Wataru Kamiike

Adenine nucleotide metabolism and its relation to organ viability in human liver transplantation

The relationship between adenine nucleotide metabolism and ischemic damage was studied in human liver. Thirty transplanted grafts were divided into two groups assording to their functional outcome. Cellular adenine nucleotide levels were assayed by high-performance liquid chromatography. During cold ischema, the adenosine triphosphate (ATP) level was not correlated with graft function, but two grafts with low total adenine nucleotides (TAN) levels showed poor function after transplantation. After recirculation, the ATP level showed good recovery in grafts that functioned satisfactorily (n=24), 5.47±1.51 mUmol/g dry weight), but remained low in poorly functioning grafts (n=6), 3.30pL 1.68 mUmol/g dry weight) (P<0.01). Bile production, used as a parameter of initial function, was observed shortly after implantation in 17 of 24 grafts that functioned satisfactorily, but in only 1 of 6 poorly functioning grafts. It is concluded that loss of ademine nucleotides and lack of bile production during transplantation are good markers of damaged grafts in human liver transplantation.

Correlation between cellular ATP level and bile excretion in the rat liver

The influence of the cellular level of adenosine triphosphate (ATP) in the liver on bile excretion was studied in rats. In ischemia, the cellular ATP level decreased rapidly--and, concomitantly, bile flow stopped within 5 min. Administration of L-ethionine i.p. to rats reduced the bile flow rate with decrease in the cellular ATP level. The correlation between the bile flow rate and the cellular ATP level was confirmed in a liver perfusion system. On anoxic perfusion, the ATP level and bile flow rate changed in the same manner as in ischemia. The recovery rates of both on reoxygenation decreased with increase in the anoxic perfusion period. During perfusion under oxygenated conditions, decrease in cellular ATP to various levels by infusion of various concentrations of potassium cyanide, an inhibitor of respiration, resulted in corresponding and concomitant suppression of bile excretion. Kinetic analysis of the bile flow rate revealed a Michaelis-Menten-type curve for the cellular ATP level. The apparent Kms for ATP of bile flow rate in L-ethionine-treated rat liver and liver perfused with potassium cyanide were 1.0 and 1.6 mM, and their Vmax values were 4.1 and 2.5 microliter/min/g liver, respectively. The concentrations of main bile components, such as phospholipids, cholesterol, and taurocholate increased, but their total outputs decreased with decrease in the ATP level, and returned to the normal range with recovery of the ATP level. Thus, it was shown experimentally that the extent of hepatic injury can be assessed simply by monitoring the bile flow rate, which reflects the cellular level of ATP.

Preservation of recurrent laryngeal nerve invaded by differentiated thyroid cancer.

OBJECTIVE This study was undertaken to determine whether the recurrent laryngeal nerve involved in differentiated thyroid carcinoma could be preserved. SUMMARY BACKGROUND DATA Few investigations have provided definitive results concerning preservation of the recurrent laryngeal nerve involved in thyroid cancer. Complete excision with resection of the recurrent laryngeal nerve reportedly did not improve survival over incomplete excision in differentiated thyroid carcinoma. METHODS A retrospective study was performed with the medical records of 50 patients with differentiated carcinoma and preoperative normal vocal cord function to investigate outcomes of recurrent laryngeal nerve preservation including local recurrence, prognosis, and postoperative vocal cord function. The recurrent laryngeal nerves on 1 or both sides were preserved in 23 patients (the preserved group), whereas the involved recurrent laryngeal nerve of the other 27 patients was resected (the resected group). RESULTS Backgrounds of patients were similar between the resected and preserved groups. The number of patients with recurrences in each group was similar, and incidence of local, regional, and distant metastatic recurrences were not different between the groups. Postoperative overall survival of the preserved group was similar to that of the resected group (p = 0.1208). More than 60% of patients or of nerve at risk in the preserved group restored normal vocal cord function within 6 months. Some functional vocal cord movement was recognized in 80% of patients or of nerve at risk. All patients in the resected group including patients with nerve anastomosis showed permanent paralysis of the ipsilateral vocal cord. CONCLUSIONS These results suggested that the recurrent laryngeal nerve, even if infiltrated by differentiated thyroid cancer, is worthwhile to preserve for maintenance of postoperative vocal cord function without affecting the incidence of local recurrence or prognosis.

