BACKGROUND: The hypertrophic growth of the heart was seen as "compensatory" and hence beneficial. However, the Framingham Heart Study showed that left ventricular hypertrophy is a marker for an increased risk of adverse cardiovascular events. We examined the morphological and functional effects of volume overload on the heart by aortocaval fistula(ACF). METHODS: Female C57/BL6 mice weighting 23-25 g were anesthetized with ketamine(100 mg/kg) and xylazine(5 mg/kg). After abdominal incision, the aorta was punctured with a needle and the needle was further advanced into the vena cava. After withdrawal of the needle, the aortic puncture site was closed with a 10/0 nylon suture. The patency of the shunt was visually verified as mixing of venous and arterial blood in the vena cava. RESULTS: Four weeks after shunt induction, mice showed a significant cardiac hypertrophy. The heart/body weight ratio increased from 0.38짹0.01% in control to 0.76짹0.06% in ACF groups. The pathology of the hearts showed that cardiac fibrosis in ACF groups along with a decrease in PECAM-1 and increase in the number of apoptotic endothelial cells and thrombospondin-1 expression(P<0.05). CONCLUSION: The ACF in the mouse constitutes a new model of overt congestive heart failure. The cardiac hypertrophy by volume overload may compromise microvascular homeostasis with increased apoptosis and fibrosis in myocardium. Figure. Myocardial immunohistochemical staining for trichrome(A,B), CTGF(C,D), thrombospondin(E,F), TUNEL(G,H) in the heart in ACF(A,C,E,F) and control mice(B,D,F,H).