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Biomedical subjects

K Kumada

Publications and source records attributed to K Kumada.

At least 19 recordsLinked 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

Preserved mitochondrial function by allopurinol despite deteriorated hemodynamics in warm ischemia-damaged canine liver.

To investigate the pathophysiology of warm ischemia (WI) of the liver, the changes in hemodynamics and energy metabolism were studied during and after 60-min complete WI induced by total hepatic vascular exclusion (HVE) in the canine model. Hepatic arterial blood flow after WI was maintained at 76% of the pre-ischemic level, while portal blood flow was only 27% of the pre-ischemic level associated with increased portal vein pressure, which was twice the pre-ischemic level, resulting in a decrease of total hepatic blood flow to 46% of the pre-ischemic level. Concentration of tissue lipid peroxide increased after WI. Arterial blood ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, could not recover to the pre-ischemic level after termination of WI. However, when 100 mg/kg of allopurinol (xanthine oxidase inhibitor) was administered intravenously 10 min prior to initiating WI, AKBR was restored to the pre-ischemic level at 30 min after WI in spite of the fact that allopurinol administration to one group produced no remarkable changes in the hepatic hemodynamics compared with the group without allopurinol treatment. Concentration of adenine nucleotides was significantly higher for the treated group at the end of and after WI than for the group without allopurinol treatment and was maintained at a higher level even after WI. Lipid peroxide production was suppressed. Electron microscopic examination revealed that allopurinol treatment could not prevent mitochondrial swelling. It is suggested that WI causes injury primarily to the portal sinusoidal circulation, resulting in portal congestion concomitant with high portal pressure after the release of WI. Allopurinol could prevent the deterioration of mitochondrial ATP metabolism, and was able to inhibit lipid peroxide production, resulting in the rapid recovery of mitochondrial redox state in spite of the fact that it produced no amelioration of hepatic hemodynamics and morphological alterations.

Adenosine Triphosphate

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

Maintenance of liver graft viability in the state of brain death. Synergistic effects of vasopressin and epinephrine on hepatic energy metabolism in brain-dead dogs.

The influence of vasopressin and epinephrine on hepatic energy metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) and hepatic energy charge (EC) in brain-dead dogs. Mean arterial blood pressure (MABP) was significantly decreased from 125.5 +/- 5.5 to 53.4 +/- 1.7 mmHg after complete brain death (P less than 0.01). In the control group AKBR and EC were maintained at near the normal values thereafter, despite marked hypotension. Combined administration of vasopressin and epinephrine sustained AKBR normally and improved MABP above 90 mmHg (P less than 0.01). EC was also maintained within the normal range at 5 hr after initiation of administration of the drugs. By contrast, vasopressin or epinephrine alone maintained AKBR and EC at near the normal values, but improved MABP just slightly to around 60 mmHg (P less than 0.01). As for the volume control, the urinary output was significantly smaller in the vasopressin and epinephrine-treated group than in the control group (P less than 0.05). It is suggested that combined administration of vasopressin and epinephrine has a synergistic effect in improving the hemodynamics and maintenance of the energy status of the liver. This regimen is recommended as a good one for maintaining potential liver donors in the state of brain death.

Adenine Nucleotides

The introduction of microvascular surgery to hepatic artery reconstruction in living-donor liver transplantation--its surgical advantages compared with conventional procedures.

Microvascular surgery for the reconstruction of the graft artery has been used since the 8th case in our series of 14 liver transplantations using living-related donors, and the clinical results have been compared between the first seven cases (the Loupe group) and the last seven cases (the Micro group). Seven arteries in 7 grafts were reconstructed with the use of loupe magnification in the Loupe group, while 8 arteries in 7 grafts were anastomosed with microscopic techniques in the Micro group. Statistically, there was no difference between the two groups in general background, including age, body weight and primary disease of the recipient, and in medical and surgical factors possibly relating to postoperative thrombosis of the hepatic artery. In two cases in the Loupe group, one or two additional reconstructions were necessary to obtain sufficient blood flow, while 8 arteries were anastomosed in the Micro group without any arterial complication in the postoperative period. There was no difference in time required for completing the arterial reconstruction (45.1 +/- 18.1 min in the Loupe versus 44.4 +/- 6.9 min in the Micro [mean +/- SEM]). Postoperative ultrasonic Doppler duplex study demonstrated a temporary decrease in the arterial flow in 2 cases of the Loupe group, and partial thrombosis of the artery was suspected. Additionally there were two episodes of hepatic artery thrombosis in 1 case of the Loupe group, in which emergent revision for thrombectomy and reanastomosis was performed at the first episode. This illustrated the higher incidence of arterial complications in the Loupe group compared with the Micro group (4 episodes/7 arteries in the Loupe versus 0/8 arteries in the Micro, P less than 0.05). In the present series there were no graft failures or arterial complications in the three deaths in the series. The clinical improvements achieved by microvascular surgery in living-donor liver transplantation suggest an alternative technical strategy for dealing with problematic arterial reconstruction in adult liver transplantation.

