organs of guinea pigs infected with 10(3) 50% lethal doses of the XJ prototype strain. After seven days of infection, all lymphoreticular organs had infectivity titers higher than those for blood. Virus was recovered from bone marrow and lymph nodes at day 5 after infection; peak titers were obtained from bone marrow, spleen, and lymph nodes after day 10. Granular specific fluorescence was detected in the cytoplasm of reticular monocytes after day 7; megakaryocytes showed positive fluorescence, but specific staining of other lymphoid cells was not observed. Necrosis of bone marrow, lymph nodes, and spleen was observed after day 9. CPE consisted of overdevelopment of reticuloendoplasmic cisterne of reticulomonocytes and myeloblasts. Typical Junin virus particles were observed. Reticular cells were gradually destroyed, and simultaneous necrosis of surrounding lymphoid cells was observed.

Effect of chagasic sera on the rat isolated atrial preparation: immunological, morphological and function aspects.

An antibody reacting with the plasma membrane of working myocardial cells, skeletal muscle fibres, and endothelial cells (EVI antibody) has been described in the sera of patients with Chagas' disease. In the present study of rat isolated atrial preparations beating in ddifferent media, direct immunofluorescence and ultrastructural immunohistochemical procedures indicate that the antibody can interact with the living tissue, becoming fixed to the plasma membranes. Transmission electronmicroscopy studies also showed the presence of sarcolemmal alterations. These observations suggest a possible pathogenic effect of the EVI antibody. The presence of EVI-positive sera in the beating medium leads to a significant increase in the frequency of contractions; no significant effects of EVI-positive sera in contractile force were seen. The increase in frequency could be prevented by previous treatment with a b-adrenergic blocking agent (MJ-1999), but not by an x-blocker (phentolamine) or by an anti-histamine compound (cyproheptadine). The changes described were observed only in those atrial preparations which were beating in media containing EVI-positive sera. In those atria beating in control media (KR,KR plus normal human serum, KR plus EVI-negative chagasic serum), neither immunological nor morphological or functional changes wersence of EVI-positive chagasic serum diminished atrial stimulation after added norepinephrine. These results suggest the possibility that the EVI antibody may act as a b-adrenergic agonist at the cell plasma membrane level. Such an effect might account for some of the clinical features of chronic Chagas' heart disease.