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Aim: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely small-for-size liver transplantation in pigs., Methods: The right lateral lobe of pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated., Results: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt, eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2+/-26.9 mL/min/100 g liver tissue and 270.5+/-72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2+/-27.8 mL/min/100 g liver tissue and 42.7+/-32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt., Conclusion: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

We investigated the effects of portocaval shunt (PCS) on excessive portal flow in producing sinusoidal microcirculatory injury in small-for-size liver transplants in pigs. The posterior segment of a whole liver (25%) was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS (n = 11), and group B, graft without PCS (n = 11). The PCS was a side-to-side anastomosis of the portal vein and the inferior vena cava. In group A, eight pigs survived for more than 4 days; all pigs except for one died of graft nonfunction within 24 hours in group B. The portal flow after reperfusion decreased in group A, but increased about three times greater in group B than that before the operation (P < .01). In group B, destruction of the sinusoidal lining and bleeding in the periportal areas were observed after reperfusion, findings that were not recognized in group A. These results suggest that graft nonfunction after small-for-size liver transplantation may be attributable to excessive portal flow producing sinusoidal microcirculatory injury.

An effective way to overcome shortage of donors in liver transplantation (LTx) is to consider such from non-heart-beating donors (NHBDs). We investigated how a liver graft should be treated before and/or after procurement for successful LTx from an NHBD. Porcine LTx was performed with FR167653 (FR), a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and/or prostaglandin E(1) (PG). Animals were allocated to an FR group (n=4, donors and recipients were treated with FR), a PG group (n=4, donors and recipients were treated with PG), or an FRPG group (n=4, donors and recipients were treated with both FR and PG). No recipients in the FR group and only two of four recipients in the PG group survived, whereas all recipients in the FRPG group survived. Suppression of TNF-alpha and IL-1beta and maintenance of microcirculation are the key to successful transplantation from NHBDs.

To evaluate the age-related response of essential cell functions against peroxidative damage in hyperthermia, we studied the biochemical response to heat stress in both young and aged rats. Passive hyperthermia was immediately observed in rats after exposure to hot environments. In aged rats, the rectal temperature maintained thermal homeostasis and increased to the same degree as in young rats. In these aged animals, the damage from heat stress was more serious than in young animals. In aged rats under normal environmental conditions, hepatic cytosolic glutathione peroxidase (GSH peroxidase) activities were markedly higher than those activities in younger rats. Hepatic cytosolic GSH peroxidase activities were induced by heat stress in young rats but were decreased by hot environments in aged rats. Hepatic catalase activities in young rats were not affected by hot environments, whereas in aged rats, hepatic catalase activities were seriously decreased. Catalase activities in the kidney of aged rats were also reduced by hot environments. Lipid peroxidation in the liver was markedly induced in both young and aged rats. Because the protective enzymes for oxygen radicals in aged rats were decreased by hot environments, lipid peroxidation in the liver was highly induced. In aged rats, lipid peroxidation in intracellular structures such as mitochondria and microsomes was also markedly induced by hot environments. In both young and aged rats, hyperthermia greatly increased the development of hypertrophy and vacuolated degeneration in hepatic cells. In aged rats, both mitochondria and endoplasmic reticulum of the hepatic cells showed serious distortion in shape as a result of exposures to hot environments. Microsomal electron transport systems, such as cytochrome P450 monooxygenase activities, were seriously decreased by heat stress in aged rats but not in young rats. Although the mitochondrial electron transport systems were not affected by acute heat stress in young rats, their activities were simultaneously inhibited after long-lasting heat exposure. In isolated hepatic cells and polymorphonuclear leukocytes in animals, the 70-kDa heat shock-induced proteins were markedly increased by heat stress. In conclusion, the heat stress-inducible oxygen radical damage becomes more severe according to the age of rats. Because aging and hyperthermia have a synergistic effect on lipid peroxidation, protective enzyme activities for oxygen radicals may be essential for surviving and recovering from thermal injury in aged animals and also in humans.

Changes in amino acids in liver tissue during hemorrhagic shock were examined in eight mature mongrel dogs using the microdialysis method. The mean blood pressure was maintained at 50 mmHg by exsanguination, and the values of liver tissue amino acids after 30 minutes showed significant decreases of aspartate, glutamate, histidine, glutamine, glycine and taurine. The decrease of taurine was especially marked. The values dropped further 30 minutes after returning the blood into circulation with some exceptions. These results suggest the possibility that hemorrhagic shock causes reduction in uptake of amino acids by the liver or consumption of amino acids in the liver, and that bile acid metabolism appears to be disturbed by the marked drop in the taurine level. It is necessary to give careful consideration to the possible existence of reduced amino acid metabolism in the liver in the treatment of hemorrhagic shock.