Child

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

[A case of HBsAg positive liver cirrhosis who died after withdrawal of steroid].

A 42-year-old male was admitted with subarachnoidal hemorrhage. Dexamethasone 224 mg was used to reduce brain edema. His operation was successful without blood transfusion. No remarkable signs and symptoms were found except HBsAg positive and mild GPT elevation during his admission. He was discharged on the 33rd day. But 2 weeks later, he felt general fatigue and became worse day by day. He was re-admitted on the 75th day. Several therapies were given but he died of hepatic failure on the 85th day. The autopsy showed liver cirrhosis with massive necrosis. We believed that the steroid-withdrawal-phenomenon caused excessive immunological response and this process caused his hepatic failure leading to death.

Adult

Tolerance of the liver as measured by ketone body ratio and hepatocyte energy charge to 120 minutes acute venous congestion in dogs.

Although acute passive hepatic congestion (APHC) sometimes occurs in patients undergoing open heart surgery or liver transplantation, the effects and safety limits of APHC on hepatic energy status have yet to be investigated. The present study reports an APHC model in 11 dogs in comparison with a control in 9 dogs by clamping the throacic inferior vena cava with passive venovenous shunt (APHC group) and by clamping the same with an active shunt at a rate of 60 ml/min/kg (control group). We investigated the effects of 120-min APHC on hepatic energy status by assessing the changes in arterial ketone body ratio (KBR) and hepatic energy charge (EC). After induction of the APHC, portal vein pressure elevated significantly to almost three times the control level. KBR decreased significantly for 60 min as compared with that of the control, but gradually recovered thereafter, returning to the preclamping level after reversal. Although total hepatic blood flow after 60-min clamping was approximately 18% of the preclamping value, no significant differences in EC and KBR values were seen after 60-min clamping as compared with preclamping and the control. All dogs in both groups survived at least 1 week. In this experimental model, 120-min APHC had no long-term effects on hemodynamics and energy production in the liver.

Acute Disease

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

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

Hepatic energy status in hypotension of different aetiologies in dogs.

1. The alterations in hepatic energy metabolism in hypotension induced by the administration of trimetaphan camsylate (Arfonad) were investigated in comparison with those produced by hypotension resulting from massive haemorrhage by measuring the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, and other indices of hepatic energy metabolism together with simultaneous measurement of hepatic blood flow in dogs. 2. Mean arterial blood pressure was decreased from 130 mmHg to 60 mmHg by the continuous intravenous infusion of trimetaphan camsylate or by the use of Wiggers' shock model. In hypotension induced by trimetaphan camsylate, the arterial ketone body ratio, ATP and total adenine nucleotide concentrations and energy charge were maintained at near-control values throughout the experimental period. By contrast, the arterial ketone body ratio decreased from 1.04 +/- 0.09 to 0.29 +/- 0.06 at 3 h after haemorrhage in Wiggers' shock model (P less than 0.01). The ATP and total adenine nucleotide concentrations and energy charge also decreased significantly in this model (P less than 0.05). The difference in hepatic energy status was also shown by data from 31P nuclear magnetic resonance spectroscopy. 3. During hypotension, portal venous and total hepatic blood flows diminished significantly compared with the control values in each group (P less than 0.01). Although there was no significant difference in total hepatic flow between the two groups, the portal venous blood flow in hypotension induced by trimetaphan camsylate was significantly higher than that in Wiggers' shock model (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Temporary portal vein arterialization as an attractive option in canine orthotopic partial liver transplantation.

We performed 22 canine orthotopic partial liver transplantations (PLTs) with three different revascularization methods; portal vein arterialization (PVA group, n = 11), hepatic arterial shunt (HAS group, n = 5), and conventional portal vein reperfusion (control group, n = 6). Our purpose was to evaluate the feasibility of PVA as a revascularization technique in PLT assessing the changes in arterial ketone body ratio (KBR) as an index of hepatic energy status. After the first anastomosis (left hepatic vein), the ischemic partial liver graft was revascularized with arterial blood flow shunted from the external iliac artery to the hepatic side of the portal vein (PVA group) or the proper hepatic artery (HAS group). Both anhepatic period and ischemia time were significantly shortened in groups PVA and HAS as compared with those in control. In the PVA group, 10 out of 11 recipients survived for at least 5 days (14.2 +/- 3.8 days, mean +/- SEM), while 3 out of 5 (5.2 +/- 1.0) survived in the HAS group and 4 out of 6 (6.2 +/- 1.3) in the controls. Although portal blood flow during PVA was only about 25% of the total hepatic blood flow at preclamping, the KBR was rapidly restored after PVA and showed almost the same values at preclamping. The KBR values during the arterialization time and initial velocity of KBR recovery in the PVA group were significantly higher than those in the HAS and control groups. These results suggest that PVA presents an attractive option in PLT.

Animals