The high incidence of atrial thrombosis in mice given doxorubicin.
Doxorubicin (DX)-treated mice represent an animal model for studying new drugs for heart disease. Coincidentally, in the collection of damaged myocardial tissue, thrombosis was detected in the atrium. The incidence reached 75% in mice given 4 mg/kg DX iv 10 times. They were white thrombi consisting of the fibrin, platelets, and neutrophils. Cardiac muscle damage was more prominent in the atria than in the ventricles. Light microscopically, vacuolization and degeneration of atrial myocytes and interstitial inflammatory cell infiltration were observed. Electron microscopy revealed dilatation of the sarcoplasmic reticulum and an increase in number of normal and/or degenerate mitochondria. Inflammation extended from the cardiac muscle to the endocardium. The cause of atrial thrombosis in DX-treated mice is unknown but may relate to endocardial damage and changes of blood flow in the atrium secondary to cardiac muscle damage. DX-treated mice could serve as an experimental animal model for the evaluation of efficacy and toxicity of antithrombotic or antiplatelet drugs.
Fujihira
S
S
Department of Pathology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Yamamoto
T
T
Matsumoto
M
M
Yoshizawa
K
K
Oishi
Y
Y
Fujii
T
T
Noguchi
H
H
Mori
H
H
D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced*; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000166:cytology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013927:Thrombosis / Q000139:chemically induced*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D004317:Doxorubicin