Cardiomyopathy in rats with Walker 256 tumor: The potential role of microvascular disease in its genesis

Abstract Considering that diffuse abnormalities of myocardial microcirculation with transient ischemia have been suggested to play a role in the genesis of myocytolytic necrosis, characteristic lesion of dilated or congestive cardiomyopathies, and the bloodstream is the most common pathway for dissemination of cancer cells, which gain access to the microcirculation, the present study was undertaken to search for morphologic and electrocardiographic evidence of myocardial damage associated with microcirculatory disease in rats experimentally inoculated with the Walker 256 tumor. Young albino rats inoculated intramuscularly with the Walker 256 tumor developed a cardiomyopathy characterized by diffuse small foci of myocytolytic necrosis, decreased thickness of the mean left midventricular wall associated with reduced size of the minor diameter of myocytes, and electrocardiographic abnormalities reflecting the myocardial damage, correlated with the presence of a microvascular disease, characterized by intramyocardial microvessels (less than 50 μm in diameter) partially or totally occluded because of entrapment of tumor cells and fibrin-platelet/tumor cell-cellular debris thrombi. The occlusive or subocclusive small vessel lesions preceded the development of the myocytolytic necrosis, suggesting that the microvascular disease would play an important role in the process of focal micronecrosis and consequent electrocardiographic changes. However, it must be taken into account that the tumor thromboemboli can generate related factors that could promote cell injury and cell death. In conclusion, the hematogenic dissemination of Walker 256 cells promotes the development of an experimental cardiomyopathy attributable, at least in part, to microvascular obliterative changes in the myocardium.