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Biomedical subjects

Y Shimahara

Publications and source records attributed to Y Shimahara.

At least 73 records · Page 4Linked to original sources

Total vascular exclusion for hepatic resection in cirrhotic patients. Application of venovenous bypass.

Hepatic vascular exclusion with double venovenous bypass using a centrifugal force pump was used in major hepatic resections in eight patients with hepatocellular carcinoma combined with cirrhosis, and results were compared with those in four patients with hepatocellular carcinoma without cirrhosis and eight with metastatic tumors without cirrhosis among 521 patients undergoing liver resection. Concomitant resection of the retrohepatic inferior vena cava was performed in three of eight patients with cirrhosis and five of 12 patients without cirrhosis. All patients, except one with cirrhosis, tolerated major resection without any hemodynamic impairment, which is often observed in hepatic vascular exclusion without venovenous bypass. One patient, whose complete inflow occlusion period was 70 minutes, died of liver failure. In this patient, the recovery of the arterial ketone body ratio above 1.0 was delayed until 3 days after recirculation, whereas the ratio in the others recovered promptly. Postoperative complications such as increased bilirubin level, pleural effusion, and gastrointestinal tract bleeding were observed in seven of eight patients with cirrhosis compared with six of 12 without cirrhosis. Hepatic vascular exclusion is feasible even in cirrhotics as long as it is applied with venovenous bypass and is kept within the time limit of 60 minutes.

Adult↗

Bone metastases of hepatocellular carcinoma after liver resection.

Between January 1985 and July 1990, 323 cases of hepatocellular carcinoma underwent liver resection in our department. Bone metastases were found in 12 of these cases (3.7%). Bone metastases were mainly found in vertebral bone (58.3%) and pelvic bone (41.7%). The time interval to the development of bone metastasis after liver resection was closely related to the presence of intrahepatic metastasis and the stage at operation. In all cases, the initial clinical symptom was pain and/or motor disturbance. Radiotherapy was performed in 10 cases and transcatheter arterial embolization or surgery was performed in 4 cases. The pain or neurological symptoms improved with these therapies in all cases. Cumulative survival was 1 year in 74%, 2 years in 34%, and 3 years in 17%, respectively.

Adult↗

Clinical application of arterialization of portal vein in living related donor partial liver transplantation.

Arterialization of the portal vein was employed during hepatic arterial reconstruction in our first few clinical experiences of partial liver transplantation using liver grafts obtained from living related donors. This procedure reduced the time required for revascularization of the grafts to about 25 min, and could in fact reduce the ischemic phase of the grafts. Repeated practice of the clinical transplantation technique has shortened the time needed to complete vascular reconstruction, eliminating the need for this procedure in most of our subsequent cases. In many clinical cases, however, there may be emergency situations which require vascular reconstruction, resulting in a prolongation of ischemic phase and the deterioration of the cellular viability of the graft. In such situations, arterialization of the portal vein can be a useful way to prevent the prolongation of the ischemic phase and to rescue the graft.

Arteriovenous Shunt, Surgical↗

Receiver operating characteristic (ROC) analysis of the ability of arterial ketone body ratio to predict graft outcome after liver transplantation--its sensitivity and specificity.

To evaluate the ability of arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) to predict graft prognosis after liver transplantation, the diagnostic value as a predictive index was compared between AKBR and conventional liver function tests using receiver operating characteristic (ROC) analysis. The ROC curves were determined for AKBR, GOT, GPT, total bilirubin, serum lactate level, and prothrombin time, all of which were measured on the 1st and 2nd postoperative days in 88 cases of liver transplantation. Comparisons of the areas under the ROC curves between AKBR and other tests revealed the significant superiority of AKBR to other tests in predicting graft death within 1 month after transplantation. The present study suggests that AKBR can be used as an accurate index to predict graft prognosis after liver transplantation.

Adolescent↗

Impaired energy metabolism of lymphocytes in cirrhotics after hepatectomy.

To clarify the mechanism of high susceptibility to infection in cirrhotics, the changes in adenylate energy charge and MTT assay in peripheral blood lymphocytes were studied in cirrhotic and noncirrhotic patients in the early postoperative period after hepatectomy. The adenylate energy charge measured by radioactive labeling of the lymphocyte adenine nucleotide pool showed no significant difference preoperatively between cirrhotics and noncirrhotics, but a significant difference was observed in the pre- and postoperative distribution of adenine nucleotide metabolites (P less than 0.01). In the cirrhotic group, the adenylate energy charge of lymphocytes decreased significantly to 0.807 +/- 0.011 on the third postoperative day compared with preoperative value (0.891 +/- 0.006, P less than 0.01) and was restored to the normal range on the fifth and tenth postoperative days (0.886 +/- 0.006, 0.899 +/- 0.014), while no significant decrease was observed in the noncirrhotic group. MTT assay revealed that lymphocyte cell function decreased significantly in cirrhotics after hepatectomy. These results indicate that, in cirrhotic patients, the energy metabolism of lymphocytes is already impaired to some extent preoperatively, and that it undergoes further deterioration when surgical stress is applied. It is suggested that the decreased energy metabolism in the lymphocyte may be responsible for the increased susceptibility to infection in postoperative cirrhotics.

