Biomedical subjects

Y Ku

Publications and source records attributed to Y Ku.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Experimental study on TNF-alpha linked percutaneous isolated hepatic chemoperfusion (PIHP)].

Recently, isolated hepatic perfusion (IHP) with high-dose TNF-alpha for hepatic malignancies has again attracted attention as a locoregional chemotherapy. A novel system of hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) is a minimal invasive surgery for high-dose chemotherapy of the liver. This study was undertaken to determine whether this novel system could limit systemic exposure to TNF-alpha following hepatic arterial infusion (HAI) when combined with anti TNF-alpha antibody. Beagles were allocated into two groups; group I (n = 4), TNF-alpha + anti TNF-alpha antibody and group II (n = 5), TNF-alpha only (control). All animals received HAI of 50 micrograms/kg of recombinant human TNF-alpha over 20 min with complete hepatic venous isolation. In group I, 250 micrograms/kg of antibody was administered into the hepatic venous outflow line over 30 min after the initiation of HAI. The Cmax (ng/ml) of systemic TNF level was significantly lower in group I (125 +/- 57) than in group II (825 +/- 283) (p < 0.05). The AUC (mg.min/ml) of the systemic TNF level was significantly lower in group I (2.0 +/- 1.0) than in group II (34.5 +/- 9.5) (p < 0.01). By use of anti TNF antibody, systemic exposure to TNF was reduced efficiently. These results indicated that HVI.CHP may be applicable to the TNF-alpha linked chemoperfusion to the liver in combination with anti TNF-alpha antibody.

Animals↗

PubMed1998

[Pharmacokinetic comparison between cisplatin and nedaplatin in hepatic arterial chemotherapy using complete hepatic venous isolation and charcoal hemoperfusion].

We undertook a pharmacokinetic comparison between cisplatin and nedaplatin in hepatic arterial chemotherapy using complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs received a 20-min hepatic arterial infusion of either 4 mg/kg cisplatin (Group I, n = 5) or 4 mg/kg nedaplatin (Group II, n = 5) under HVI.CHP. The CHP filter adsorption ratios did not differ significantly between the two groups. Drug clearance fractions by HVI.CHP in group II (free pt 45.9%, total pt 55.1%) were significantly higher than those in group I (free pt 23.4%, total pt 27.5%) (p < 0.05). In contrast, hepatic extraction ratios in group I tended to be higher than those in group II. These results indicated that extrahepatic distribution of cisplatin became lower than that of nedaplatin, when given via the hepatic artery, and that the pharmacokinetic advantage of HVI.CHP would be greater when a drug like nedaplatin with a relatively low hepatic extraction ratio is used. Thus, we concluded that nedaplatin is a more suitable drug than cisplatin.

Animals↗

PubMed1997

Protection of canine pancreatic microvascular endothelium against cold ischemic injury during preservation by the two-layer method.

BACKGROUND: Ischemic injury of the microvascular endothelium during cold preservation causes a disturbance of vascular microcirculation after reperfusion and results in graft failure. Recently we have shown that oxygenation of the canine pancreas during preservation by the two-layer method extends the period of preserved pancreatic viability. The aim of this study was to clarify the role of the oxygenation of the pancreas graft by the two-layer method in the viability of the microvascular endothelium during preservation. METHODS: After preservation of the canine pancreas by simple cold storage in Euro-Collins solution (EC) (group 1) or by the two-layer method using EC (group 2) for 48 hr, the viability of vascular endothelial cells was judged from nuclear trypan blue uptake. Pancreatic tissue perfusions were measured with a hydrogen gas clearance technique, and graft survival rates were examined after autotransplantation. In the control group, the grafts were autotransplanted without preservation (group 3). RESULTS: Graft survival rates were 0 of 5 (0%), 5 of 5 (100%), and 5 of 5 (100%) in groups 1, 2, and 3, respectively. The percentage of trypan blue-positive vascular endothelium in group 1 was significantly higher compared with group 3 (control) (26.4+/-1.7 vs. 7.4+/-4.3%, P<0.01). The two-layer method (group 2) decreased trypan blue uptake (11.3+/-3.7 vs. 26.4+/-1.7%, P<0.01). Pancreatic tissue perfusions after 2 hr of reperfusion were in inverse proportion to trypan blue uptake. Namely, pancreatic tissue perfusions in group 1 were significantly lower than group 3 (control) (45.6+/-12.8 vs. 64.5+/-20.6 ml/min/100 g, P<0.01). The two-layer method (group 2) improved pancreatic tissue perfusions (68.8+/-8.6 vs. 45.6+/-12.8 ml/min/100 g, P<0.01). CONCLUSION: We conclude that oxygenation of the pancreas during preservation by the two-layer method protects the microvascular endothelium from cold ischemic injury. Consequently, pancreatic microcirculation can be maintained after reperfusion, thus extending the period of preserved pancreatic viability.

