Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis

Abstract

The aim of the present study was to investigate the effects of hepatic blood inflow on liver function, liver ultrastructure and the regeneration of future liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A rat model of cirrhosis was established through intraperitoneal injection of carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and different blood inflow models by portal vein (PV) and/or hepatic artery (HA) stenosis were conducted on the cirrhosis rats. Animal models were constructed as follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV + low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV + low-flow HA (group E). Hepatic blood inflow was detected by laser speckle contrast analysis, liver function and pathological changes were analyzed, Masson staining was used to identify the fibrosis of the liver and Periodic acid-Schiff staining was used to identify glycogen synthesis and hepatocyte function. The liver cell ultrastructure was evaluated by transmission electron microscopy, and the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to determine the regeneration of the FLR. Five days after major hepatectomy and liver blood inflow modulation, pathological examination of the livers from groups B and C revealed less congestion and less extensive hepatocellular injury. The serum alanine aminotransferase level of group B at 1, 3 and 5 days after hepatectomy and blood inflow modulation was 460.9±31.7, 331.0±22.0 and 285.6±15.8 U/l, respectively (control group: 676.9±41.7, 574.9±28.0 and 436.1±32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3 and 5 days was 20.4±1.5, 16.1±1.0 and 13.5±0.6 µmol/l, respectively (control group: 30.3±1.4, 26.5±0.8 and 22.1±1.2 µmol/l, respectively; P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups increased significantly and the mitochondrial swelling was alleviated. The positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9±3.6, 15.7±2.3 and 12.9±2.4%, respectively (control group: 10.1±2.1%, P<0.05), and the positive rate of Ki-67 in group E was 6.1±1.4% (compared with that of the control group, P<0.05). The remnant liver weight of group B was 15.4±1.0 g (compared with that of the control group, P<0.05). Therefore, decreased portal blood flow combined with increased hepatic arterial blood flow alleviated the congestion in the liver following major hepatectomy in cirrhotic rats, improved the pathological status and liver function, increased the expression of Ki-67 and promoted liver regeneration.

Assessment of Fibrotic Liver Regeneration After Partial Hepatectomy With Intravoxel Incoherent Motion Diffusion-Weighted Imaging: An Experimental Study in a Rat Model With Carbon Tetrachloride Induced Liver Injury

“…These findings were consistent with a previous animal study (Chow et al, 2012), the decrease of D * values resulted from the alteration in liver perfusion during the progression of liver fibrosis. Post-PH, the results clearly showed decreased liver D * values on day 1 and then gradual recovery in controls, but a continuous increase of liver D * values in the fibrosis group, findings consistent with previous studies (Harkness, 1952;Jin et al, 2018). The opposing changes in liver D * values between control and fibrotic livers in the early stage post-PH might result from the different microstructure and response of residual liver to PH.…”

“…Harkness (1952) found that residual liver was much paler than control livers up to 48 h post-PH, and liver blood space decreased to a minimum at 48 h, followed by a gradual increase after a 67% hepatectomy in control livers. Jin et al (2018) found liver blood flow increased on day 1 and then decreased on day 5 after 45% PH by laser speckle contrast analysis in cirrhotic livers. However, those methods were invasive.…”

Fluid dynamics analyses of the intrahepatic portal vein tributaries using 7-T MRI

“…In humans, Doppler ultrasound has been the standard modality for this purpose; 10 yet it often yields incomplete or inaccurate hemodynamic data due to the limited size of acoustic windows, which can be compounded by overlying gas-filled bowels, 11 observer variability, 12 the difficulty of visualizing complex PV branches, 11 and the inability to measure three-dimensionally-variable flow using a 2D scanning technique. In small animals, flow meters, [13][14][15] lase specs, 16 and microspheres, 17,18 have been used to evaluate PV flow, but these modalities are too invasive to be used repeatedly, and the flow velocity data they provide is insufficiently detailed. Alternatively, several studies have used MRI to evaluate PV flow in humans and rodents, 19,20 concluding that MRI offers several advantages over the aforementioned modalities, including noninvasiveness, objectivity as opposed to examiner dependence, and a three-dimensional scanning area.…”

Liver Transplantation

“…Seventy-five percent of the total hepatic flow is provided by the portal vein, which provides 50-70% of hepatic nutritional requirements [186]. Interplay between the portal and hepatic inflow has significant impact on hepatic regeneration [187]. This is especially true after orthotopic LT and even more so for LDLT.…”