Shuntaro Koyama

Acute Portal Hypertension Reflecting Shear Stress as a Trigger of Liver Regeneration Following Partial Hepatectomy

The concept of injury in liver regeneration after partial hepatectomy (PHx), and the reason hepatocytes that have not been directly injured regenerate, remain unclear. It is known that shear stress resulting from blood flow plays an important role in the mechanism of remodeling blood vessels, and portal pressure reflects shear stress. This study was conducted to determine whether acute portal hypertension (APH) can become a trigger of liver regeneration as shear stress following PHx in a rat model. Portal pressures became elevated immediately after 70% and 90% PHx, peaking on postoperative day (POD) 3, and thereafter decreasing in proportion to the diminution of liver regeneration. The portal pressures after 90% PHx were significantly higher than those after 70% PHx even on POD 7, while those of the portocaval (PC) shunt groups decreased following PC shunting both with and without 70% PHx. The liver/body weight (LW/BW) ratio also decreased in the PC shunt both with and even without 70% PHx. The gradient expressions of class I antigen on sinusoidal endothelial cells (SEC) were found only in the periportal area, which has the highest portal pressure in the healthy rat liver. However, after hepatectomy these expressions were detected from the periportal area to the central venous area. These results suggest that APH as shear stress following PHx may not only become a trigger of hepatocyte regeneration, but also of SEC regeneration, and that surplus APH induces liver dysfunction.

Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs.

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E1 (PGE1) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE1 at 0.2 μg/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE1 was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE1 is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.

Enhanced liver regeneration in rats treated with 15-deoxyspergualin alone and in combination with FK 506

SummaryThe effects of 15-deoxyspergualin (DSG) alone and in combination with FK 506 (FK) on liver regeneration after 2/3 hepatectomy was studied. The administration of 5 mg/kg DSG increased the liver weight as a percentage of the body weight (RLW) in the 5 days following the hepatectomy. This enhanced regeneration was not affected if interleukin(IL)-2 was also given. The combination of 1 mg/kg DSG and 0.05 mg/kg FK induced the highest values for RLW. The amounts of food and water intake increased in the DSG and FK combined group. Blood chemistry indicated that the combined administration of DSG and FK could reduce side-effects more effectively than separate administration. These observation led us to conclude that DSG has a stimulating potency in liver regeneration by means of direct supression of T cell activation, and there is a synergistic effect on regeneration by DSG and FK.

Pathophysiology of malabsorption syndrome

ConclusionAs the results of a study on the pathophysiology of steatorrhea from the point of view of gastrointestinal hormones, it was suggested that gastrointestinal hormones, as yet unidentified, particularly gastrin and G/S ratio played a role in the pathogenesis of steatorrhea in patients with Zollinger-Ellison syndrome. The patients with group I and III pancreatitis showed a similar pattern, and a few new findings were achieved.