Animals↗

PubMed1997

Peripancreatic fluid cytology: detection of early rejection versus graft pancreatitis after canine pancreatic transplantation.

It is particularly difficult to distinguish between early rejection and graft pancreatitis when early rejection produces an elevated serum amylase level. In this study we determined whether peripancreatic fluid cytology (PFC) can differentiate early acute rejection and graft pancreatitis as an alternative diagnostic tool to graft biopsy that has the potential of pancreatic fistula and hemorrhage. Sixty-two dogs received either a segmental pancreas allograft (n = 25) or autograft (n = 37) heterotopically in the neck. This study included five groups: allografts without immunosuppression (group A, n = 12), allografts with immunosuppression (group B, n = 13), autografts without immunosuppression (group C, n = 11), autografts with immunosuppression (group D, n = 12), and autografts treated by 45 minutes of pretransplant warm ischemia to induce acute graft pancreatitis (group E, n = 14). A closed suction drainage catheter was placed next to the graft to collect peripancreatic fluid daily after the transplant. PFC was performed using May-Gruenwald-Giemsa double-staining technique and compared to the corresponding histology through the observation period. In analyses of 50 functioning grafts, PFC performed on day 1 showed similar neutrophil accumulations in all groups. In sharp contrast, on days 3 and 6, group A had dramatically increased mononuclear cell concentrations in PFC, whereas groups B, C, and D showed significantly lower concentrations, the percent of mononuclear cells among total leukocytes being 47.3 +/- 23.4%, 11.8 +/- 4.9%, 4.3 +/- 1.8%, and 6.4 +/- 2.4% (day 3); and 32.7 +/- 9.8%, 10.5 +/- 4.8%, 7.2 +/- 4.2%, and 8.6 +/- 6.4% (day 6) in groups A, B, C, and D, respectively. On the other hand, in group E numerous degenerating neutrophils with a marked to moderate increase in necrotic tissue fragments were observed by PFC on days 3 and 6. In terms of graft histology on days 3 and 6, group A showed interstitial mononuclear cell infiltration indicating an acute rejection process, whereas groups B, C, and D had minimal inflammatory cell infiltration. In group E graft pancreatitis was histologically confirmed on days 3 and 6. These results suggest that PFC after pancreas transplantation could be a safe, simple, useful diagnostic tool for discriminating early graft rejection from graft pancreatitis.

Animals↗

PubMed1997

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Animals↗

PubMed1997

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Aged↗

PubMed1997

Recovery of pancreatic tissue perfusion and ATP tissue level after reperfusion in canine pancreas grafts preserved by the two-layer method.

We examined whether pancreas grafts preserved by the two-layer method maintained adenine nucleotides pool as substrates for ATP synthesis before reperfusion and had the ability to recover pancreatic tissue perfusion and synthesize ATP promptly after reperfusion. After preservation by the two-layer cold storage method using EC for 48 h (group 1) or simple cold storage in EC for 48 h (group 2), canine pancreas grafts were autotransplanted. In controls (group 3), canine pancreas grafts were autotransplanted without preservation. Tissue adenine nucleotide concentrations were measured using high-performance liquid chromatography, and pancreatic tissue perfusions were measured using the hydrogen gas clearance method. Graft survival rates were five of five, zero of five, and five of five in groups 1, 2, and 3, respectively. Total adenine nucleotide levels before reperfusion in group 1 were almost the same as in group 2. Furthermore, ATP tissue levels in group 1 before reperfusion were also the same as in group 2. However, tissue ATP levels in group 1 after 2 h of reperfusion (6.71 +/- 1.19 mumol/g dry weight) were significantly higher than group 2 (4.51 +/- 0.51 mumol/g dry weight; p < 0.05). On the other hand, pancreatic tissue perfusions in grafts preserved by the two-layer method (group 1) after 2 h of reperfusion were significantly higher than in group 2. We conclude that oxygenation of pancreas grafts during preservation by the two-layer method allows for ATP synthesis and leads to maintenance of the grafts' ability to recover ATP levels and tissue perfusions after reperfusion.

Adenine Nucleotides↗

PubMed1997

Pharmacological evaluation of portal venous isolation and charcoal haemoperfusion for high-dose intra-arterial chemotherapy of the pancreas.

