An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

Figure 4

Myocardial, renal, and hepatic lesions induced by anthracyclines. (a–c) Representative photomicrographs of myocardial damage. (a) DOX2 group, grade 1: primary damage of the left ventricular myocardium. Highly intense eosinophilia of the cytoplasm, pyknotic nuclei [P], and diffuse vacuolar degenerations in cardiomyocytes [] are present. (b) DAU3 group, grade 4: conspicuous disperse toxic myocardial damage. Extensively vacuolated cardiomyocytes [] with intense eosinophilic cytoplasm are present. Necrotic cardiomyocytes [N] phagocytized by macrophages [M] were gradually replaced by proliferated connective tissue (e.g., thick wavy collagen fibers [arrows]). Mononuclear infiltrate [I] is present within the bundles of these fibers. (c) DAU3 group, grade 4: extensive fibrosis [arrows] in areas with myocytolysis and necrosis of cardiomyocytes. (d–f) Representative photomicrographs of renal damage. (d) DOX2 group, grade 1: initial renal tubular necrosis. Lesions of nephrosis with tubular degeneration [] are present. (e) DAU3 group, grade 4: focal severe nephropathy. Lesions of nephrosis with tubular degeneration and extensive necrosis [N] of tubular cells are frequent. Fibrosis [arrow] and mononuclear infiltrate [I] are present in these areas. (f) DAU3 group, grade 4: extensive fibrosis [arrows] in areas of toxic nephropathy with degenerations and tubular necrosis. (g–i) Representative photomicrographs of hepatic damage. (g) DOX2 group, grade 1: initial damage of the liver. Some hepatocytes show diffuse vacuoles inside cytoplasm []. (h) DAU3 group, grade 4: hepatocytes revealed an extensive toxic damage. Necrotic hepatocytes are present [N] and abundant hepatocytes show numerous and extensive vacuoles inside cytoplasm []. (i) DAU3 group, grade 4: diffuse fibrosis [arrows] in areas with necrotic hepatocytes. (a-b), (d-e), and (f-g): haematoxylin and eosin; (c), (f), and (i): Masson’s blue trichrome.

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