Microcirculatory blood flow during liver regeneration after partial hepatectomy in LPS-sensitive and insensitive mice: an IVFM study

Background objective: Haemodynamic events and the changes to hepatic blood flow are the least studied and least understood aspects in liver regeneration. It has been previously reported that liver regeneration is delayed in C3H HeJ mice, a mouse that is hypo-responsive to lipopolysaccharide (LPS), due to a point mutation in trl4 gene. Using IVFM, we aimed to determine whether delayed liver regeneration in these LPS-insensitive mice was associated with altered hepatic microcirculation during liver regeneration. Methods: The hepatic microcirculation of the regenerating liver of C3H HeN (normal, LPS-sensitive) or C3H HeJ (LPS-insensitive) mice was studied using intravital fluorescence microscopy (IVFM), at days three and seven after hepatectomy. Results: Liver mass restoration was significantly delayed in C3H HeJ mice at all time points after PH compared to C3H HeN mice. At day 3 after PH, sinusoidal red blood cell (RBC) velocity increased by 100% in C3H HeN but only by 40% in C3H HeJ mice (P lt;0.001). Estimated sinusoidal blood flow increased by 50% and 70% at days 3 and 7 after PH respectively in C3H HeN mice. In contrast, estimated sinusoidal blood flow was similar to the control group in C3H HeJ mice at day 3 and was lower by 20% at day 7 after PH. Sinusoidal diameter and functional sinusoidal density were reduced by 20% at day 3 post-hepatectomy in both strains. Conclusion: The present study indicates that hepatic blood flow might play a pivotal role in liver regeneration. Altered sinusoidal blood flow and velocity in the LPS-insensitive mice may contribute to the delay in regenerative response in these mice.