Apoptosis in a canine model of acute Chagasic myocarditis

Histologic, ultrastructural and nick end labeling studies were made to eval ute the occurrence of apoptosis in the hearts of dogs with acute myocarditi s due to experimental infection with T. cruzi. The best results for the det ection of apoptosis by nick end labeling were obtained by a method combinin g the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-c onjugated deoxyuridine triphosphate. followed by counterstaining of DNA wit h 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning con focal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes : (2) endothelial cells of capillaries and venules: (3) immune effector cel ls, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracel lular forms of T, cruzi. The apoptosis in myocytes and endothelial cells af fected cells that were not infected by T, cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune eff ector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apopt osis in T, cruzi confirms the results of other studies showing that this ph enomenon occurs during the differentiation of trypomastigotes in vitro. Thu s. apoptosis constitutes an important and multifactorial event in the patho genesis of acute Chagasic myocarditis. (C) 1999 Academic Press.