Laparoscopic intragastric surgery for gastric leiomyoma

Abstract. Laparoscopic intragastric surgery (LIGS) was performed on a 63-year-old man with a gastric leiomyoma adjacent to the cardia. Because the tumor was about 5 cm in maximum diameter and showed ulceration, the possibility that the tumor was a leiomyosarcoma could not be ruled out preoperatively. Conventionally, major surgery has been performed on patients with a tumor located near the cardia, although it was not always malignant. Enucleation by LIGS enabled us to avoid excessive invasiveness and provided a favorable result. LIGS may be an appropriate new, minimally-invasive operation for gastric myogenic tumors and should be considered for such cases.

ATTENUATION OF WARM ISCHEMIC INJURY OF RAT LUNG BY INFLATION WITH ROOM AIR-ASSESSMENT OF CELLULAR COMPONENTS AND THE SURFACTANT IN THE BRONCHOALVEOLAR LAVAGE FLUID IN RELATION TO CHANGES IN CELLULAR ADENOSINE TRIPHOSPHATE

Studies were made on the effects in rat lungs of aerobic and anaerobic conditions on the intracellular levels of adenosine triphosphate and its related metabolites, the releases of intracellular enzymes, and the secretion of pulmonary surfactant. After warm ischemia for 120 min, the ATP content of lungs inflated with air was significantly higher (8.0±1.2 μmol/g dry weight) than those of deflated lungs and lungs inflated with nitrogen (0.8±0.7 μmol/g dry weight and 2.0±0.7 μmol/g dry weight, respectively; P<0.001). The amounts of intracellular enzymes, such as lactate dehydrogenase, cyto-solic and mitochondrial aspartate aminotransferase, and protein in the bronchoalveolar lavage fluid (BALF) of air-inflated lungs were significantly less than those in BALFs of deflated and nitrogen-inflated lungs (P<0.001). The BALF-contents of dipalmitoyl phosphatidylcholine (DPPC), the main component of alveolar surfactant of aerobic and anaerobic ischemic lung were, however, similar. During 120-min warm ischemia after lavage, air-inflated lungs secreted significantly more DPPC into the alveolar space than nitrogen-inflated lungs did (P<0.001). We conclude that cell membranes in the lungs are damaged under anaerobic conditions, but that inflation of ischemic lungs with air is effective for protecting them from cell injury and for maintaining the intracellular level of ATP and the ability of the cells to secrete pulmonary surfactant.

Splenic artery embolization using contour emboli before laparoscopic or laparoscopically assisted splenectomy.

The present study assessed preoperative splenic artery embolization using spherical embolic material, super absorbent polymer microspheres (SAP-MS), before laparoscopic or laparoscopically assisted splenectomy. Distal splenic artery embolization using 250 to 400 &mgr;m SAP-MS was performed in nine cases with ITP and in seven cases with the other diseases with splenomegaly. Laparoscopic or laparoscopically assisted splenectomies, including a hand-assisted procedure and the procedure involving left upper minilaparotomy, were done 2 to 4 hours after embolization. Conversion to traditional laparotomy was not required in any of the 16 cases, while conversion to 12-cm laparotomy was required in one case with massive splenomegaly. Mean operating time was 161 minutes, and mean intraoperative blood loss was 290 mL. No major postoperative complications were identified, and only one patient reported postembolic pain before surgery. Preoperative splenic artery embolization using painless embolic material, SAP-MS, would be effective for easy and safe laparoscopic or laparoscopically assisted splenectomy.

