Takuya Inomoto

Experiences of 120 microsurgical reconstructions of hepatic artery in living related liver transplantation

BACKGROUND We reviewed 120 microsurgical reconstructions of a hepatic artery in living related liver transplantation and discussed the problems encountered. METHODS From January 1991 to July 1994 we performed a series of 105 living related liver transplantations on children with end-stage liver disease. Arterial reconstruction was performed under the optical field of a continuous zoom magnification of approximately 10 times with an operating microscope. RESULTS Twenty-six percent of the graft arteries were less than 2 mm in diameter. The time required for an arterial reconstruction was 49.5 +/- 1.8 minutes. In 15 of the 31 cases in which there were two graft arteries, two arterial reconstructions were required. The caliber differences between the graft artery and the recipient artery in 30 instances was dealt with by cutting an undersized artery obliquely (17 instances), by fish-mouth method (10 instances), by end-to-side anastomosis (1 instance), or by funnelization method (2 instances). In one case we performed an intimal dissection of a recipient hepatic artery and substituted a splenic artery. Consequently, hepatic arterial thrombosis occurred in only two cases (1.7%). CONCLUSIONS Microsurgical technique has overcome the high risk of hepatic arterial thrombosis in cases of fine graft arteries, enabled the reconstruction of arteries with caliber difference, and decreased arterial complications with its delicate manipulation.

LIVING RELATED LIVER TRANSPLANTATION ACROSS ABO BLOOD GROUPS

We performed 13 pediatric liver transplants from ABO-incompatible living related maternal or paternal donors using a combination of preoperative removal of isohemagglutinin and postoperative immunosuppressive therapy with FK506 and prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The data obtained indicated that the preoperative removal of isohemagglutinin prevented hyperacute humoral rejection with hemorrhagic infiltration in the sinusoids in 10 successful cases. The incidence of acute rejection was not significantly different among ABO-identical, -compatible, and -incompatible groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

Graft size‐matching in living related partial liver transplantation in relation to tissue oxygenation and metabolic capacity

The influence of graft size-matching on tissue oxygenation and metabolic capability was studied in living related partial liver transplantations for 47 pediatric patients. Their age ranged from 4 months to 17 years 3 months, their body weight from 4.0 to 58.0 kg, graft weight from 191 to 440 g, and graft weight/recipient body weight ratio from 0.61% to 6.0%. Tissue oxygenation and its heterogeneity were investigated by measuring oxygen saturation of hemoglobin in the liver sinusoid (SO2), coefficient of variation of SO2, and arterial ketone body ratio. The metabolic capacity of the graft was investigated by measuring bilirubin clearance, recovery of cholesterol esterification, and ketone body production. In infants with a relatively large liver graft, both intra- and extracellular oxygenation remained low soon after reperfusion but recovered to the control value by the end of the operation. In adolescent recipients of a relatively small graft, by contrast, synthetic and detoxification capacities were relatively deficient; however, these improved with time. These results indicate that sufficient tissue oxygenation and liver regeneration are essential for successful liver transplantation with relatively large and small grafts, respectively.

Changes in the distribution of the control of the mitochondrial oxidative phosphorylation in regenerating rabbit liver

Applying the metabolic control theory, inhibitor titration studies were carried out on Complex I, III, IV, ATP synthase, ATP/ADP carrier and P(i) carrier of mitochondrial oxidative phosphorylation in normal and regenerating rabbit liver in order to examine the acceleration mechanism of mitochondrial oxidative phosphorylation. In regenerating rabbit liver the rate of state 3 respiration, respiratory control ratio and phosphorylation rate in the presence of mM glutamate, 250 microM ADP and 3 mM inorganic phosphate increased significantly as compared with the control by 73%, 48% and 76%, respectively. The control of the rate of state 3 respiration in normal liver was exerted by Complexes I, IV and steps other than the aforementioned six steps, whose flux control coefficients were 0.317, 0.214 and 0.469, respectively. By contrast, in regenerating liver, the control was more evenly distributed among these steps in oxidative phosphorylation and the possibility is suggested that Complexes I, IV and steps other than the six steps are activated during regeneration. The activation of Complexes I and IV was attributed to their increased activity, since it was not accompanied by an increase in the amount of the enzymes.

Intraoperative measurement of the graft oxygenation state in living related liver transplantation by near infrared spectroscopy

Abstract Graft oxygenation plays an important role in successful liver transplantation. Intraoperative changes in the oxygenation state of the liver graft were measured by near infrared spectroscopy in 28 cases of living related liver transplantation. Oxygen saturation of hemoglobin in the liver (hepatic SO2) changed from 81.2%± 1.5% (mean ± SEM) before donation (in the donor) to 49.7%± 4.2% after portal reflow, to 58.4%± 5.0% after arterial reflow, and then to 71.4%± 3.9% before closure. Mean hepatic SO2 was positively correlated with portal flow rate as measured by duplex Doppler sonography. Cases with low portal flow rate showed a high coefficient of variation (SD/mean) of hepatic SO2, indicating heterogeneous tissue oxygenation. Though graft size was expected to affect the graft oxygenation state, hepatic SO2 was fairly independent of the graft‐to‐recipient weight ratio. In two cases with markedly low hepatic SO2, postoperative graft dysfunction occurred. This study suggest that the method of near infrared spectroscopy is reliable and useful for assessing the graft oxygenation state in liver transplantation.

