Intravital analysis of microcirculation in the regenerating mouse liver

Abstract

Background: Liver tissue remodeling after surgery includes development of new hepatic microvasculature. Although various endothelial growth factors have been shown to play a role in liver tissue repair, the functional consequences of rapid endothelial cell proliferation are unknown. To determine the influence of endothelial cell proliferation on vessel functionality, we have analyzed the in vivo morphology of microvasculature in the regenerating liver.

Materials and methods: Mice were subjected to 70% partial hepatectomy (PH) and at 24, 48, 96 h, 7 and 14 days post PH underwent intravital microscopy of the exposed liver remnant. Intrahepatic microvessels were visualized with fluoresceine-labeled dextran. Recorded parameters were: functional vessel length (VL), functional vessel diameter (VD), hepatic cell plate width (PW), and functional vessel surface area (FVSA).

Results: VL showed a transient decrease (17-31%) after PH. PW was significantly increased in the regenerating liver. VD significantly increased on days 1 and 2 post PH. On days 4, 7, and 14, VD returned to normal. In contrast, FVSA remained within normal range until day 14 post PH.

Conclusions: Despite changes in vessel length and hepatic cell plate width in the early regenerating liver, functional vessel surface area remains normal until day 14 post PH. These changes may indicate compensatory vascular growth mechanisms to ensure adequate hepatocyte perfusion during liver regeneration. Better understanding of functional variations during physiological liver regeneration may be of use in liver conditions characterized by defective regeneration, e.g., cirrhosis.