Laparoscopic cholecystectomy and time-course changes in renal function: The effect of the retraction method on renal function

AbstractBackground: Recently, the retraction method has been used to reduce intraabdominal pressure (IAP) during laparoscopic surgery. The purpose of this study was to determine the serial changes in renal function during laparoscopic cholecystectomy (LC) using the retraction method. Methods: Urine output, effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) were measured serially in seven patients who underwent LC with 12 mmHg pneumoperitoneum (High-IAP group) and five who underwent LC using the retraction method with 4 mmHg pneumoperitoneum (Low-IAP group). Results: Urine output, ERPF, and GFR were decreased during pneumoperitoneum in the High-IAP group, whereas no significant changes in any of these parameters were observed in the Low-IAP group. Conclusions: Our findings demonstrate that reduction of IAP to 4 mmHg using the retraction method prevents the transient renal dysfunction caused by prolonged 12 mmHg pneumoperitoneum during LC, suggesting that the retraction method reduces the risk of perioperative renal dysfunction during laparoscopic surgery.

Levels of purine compounds in a perfusate as a biochemical marker of ischemic injury of cold-preserved liver.

Biochemical markers of ischemic injury of rat liver were studied in an extracorporeal perfusion system. During anoxic perfusion, purine compounds appeared in the perfusate as soon as they were formed in the liver and their recovery in the perfusate balanced the loss of adenine nucleotides from the liver. In contrast, cytosolic aspartate aminotransferase did not appear in the perfusate at slow rates of liver perfusion or during hypothermic perfusion. The production of purine compounds was further investigated in hypothermically preserved liver in connection with the restoration of some metabolic functions of liver. The amount of purine compounds released into the perfusate was found to be closely related to the degrees of damage of the hepatic functions of gluconeogenesis, ureogenesis, and mitochondrial respiration on reperfusion. These results indicate that release of purine compounds into the perfusate is a good marker of ischemic damage.

Regulation of complement-mediated swine endothelial cell lysis by a surface-bound form of human C4b binding protein.

BACKGROUND Human C4b-binding protein (C4bp) functions as a cofactor for factor I in the degradation of C4b and C3b and, in addition, accelerates the rate of decay of the C4b2a complex. METHODS In this study, we constructed a surface-bound form of human C4b-binding protein (C4bp-PI) consisting of a short consensus repeat 1-8 of the alpha-chain of C4bp and a glycosyl phosphatidylinositol (GPI) of the decay-accelerating factor (CD55) and established stable swine endothelial cell (SEC) lines expressing C4bp-PI by transfection of cDNA. Amelioration of complement-mediated lysis by the transfectant molecules was tested as an in vitro hyperacute rejection model of swine to human discordant xenograft, using the lactate dehydrogenase assay. RESULTS Flow cytometric profiles of the stable SEC lines with C4bp-PI showed a high level of expression of this molecule. The cell lysate of the SEC line with C4bp-PI showed strong cofactor activity in not only C4b but also C3b, whereas the activity of plasma C4bp to bind to C3 was very weak. Approximately 150 x 10(4) molecules of C4bp-PI per SEC blocked human complement-mediated cell lysis by approximately 75%. CONCLUSIONS The results suggest that the surface-bound form of C4bp will be very useful in clinical xenotransplantation.

Generation of nitric oxide as a rejection marker in rat pancreas transplantation.

In clinical pancreas transplantation, no reliable marker for the early diagnosis of acute rejection has been reported. This is one reason why the graft survival rate of pancreas transplantation alone is much lower than that of other organs, such as hearts, livers, and kidneys. We designed an experiment to investigate acute rejection of pancreas allografts in hyperglycemic rats by measurement of blood glucose levels and nitric oxide (NO) products (nitrite plus nitrate, and nitrosyl hemoglobin). As recipients, Lewis rats were rendered hyperglycemic by intravenous injection of streptozotocin before transplantation. F344 rats were used as donors of pancreas allografts. Lewis rats were also used as donors of syngeneic pancreas grafts. After transplantation, the blood glucose level returned to a normal level and rejection was defined as the recurrence of hyperglycemia. The mean survival time of pancreas allografts was 14 +/- 0.7 days. The plasma level of nitrite plus nitrate in allografted rats peaked on postoperative day 7. Electron spin resonance spectra of NO bound to hemoglobin were detected in the blood from allografted rats with a peak on postoperative day 7, whereas NO bound to hemoglobin was not detected in the blood from recipients of syngeneic grafts at any sampling time. The results show that NO was synthesized in the earlier period than the elevation of the blood glucose level during rejection after pancreas transplantation in rats.