Adenosine Diphosphate↗

A mixture of nucleosides and a nucleotide alters hepatic energy metabolism 24 hours after hepatectomy in rabbits.

The effect of administering a nucleoside-nucleotide mixture on hepatic energy metabolism was evaluated at 24 h after hepatectomy in rabbits that had had 70% of their livers removed. After hepatectomy, animals were administered continuous intravenous infusion of 2 mL/(kg body wt-h) of 9 g/L NaCl (Group S), 5.99 mmol/L nucleoside-nucleotide mixture (Group N1) or 11.98 mmol/L nucleoside-nucleotide mixture (Group N2). At 24 h after hepatectomy, the hepatic adenylate energy charge in Group S (0.83 +/- 0.01, mean +/- SEM) was significantly lower than that before hepatectomy (0.90 +/- 0.01). By contrast, the values in Groups N1 and N2 after hepatectomy (0.74 +/- 0.04 and 0.73 +/- 0.04, respectively) were significantly lower than that in Group S. The hepatic mitochondrial phosphorylation rate before hepatectomy was 46.40 +/- 4.88 nmol ATP/(mg mitochondrial protein-min). After hepatectomy, significantly greater values were observed in Groups N1 and N2 (69.53 +/- 7.20 and 63.31 +/- 6.11, respectively), yet those values were less than observed in Group S (109.14 +/- 4.80). These results suggest that the nucleoside-nucleotide mixture suppressed the enhancement of hepatic mitochondrial phosphorylative activity at a time when hepatic adenylate energy charge is compromised. Such enhancement is needed to compensate for the increased energy expenditure due to surgical intervention.

Adenosine Diphosphate↗

An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors.

The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506.

Adolescent↗

Beneficial effect of combined 3,5,3'-triiodothyronine and vasopressin administration of hepatic energy status and systemic hemodynamics after brain death.

The influence of combined replenishment of L-3,5,3'-triiodothyronine (T3) and vasopressin (antidiuretic hormone [ADH]) on both hepatic metabolism and systemic hemodynamics was assessed in brain-dead dogs. Arterial ketone body ratio (AKBR) was measured as a parameter of hepatic metabolism, which reflects the redox state (free nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide) of liver mitochondria. Mean arterial blood pressure (MAP) was significantly decreased from 110.4 +/- 3.8 to 44.4 +/- 1.7 mmHg, at 1 hr after completion of brain death (P less than 0.01). In the control group AKBR was maintained thereafter at near control value of 1.0 with a significant decrease in serum lactate concentration in spite of marked hypotension. T3 infusion at a rate of 1 microgram/kg/hr elevated the AKBR but did not elevate MAP. Vasopressin infusion at a rate of 0.1 U/kg/hr sustained AKBR and elevated MAP significantly at 1 hr after administration but tended to decrease thereafter. Combined administration of T3 and ADH elevated the AKBR to about 2.0, and MAP was restored to near-normal level. Other parameters such as glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactic dehydrogenase, reflecting liver cell injury and serum creatinine, and blood urea nitrogen as renal function, were maintained within normal range. These results indicate that combined T3 and vasopressin administration has a beneficial synergistic effect on both hepatic energy metabolism and systemic hemodynamics without any detrimental influence to other conventional parameters. Therefore, it is suggested that this combined administration may contribute to the management of potential multiorgan donors.

Animals↗

Analyses of the risk and operative stress for donors in living-related partial liver transplantation.

Operative risk and stress were analyzed in 28 parent-donors whose children received partial liver transplantations at the Second Department of Surgery, Kyoto University Hospital between June 1990 and December 1991. Graft-harvesting operations were classified into three types: left lobectomy (group L, n = 12), left lateral segmentectomy (group S, n = 15), and right lobectomy (n = 1). Since donor safety is a primary concern, great care was taken to minimize potential damage to the remaining lobes of the donor liver as well as the graft liver by avoiding stressful maneuvers such as hepatic vascular clamping during the transection of the hepatic parenchyma. In all cases the arterial ketone body ratio, which reflects the hepatic mitochondrial redox potential, was maintained at over 0.7 throughout the donor operation as well as postoperatively. There was no significant difference in the postoperative RBC, WBC, serum GOT, and total bilirubin between groups L and S, although the abnormalities exhibited by the single right lobectomy case tended to be larger and more prolonged. All cases were within the range acceptable for immediate discharge, and all donors of groups L and S were subsequently discharged within 14 days without any postoperative complications. The single right lobectomy donor was discharged on POD17 because of transient slight icterus, which is the only postoperative complication encountered in this series thus far. The present analyses would indicate that the risk and operative stress to the donor in living-related partial liver transplantation can be minimal when the left lobe or left lateral segment of the liver is used for the graft.

