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Abnormalities of the coronary microcirculation in acute murine Chagas' disease
Insights
Abnormalities in the cardiac microcirculation of mice infected with Trypanosoma cruzi were observed early in infection. These vascular lesions, including constriction and dilation, may contribute to the development of Chagasic heart disease.
Area of Science:
- Cardiovascular Pathology
- Infectious Diseases
- Microcirculation Research
Background:
- Chronic Chagasic heart disease shares features with other cardiomyopathies, such as chamber enlargement and scarring.
- While immunologic factors are implicated, focal cardiac damage may stem from coronary microcirculation abnormalities.
- Previous studies indicated microvascular hyperreactivity in other cardiomyopathy models.
Purpose of the Study:
- To investigate abnormalities in the cardiac microcirculation during acute Trypanosoma cruzi infection in mice.
- To determine if early vascular changes correlate with the pathogenesis of Chagasic heart disease.
Main Methods:
- Mice were infected with Trypanosoma cruzi and perfused with silicone rubber at 15-17 days post-infection.
- Cardiac microvasculature (arterioles, capillaries, venules) was analyzed after tissue clearing.
- Lesions were compared between infected and control animals.
Main Results:
- Infected mice exhibited focal vascular constriction, microaneurysm formation, dilatation, and microvessel proliferation.
- These vascular lesions were absent in control animals.
- The observed vascular pathology occurred with minimal cardiac degeneration or fibrosis.
Conclusions:
- Early-stage Trypanosoma cruzi infection induces significant abnormalities in the cardiac microcirculation.
- These vascular lesions may play a crucial role in the early pathogenesis of myocardial damage in Chagas' disease.
- Findings support the hypothesis of abnormal myocardial microcirculation in Chagas' disease.
Abstract:
Chronic Chagasic heart disease has many features characteristic of other congestive cardiomyopathies, including ventricular and atrial chamber enlargement, hypertrophy, focal scarring, and mural thrombi. Histologically, there is often lymphocytic inflammation, spotty necrosis, and few parasites. Although immunologic mechanisms have been invoked to explain the development of myocardial degeneration, there have been suggestions that the focal alterations in the heart are secondary to abnormalities of the coronary microcirculation. Based on work from our laboratories which has demonstrated microvascular hyperreactivity in several other models of congestive cardiomyopathy, we investigated whether the cardiac microcirculation of mice acutely infected with Trypanosoma cruzi was also abnormal. We perfused animals at 15-17 days post-infection with silicone rubber which fills the arterioles, capillaries, and venules of the beating heart. After clearing the tissue, we observed numerous areas of focal vascular constriction, microaneurysm formation, dilatation, and proliferation of microvessels which were not present in control animals. These lesions were similar to those we have observed in other congestive cardiomyopathies. Since at this stage of infection there is minimal cardiac degeneration or fibrosis, the presence of these vascular lesions even early in Chagas' disease, may be significant for the pathogenesis of focal myocardial damage. These observations during acute infection provide additional support for the suggestions of others that the myocardial microcirculation is abnormal in Chagas' disease.