Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in rats.
OBJECTIVE
Partial portal vein ligation (PPVL) is a commonly used procedure to induce prehepatic portal hypertension in animal models. The aim of this study was to test the hypothesis that the hepatic arterial flow becomes the primary source feeding the sinusoids in the liver after PPVL.


METHODS
Sprague-Dawley rats underwent either sham operation or partial portal vein ligation (PPVL). The number of vessels in the liver at 2 weeks postoperatively was determined by factor VIII immunolocalization and the gene expression of angiogenic factors was assessed by RT-PCR. The total hepatic arterial supply to the liver was measured using the fluorescent microsphere injection technique. To further test the hypothesis, two additional groups of rats underwent hepatic artery ligation (HAL) or PPVL plus HAL (PPHAL). The integrity of hepatic microcirculation was then evaluated in all four groups by intravital microscopy.


RESULTS
At 2 weeks after operation, the number of vessels detected by factor VIII staining was significantly higher in PPVL compared to sham. Densitometric analysis of RT-PCR bands revealed a significant increase of vascular endothelial growth factor gene expression in PPVL compared to sham. Arterial flow to the liver measured by fluorescent microspheres was increased by 190% in PPVL compared to sham. When all four groups were compared, no prominent histological abnormality was observed in sham, HAL, and PPVL groups; however, PPHAL livers showed focal necrosis and inflammatory cell infiltration around the portal triads. Additionally, only the PPHAL livers showed a decreased sinusoidal diameter and significantly lower perfusion index (PPHAL 42.9+/-6.1; sham 85.7+/-7.0, PPVL 80.2+/-6.5, HAL 70.9+/-4.5).


CONCLUSIONS
These results suggest that the hepatic artery flow becomes the primary source for the blood supply of sinusoids and the compensatory change in the hepatic arterial system plays a critical role in maintaining microcirculatory perfusion following the restriction of the portal vein flow by PPVL.
Yokoyama
Yukihiro
Y
Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
Wawrzyniak
Andrew
A
Sarmadi
Amir M
AM
Baveja
Rajiv
R
Gruber
Helen E
HE
Clemens
Mark G
MG
Zhang
Jian X
JX
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005169:Factor VIII / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006499:Hepatic Artery / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008026:Ligation / Q000009:adverse effects; D008102:Liver Circulation / Q000502:physiology*; D011169:Portal Vein / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D005169:Factor VIII; D004247:DNA