BACKGROUND: A novel system of complete portal venous isolation and charcoal haemoperfusion (PVI-CHP) has been developed in an attempt to increase dose intensity while minimizing the systemic toxicity of the cytotoxic agent during intra-arterial chemotherapy of the pancreas. METHODS: Mongrel dogs were given doxorubicin (3 mg kg-1), infused over a 5-min period via the splenic artery, together with PVI-CHP (group 1; n = 5) or without PVI-CHP (group 2; n = 5). Plasma doxorubicin concentrations were determined in serial samples obtained from the inlet and outlet of the CHP filter and in samples obtained from the left jugular vein (systemic levels) for up to 30 min after initiation of drug infusion. Subsequently, specimens were obtained from the pancreas, liver and heart to determine tissue doxorubicin levels. RESULTS: The mean(s.d.) peak systemic concentration of doxorubicin in group 1 was 0.78(0.03) microgram ml-1, significantly lower than that in group 2 of 3.49(1.15) micrograms ml-1 (P < 0.01). The peak concentration of doxorubicin in group 1 was significantly lower (more than 90 per cent) than that before filtration (P < 0.01). Tissue doxorubicin concentration in the pancreas was similar in both groups. However, concentrations in the liver and heart were significantly lower in group 1 than in group 2 (P < 0.05). CONCLUSION: These results indicate that PVI-CHP can produce a significant reduction in systemic drug exposure and may allow dose intensification during intra-arterial chemotherapy for the pancreas.

Animals↗

PubMed1997

[A case of multiple colonic liver metastases treated successfully with percutaneous isolated liver chemoperfusion using cisplatin].

We herein report a case of multiple colonic liver metastases treated with repeated percutaneous isolated liver chemoperfusion of cisplatin under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) as an inductive treatment. The patient was a 70-year-old man who underwent curative resections for metachronous rectal and descending colonic cancer in 1979 and 1995, respectively. During outpatient follow-up, he showed increases of serum CEA level. An abdominal CT study demonstrated multiple low-density lesions in the bilateral lobes of the liver, indicating colonic liver metastases. The patient had a total of 2 treatments with percutaneous isolated liver chemoperfusion of cisplatin (total dose, 500 mg) under HVI.CHP. His post-treatment course was uneventful without side effects, including leukopenia and renal dysfunction. Serum CEA levels showed a sharp decrease to 160 ng/ml 3 months after treatment from the pretreatment value of 1,064 ng/ml. CT scan 3 months after treatment revealed remarkable tumor regression along with liquefaction of liver tumors, showing a partial response. These results suggested that repeated percutaneous isolated liver chemoperfusion of cisplatin under HVI.CHP is a potent inductive treatment for patients with multiple colonic liver metastases.

Aged↗

PubMed1997

[Efficacy of combined use of sodium thiosulfate in percutaneous isolated liver chemoperfusion of cisplatin under complete hepatic venous isolated and charcoal hemoperfusion].

We herein evaluated the efficacy of combined use of sodium thiosulfate (STS) in isolated liver chemoperfusion of cisplatin (CDDP) under complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 5), CDDP (4 mg/kg) + STS (4 g/body) and group II (n = 5), CDDP (4 mg/kg). In both groups, CDDP was intraarterially administered for 20 minutes under HVI.CHP. In addition, in group I, STS infusion was administered for 20 minutes via the outlet side of CHP filter. The adsorption rates of free and total CDDP of CHP filter were in a range of 50-80%, and the rates in group I were higher than in group II. At all sampling points, the AUC (microgram.min/ml) of free CDDP was not different between the two groups. However, the AUC of total CDDP at postfilter [group I: 35.3 +/- 2.7 (mean +/- SD); group II: 63.5 +/- 21.5] and systemic serum (group I: 24.9 +/- 8.6, group II: 43.5 +/- 13.5) was significantly lower in group I than in group II (p < 0.05). The cumulative amounts of urinary excretion of CDDP (microgram/kg) were 39.5 +/- 12.1 and 13.5 +/- 9.3 in groups I and II, respectively, showing a significant increase in group I (p < 0.01). These results indicated that the use of STS in percutaneous isolated liver chemoperfusion of CDDP under HVI.CHP could further reduce systemic toxicities of CDDP, by increasing CDDP filter extraction of CHP filter and urinary CDDP excretion.

Animals↗

PubMed1996

The effect of ouabain (inhibitor of an ATP-dependent Na+/K+ pump) on the pancreas graft during preservation by the two-layer method.