Aspartate Aminotransferases↗

Evaluation of ketogenesis in seriously reduced hepatic mitochondrial redox state. An analysis of survivors and non-survivors in critically ill hepatectomized patients.

Ketogenesis was evaluated in 33 critically ill hepatectomized patients in relation to the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate), which reflects hepatic mitochondrial redox state. In 15 patients whose arterial ketone body ratio decreased to below 0.4, blood ketone body levels were significantly increased concomitant with marked increase of blood lactate and plasma alanine levels. In the 6 survivors of these 15 patients, the arterial ketone body ratio was restored within the next 2 days, and blood ketone body levels were decreased. By contrast, in the nine non-survivors, the arterial ketone body ratio remained below 0.4, and blood ketone body levels were decreased, accompanied by significant increases in blood lactate and plasma alanine levels in the terminal stages. These results suggest that ketogenesis acts as an alternative process for ATP synthesis in the liver in critically ill patients. Death occurs when the liver falls into an energy crisis concomitant with the cessation of ketogenesis.

Adult↗

[Diabetes mellitus as a risk factor in major hepatic resection and its strategy by intraportal insulin administration].

Diabetes mellitus, or insulinopenia, is a possible risk factor in major hepatic resection, because insulin is a typical hepatotrophic factor governing hepatic mitochondrial function. By analyzing 91 hepatic resections for hepatocellular carcinoma, we made a multiple regression equation for prediction of postoperative mortality using insulinogenic index (II) and redox tolerance index (RTI) which were both calculated by measuring insulin level and arterial ketone body ratio during oral glucose tolerance test (z = 3.11 x II + 1.43 x RTI - 2.27). When z was negative, the mortality rate was 33.3% in major hepatic resection cases. Since 1990, we have prospectively applied intraportal insulin administration (IIA) therapy as postoperative management to patients with negative z score. In the total 19 patients the postoperative mortality was significantly reduced by the introduction of IIA therapy. Hence, the IIA therapy can be a strategy against diabetes mellitus as a risk factor in major hepatic resection.

Aged↗

Decrease in arterial ketone body ratio indicating graft dysfunction after liver transplantation.

In 3 cases of living related liver transplantation, arterial ketone body ratio (AKBR) showed secondary decrease in the early postoperative period, indicating the graft dysfunction more rapidly and sensitively than other liver function tests. Significance of AKBR for monitoring the graft function in postoperative management after liver transplantation is discussed.

3-Hydroxybutyric Acid↗

Protective effect of platelet-activating factor antagonist on hepatic energy metabolism following transient hepatic inflow occlusion in rabbits.

To investigate whether or not platelet-activating factor (PAF) is a mediator of the liver injury resulting from transient hepatic inflow occlusion (Pringle's maneuver), the effect of pretreatment with a potent PAF antagonist (CV6209) on hepatic energy metabolism was evaluated following 30 min of inflow occlusion in rabbits. At 60 min after declamping, the arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox state (NAD+/NADH), increased to 1.10 +/- 0.05 (mean +/- SEM) in the CV6209 (5 mg/kg)-pretreated group (group 1, n = 5) compared with 0.72 +/- 0.06 (P less than 0.01) in the untreated group (group 2, n = 5). Hepatic energy charge at 60 min after declamping was significantly higher in group 1 than in group 2 (0.871 +/- 0.010 vs. 0.800 +/- 0.023; P less than 0.05). Pretreatment with CV6209 had no significant influence on these parameters in sham-operated animals. The present study demonstrates that pretreatment with CV6209 has a protective effect against the impairment of hepatic energy metabolism following transient hepatic inflow occlusion.

Animals↗

Arterial ketone body ratio during and after cardiopulmonary bypass.

This study is the first to investigate the alteration in hepatic function during and after cardiopulmonary bypass in 30 patients by measuring the arterial ketone body ratio, an index of mitochondrial redox potential (oxidized nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide). Although the preoperative arterial ketone body ratio was within normal limits (1.24 +/- 0.63), it decreased markedly 5 minutes after the start of cardiopulmonary bypass to 0.35 +/- 0.12 and remained at this low level throughout bypass. After bypass it continued to rise in a time-dependent fashion, returning to its preoperative level by the morning of the second postoperative day in normal convalescent patients. However, the ratio recovered more slowly in patients who required prolonged circulatory or respiratory support than in other patients. Thus we suggest that cardiopulmonary bypass had deleterious effects on the hepatic mitochondrial redox potential, which may contribute to homeostatic derangements and metabolic abnormalities.