Quantitative analysis of redox gradient within the rat liver acini by fluorescence images: effects of glucagon perfusion

The redox gradient along the sinusoid in the rat liver was studied using a redox scanner, a device based on tissue fluorescence scanning spectroscopy measuring the fluorescence signals of oxidized flavoprotein (FP) and reduced pyridine nucleotide (PN). The FP/(FP+PN) ratio reflects the mitochondrial redox state in the liver tissue. The distribution of mitochondrial redox state on the scanned area is expressed as two-dimensional gray-scale images with a 20 micron resolution. Using this instrument, we have scanned a 2.5 x 2.5 mm area of the frozen rat liver sample to investigate the redox gradient within acini and the effects of glucagon on the changes in the redox distribution. The redox images obtained in the perfused livers showed mosaic patterns implicating a regular heterogeneity of redox state in an acinus. The analysis of gradient curve, furthermore, clarified that the redox level in an acinus decreased sigmoidally from the periportal to the pericentral region. Glucagon, which has been reported to reduce the intracellular redox state, decreased the redox potential in whole acini, especially, in the periportal region, when compared with the perfusion without glucagon. These results strongly indicate an intraacinus heterogeneity of glucagon function, with glucagon selectively operating in the upstream of the sinusoid.

Pneumoperitoneum following the spontaneous rupture of a gas-containing pyogenic liver abscess: report of a case.

Abstract We report herein the case of a ruptured liver abscess that resulted in pneumoperitoneum. A patient with diabetes mellitus presented with symptoms of acute abdomen. The plain abdominal radiograph and computed tomography findings revealed abdominal free air and a gas-containing liver abscess, whereby a diagnosis of a ruptured liver abscess was made. An emergency operation was performed, and the abscess was drained followed by peritoneal lavage and the administration of appropriate antibiotics. To the best of our knowledge, very few cases of spontaneous pneumoperitoneum occurring secondary to the rupture of a gas-containing liver abscess have been encountered in Japan.

Delayed oxidation of intramitochondrial pyridine nucleotide oxidoreduction state as compared with tissue oxygenation in human liver transplantation

Intra- and post-operative oxygenation of graft liver and subsequent oxidation of the intramitochondrial oxido-reduction state of pyridine nucleotide were studied in partial liver transplantation from living related donors with the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood (AKBR), the ratio of oxidized flavoprotein to reduced pyridine nucleotide (FP/PN ratio) and oxygen saturation of hemoglobin in liver tissue (hepatic SO2). Decreased hepatic SO2 and its heterogenous distribution after reflow of portal vein and hepatic artery were normalized by the end of operation, while the intramitochondrial oxido-reduction state was still reduced at the end of operation and was normalized only at 24 h after the operation. The observed delay in oxidation of the intramitochondrial oxido-reduction state as compared with tissue oxygenation indicates the transition of the intramitochondrial oxido-reduction state associated with the initiation of metabolic activity from the cold preserved state, and suggests an important role for microcirculation in the normalization of the oxido-reduction state.

Preoperative assessment of hepatic function: Utility of a new convenient two-compartment model analysis using galactosyl human serum albumin scintigraphy.

Background and Aim: Preoperative hepatic function was evaluated using technetium‐99 m‐diethylenetriaminepenta‐acetic acid‐galactosyl‐human serum albumin (Tc‐GSA) and a scintillation camera to detect hepatic Tc‐GSA uptake by the asialoglycoprotein receptor.

CHANGES IN GLUCOSE TRANSPORTER 2 AND CARBOHYDRATE-METABOLIZING ENZYMES IN THE LIVER DURING COLD PRESERVATION AND WARM ISCHEMIA: The Possibility of Evaluating the Viability of the Liver Graft before Transplantation

In order to examine glucose metabolism in liver grafts during cold preservation (24 and 48 hr), warm ischemia (60 and 120 min), a combination of the two and reperfusion, the amount of protein and mRNA of glucose transporter 2 and the activities of enzymes in glycolysis (glucokinase, phosphofructokinase, pyruvatekinase), gluconeogenesis (glucose 6-phosphatase, fructose 1,6-bisphosphatase), and the pentose phosphate pathway (glucose 6-phosphate dehydrogenase) were measured. It appeared that glucose transport, the pentose phosphate pathway, and gluconeogenesis were maintained during cold preservation and warm ischemia. The activity of glucokinase significantly decreased from the control value of 1.33 +/- 0.23 IU/g protein to 0.70 +/- 0.17 (24 hr, P<0.05) and 0.57 +/- 0.12 (48 hr, P<0.01) only during cold preservation. However, the activity of phosphofructokinase significantly decreased from the control value of 4.37 +/- 0.06 IU/g protein to 2.67 +/- 0.15 (60 min, P<0.0001) and 1.53 +/- 0.06 (120 min, P<0.0001) only during warm ischemia. This indicates that glycolysis deteriorates during both cold preservation and warm ischemia and demonstrates further that the balance between glycolysis and gluconeogenesis shifts to gluconeogenesis. Even when cold preservation was combined with warm ischemia, the activity of glucokinase decreased only during cold preservation and the activity of phosphofructokinase decreased only during warm ischemia. Furthermore, these changes were time-dependent. It is suggested that they can be used as a clock to measure the durations of cold preservation and warm ischemia separately and that the magnitude of an ischemic injury to a liver and a liver grafts viability can be indirectly estimated before transplantation.