To clarify how synthesized ATP is utilized to maintain cellular integrity during preservation by the two-layer method, we examined the effect of ouabain, inhibitor of ATP dependent Na+/K+ pump, on ATP tissue levels, graft weight, and vascular endothelial cells during 48 hr preservation by the two-layer method and pancreatic tissue perfusion and graft survival after transplantation in a canine model. Ouabain treatment did not affect ATP production but prevented its utilization by the sodium pump, and actually significantly increased ATP levels and decreased the weight loss of the graft. In addition, ouabain caused a significant increase of nuclear trypan-blue staining in vascular endothelial cells and a significant decrease of pancreatic tissue perfusion at reperfusion. Consequently, the grafts did not survive. We conclude that the two-layer method allows sufficient synthesis of ATP to drive the sodium pump and maintains membrane integrity of parenchymal cells and vascular endothelial cells, thus extending the period of preserved pancreatic viability.

Adenosine Triphosphate↗

PubMed1996

Direct evidence of pancreatic tissue oxygenation during preservation by the two-layer method.

The purpose of this study was to measure directly tissue oxygen tension (PO2) of the ischemically damaged pancreas graft during preservation by the two-layer (University of Wisconsin solution/perfluoro-chemical) method at 20 degrees C using Clark-type polarographic oxygen electrodes and to make clear the relationship of tissue PO2 and ATP levels during preservation and graft survival after transplantation in a canine model. During warm ischemia, tissue PO2 and ATP were dramatically decreased. Tissue PO2 continued to decrease, and tissue ATP levels were not elevated during simple storage in oxygenated University of Wisconsin solution at 20 degrees C. On the contrary, during preservation by the two-layer method at 20 degrees C, tissue PO2 promptly increased and reached about 50% of the preprocurement level at 30 min of preservation. Then, tissue PO2 was maintained this level throughout the preservation period. Tissue ATP levels were still low in the first 1 hr, but after that tissue ATP increased in a time-dependent manner. Consequently, the two-layer method at 20 degrees C could restore the viability of pancreas damaged by warm ischemia during 3- and 5-hr preservation. We conclude that the ischemically damaged pancreas grafts were oxygenated, and tissue ATP was increased during preservation by the two-layer (University of Wisconsin solution/pefluorochemical) method at 20 degrees C. Consequently, the graft was resuscitated and survived after transplantation.

Adenosine↗

PubMed1996

Extending the margin of safety of preservation period for resuscitation of ischemically damaged pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C with thromboxane A2 synthesis inhibitor OKY046.

We have shown that 5-hr preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C allows ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. However, 8 hr of preservation using this method caused a disturbance of vascular microcirculation and did not resuscitate the grafts. The aim of this study was to examine the effect of thromboxane A2 synthesis inhibitor OKY046 on vascular endothelial cells and ATP tissue levels of canine pancreas during preservation using the two-layer (University of Wisconsin solution/perfluorochemical) method at 20 degrees C, and vascular microcirculation and pancreas viability after transplantation. Graft viability was judged by graft survival following autotransplantation. ATP tissue levels were measured by high-performance liquid chromatography at the end of preservation. Viability of the vascular endothelial cells was judged using nuclear trypan blue uptake of the graft after preservation. Pancreatic tissue perfusion was measured using an H2 clearance technique after reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5). However, 5-hr preservation made it possible to recover the pancreas (5/5); 8-hr preservation was not successful (0/3). ATP tissue levels after 5-hr and 8-hr preservation were 9.40+/-2.09 and 7.37+/-1.06 micromol/g dry weight, respectively, and OKY046 did not affect ATP synthesis during 8-hr preservation (8.44+/-0.92 micromol/g dry weight). The percentage of nuclear trypan blue uptake of endothelial cells in 8-hr-preserved grafts was 37.6+/-11.6% and was significantly higher than the value in 5-hr-preserved grafts (5.0+/-3.0%; P<0.01). However, OKY046 significantly reduced trypan blue uptake in 8-hr-preserved grafts (8.2+/-3.6%; P<0.01). Pancreatic tissue perfusion in 8-hr-preserved grafts after 2 hr of reperfusion was 28.5+/-7.5 ml/min/100 g, and was significantly lower than the value in 5-hr-preserved grafts (57.1+/-4.4 ml/ min/100 g; P<0.01), but OKY046 dramatically improved pancreatic tissue perfusion (97.1+/-14.6 ml/min/100 g; P<0.01). As a consequence, 8-hr-preserved grafts were resuscitated (4/5). We conclude that OKY046 protects the vascular endothelium during preservation by the two-layer method at 20 degrees C and consequently improves vascular microcirculation on reperfusion. Together with ATP synthesis, which is essential for repairing damaged cells, the canine pancreas graft subjected to 90 min of warm ischemia is resuscitated during 8-hr preservation by the two-layer method at 20 degrees C. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Adenosine↗