Aged↗

Insulinopenia as a risk factor in hepatectomy and its resolution by intraportal insulin administration.

Insulopenia is a possible risk factor in hepatectomy, especially since insulin has been recognized to have a significant hepatotrophic effect. In the current study, insulinopenic patients were defined as those who showed abnormally low insulinogenic indexes (less than 0.6) on the oral glucose tolerance test, compared with those in 22 normal volunteers (1.16 +/- 0.57, mean +/- SD). The insulinogenic index represents the ratio of the cumulative enhancement of immunoreactive insulin (IRI) to the glucose level (delta IRI/delta glucose). Surgical outcomes were studied retrospectively in 17 insulinopenic patients who underwent hepatic resections from January 1987 to July 1988. Six of 10 patients in the major hepatic resection group showed postoperative complications, 5 of whom experienced hepatic failure resulting in hospital death. By contrast, all seven patients in the minor resection group tolerated the operations. From August 1988, intraportal insulin was prospectively administered as a posthepatectomy management technique to nine patients, eight of whom were diagnosed as insulinopenic. These patients all tolerated major hepatic resections including four hepatic vascular exclusion procedures with veno-venous bypass. In conclusion, the current study indicates that insulinopenic patients are high-risk candidates for major hepatic resection and that intraportal insulin administration has a beneficial effect on the postoperative management of these patients.

3-Hydroxybutyric Acid↗

Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period.

During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively.

Adult↗

Effect of glucagon on hepatic energy charge and arterial ketone body ratio in normal rabbits.

Glucagon has been regarded as a hepatotrophic factor, although it is also known to stimulate energy-consuming reactions in the liver, such as gluconeogenesis and ureogenesis. To clarify the effect of glucagon on the hepatic energy metabolism, the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state [( NAD+]/[NADH]), as well as those in energy charge and mitochondrial oxidative phosphorylation of the liver after IV glucagon injection were studied in normal rabbits. Arterial ketone body ratio decreased significantly from 1.04 +/- 0.08 to 0.61 +/- 0.11 (mean +/- SEM; P less than 0.01) within 30 minutes after glucagon injection. Hepatic energy charge also decreased from 0.883 +/- 0.014 to 0.789 +/- 0.014 (P less than 0.01) at 30 minutes, whereas mitochondrial phosphorylation rate inversely increased from 38.4 +/- 9.5 to 87.3 +/- 9.7 (nanomoles adenosine triphosphate per milligram mitochondrial protein per minute; P less than 0.01) at 30 minutes. Arterial ketone body ratio and energy charge were subsequently restored to the initial values at 60 minutes and 2 hours, respectively. The present study suggests that glucagon causes an increase in energy expenditure in the liver that results in a transient decrease in hepatic energy charge accompanied by a decrease in arterial ketone body ratio.

Adenine Nucleotides↗

Seventy-two-hour preservation of porcine liver by continuous hypothermic perfusion with UW solution in comparison with simple cold storage.

Porcine livers preserved for 72 hr using continuous hypothermic perfusion (CHP) were studied in order to compare the effects of CHP on energy metabolism with those of simple cold storage (SCS). The livers of the CHP group were perfused in situ for 72 hr at 7 degrees C with University of Wisconsin (UW) solution and FC-43 as an oxygen carrier, while those of the S1 group were stored ex situ for 48 hr at 4 degrees C in UW solution, and those of the S2 group for 72 hr. They were then recirculated with human blood at 37 degrees C for 2 hr for the evaluation of their viability. At the end of preservation, significantly higher levels of total adenine nucleotides (TAN) and energy charge (EC) were observed in the CHP group compared with the S1 and S2 groups. At 2 hr recirculation, the level of TAN was significantly higher in the CHP group than in the S1 and S2 groups. The EC level was also higher in the CHP group than in the S2 group. During recirculation, the ketone body ratio (acetoacetate/beta-hydroxybutyrate) was higher in the CHP group than in the S2 group. The values in the CHP group were above 1.0 after 45 min recirculation. There were no significant differences in the pyruvate/lactate ratio and lactate level between the CHP and S1 groups. However, these values were significantly different from those in the S2 group. The present findings demonstrate that CHP using UW solution and the oxygen carrier was better able to preserve the energy metabolism of the porcine liver for 72 hr than 48-hr SCS in UW solution.

Adenine Nucleotides↗