Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of non-reperfused myocardial infarction.

In patients with myocardial infarction (MI), cardiac rupture is an uncommon, but catastrophic complication. In the mouse model of non-reperfused MI, reported rupture rates are highly variable, and depend not only on the genetic background and sex of animals, but also on the method used for documentation of rupture. In most studies, diagnosis of cardiac rupture is based on visual inspection during autopsy; however, criteria are poorly defined. We performed systematic histopathologic analysis of whole hearts from C57BL6J mice dying after non-reperfused MI, and evaluated the reliability of autopsy-based criteria in identification of rupture. Moreover, we compared the cell biological environment of the infarct between rupture-related and rupture-independent deaths. Histopathological analysis documented rupture in 50% of mice dying during the first week post-MI. Identification of a gross rupture site was highly specific, but had low sensitivity; in contrast, hemothorax had high sensitivity, but low specificity. Mice with rupture had lower myofibroblast infiltration, accentuated macrophage influx, and a trend towards reduced collagen content in the infarct. Male mice had increased mortality and higher incidence of rupture. However, infarct myeloid cells harvested from male and female mice at the peak of the incidence of rupture had comparable inflammatory gene expression. In conclusion, the reliability of autopsy in documentation of rupture in infarcted mice is dependent on the specific criteria used. Macrophage-driven inflammation and reduced activation of collagen-secreting reparative myofibroblasts may be involved in the pathogenesis of post-MI cardiac rupture.