Kageyoshi Seino

The effects of intraportal prostaglandin E1 administration on hepatic warm ischemia and reperfusion injury in dogs.

To determine the route of prostaglandin E1 (PGE1) administration which would have the greatest protective effect against hepatic warm ischemia, two experiments were performed using dogs. The pharmacokinetics of PGE1 were investigated in a preliminary study, after which, the effects of PGE1 in a 90-min warm ischemic liver model were examined. The dogs were divided into three groups of ten, according to the treatment given: group A was an untreated control group, group B received PGE1 intravenously, and group C received PGE1 intraportally. The PGE1 was infused continuously at a rate of 0.02 μg/kg/min before and after ischemia. All the dogs in groups A and B died within 24 h of induced ischemia. Whereas, six of the ten dogs in group C survived for over 3 days. The arterial ketone body ratio was not maintained in groups A and B, but it was in group C. Furthermore, in group C the serum lipid peroxide level, which reflects hepatocellular membrane damage, was maintained at a lower level than that in the other groups after ischemia. Electron microscopy revealed sinusoid destruction and changes in both the plasma membrane and parenchymal cell mitochondria in groups A and B, while in group C these structures were well preserved. These findings confirmed that intraportally administered PGE1 improved the hepatic microcirculation and stabilized the hepatocellular membranes. Our results indicate that intraportal administration of PGE1 has a greater protective effect than intravenous administration against warm ischemic liver injury.

Three-stage total hepatectomy using a portocaval shunt tube in rats.

Male Wistar rats (CLEA Japan, Inc., Tokyo, Japan) weighing 230 to 300 g were housed in metal cages with controlled light and dark cycles. They were fed standard rat chow until 24 hours before each operation, at which time they were given free access only to water. Total hepatectomy was performed as a three-stage procedure under clean conditions. The study protocols complied with the Guidelines for Animal Experimentation, Hirosaki University, for human care of experimental animals.

The effect of intraportal PGE1 on warm ischemic liver damage

To determine the most effective route of administering prostaglandin E1 (PGE1) to inhibit warm ischemic liver damage, 90-min warm ischemia was established in a canine model. The dogs were divided into three groups according to the treatment given. Thus, group A (n = 10) was the control group which received no treatment, group B (n = 7) was administered PGE1 intravenously, and group C (n = 7) was administered PGE1 intraportally. PGE1 was continuously administered before and after the ischemia at a rate of 0.02μ⦰/min. The branched-chain amino acid to aromatic amino acid ratio in the hepatic vein, and the arterial ketone body ratio of acetoacetic acid to β-hydroxybutyric acid, were examined to observe the metabolism of each amino acid and the oxidation-reduction ability of hepatocytes. Both ratios were maintained only in the group C dogs, three of which survived for over 3 days, whereas in groups A and B, all the dogs died within 24h. The results of this study imply that the intraportal administration of PGEI was more effective against warm ischemic liver damage than the intravenous administration of PGE1.

Effect of intraportal prostaglandin E1 administration on warm ischemic liver damage in the dog

Abstract To evaluate the effect of intraportal administration of prostaglandin E 1 (PGE 1 ) on warm ischemic liver damage, two experimental studies were designed using dogs. First as a preliminary study (Expt. 1), the portal blood flow and PGE 1 concentration in blood obtained from the portal vein and femoral artery were measured for each of portal and peripheral venous administration of PGE 1 at a rate of 0.02 μg/kg/min. When PGE 1 was administered via the peripheral vein, little PGE 1 reached the liver, although portal blood flow was increased. Then, to determine the most effective route of PGE 1 administration to prevent 90-min warm ischemic liver damage, dogs were divided into the following three groups (Expt. 2): a PGE 1 -untreated (control) group (group A, n = 10 ), a peripheral venous PGE 1 -administered group (group B, n = 7 ) and an intraportal PGE 1 -administered group (group C, n = 7 ). PGE 1 was continuously infused before and after the ischemia at the rate of 0.02 μg/kg/min. The arterial ketone body ratio (acetoacetic acid/β-hydroxybutyric acid; AKBR) as well as the concentration of endotoxin (Etx) were measured. In both groups A and B, all the dogs died within 24 h. However, in group C, three out of the seven dogs survived and were sacrificed on the 3rd day. One dog died within 24 h, and the other three died within the next 2 days. The AKBR values were decreased after ischemia in all groups, but only in group C, this value recovered to the initial level. The Etx concentration increased in the early phase after ischemia in all groups, but in group C it started to decrease immediately after ischemia. The above results indicate that intraportal administration of PGE 1 provides a more protective effect than peripheral venous administration against warm ischemic liver injury.