PubMed1996

Small bowel preservation using a cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

Preservation of the small bowel by a cavitary two-layer (University of Wisconsin solution [UW]/perfluorochemical) cold storage method was evaluated in the heterotopic rat segmental small bowel transplant model. Simple cold storage UW was effective only for 24-hr preservation. However, the cavitary two-layer method using UW made it possible to prolong preservation time up to 48 hr. Furthermore, without oxygen bubbling, the cavitary two-layer method was not effective for 48-hr preservation. Histologic studies of grafts preserved by the cavitary two-layer method for 48 hr at 7 days after transplantation showed normal architecture of the intestinal mucosa. This study demonstrates that the oxygenation of the small bowel during preservation by the cavitary two-layer method using UW makes it possible to extend preservation time up to 48 hr in the heterotopic rat segmental small bowel transplant model.

Adenosine↗

PubMed1996

Resuscitation of ischemically damaged pancreas during short-term preservation at 20 degrees C by the two-layer (University of Wisconsin solution/perfluorochemical) method.

We have shown that 24-hr preservation by a two-layer (University of Wisconsin solution [UW]/perfluorochemical [PFC]) cold storage method allows tissue ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. The purpose of this study was to examine whether increasing preservation temperature to 20 degrees C makes it possible to shorten a preservation period for recovery of ischemically damaged pancreas grafts. After 90 min of warm ischemia, canine pancreas grafts were preserved using the two-layer (UW/PFC) method for 1 to 8 hr at 20 degrees C, and then autotransplanted. A K-value of intravenous glucose tolerance test more than 1.0 at 2 weeks after transplantation was considered graft survival. ATP tissue levels were measured by high performance liquid chromatography at the end of preservation. Pancreatic tissue perfusions were measured using an H2 clearance technique after 30 min to 4 hr of reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5, control group). However, 3- and 5-hr preservations made it possible to recover the ischemically damaged pancreas (3/5 and 5/5, respectively), although 1- and 8-hr preservations were not successful (0/3 and 0/3, respectively). ATP tissue levels in 1-hr-preserved grafts were 2.55 +/- 0.38 mumol/g dry weight and were significantly lower compared with the levels in 5- and 8-hr-preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 (P < 0.01), respectively. On the other hand, pancreatic tissue perfusions in 8-hr-preserved grafts after 2 hr of reperfusion were 28.50 +/- 7.52 ml/100 g/min and were significantly lower than the values in 1- and 5-hr-preserved grafts, 66.0 +/- 11.22 (P < 0.01) and 57.10 +/- 4.40 (P < 0.01), respectively. It was suggested that 1-hr-preservation was not enough to synthesize ATP, which was essential to repair damaged cells, although vascular microcirculation at reperfusion was maintained and 8-hr preservation incurred microcirculatory disturbances, although ATP for repairing damaged cells was synthesized. We conclude that 3- to 5-hr preservation at 20 degrees C by the two-layer (UW/PFC) method accelerates ATP synthesis, which is essential for repairing damaged cells and protects vascular microcirculation. This makes it possible to resuscitate ischemically damaged pancreases faster. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

Adenosine↗

PubMed1996

Biliary-enteric anastomosis by means of a single layer of serosubmucosal sutures without T-tube drainage.

BACKGROUND: To lessen anastomotic stricture after biliary-enteric anastomosis, we developed a new biliary-enteric anastomosis that uses a single layer of interrupted serosubmucosal sutures without T-tube drainage. OBJECTIVE: To evaluate the safety and reliability of this new technique in a canine model of choledochoduodenostomy. METHODS: In 10 beagles, the common bile duct (2 to 3 mm in diameter) was ligated close to the duodenum with 3-0 polyglactin. On the fifth day after operation, the serum bilirubin level was elevated (137 to 205 mumol/L [8 to 12 mg/dL]) and the bile duct was dilated. The anastomosis between serosubmucosal layers of the dilated bile duct (8 to 10 mm in diameter) and duodenum was accomplished with interrupted sutures of 6-0 polyglactin with two needles. Stitches were inserted in the submucosal plane at the cut edge of the duct and duodenum to appose the mucosa accurately and to avoid accidental perforation of the entire thickness of the duct and duodenum. A T tube was not placed. RESULTS: There was no anastomotic leakage and the bilirubin level was normalized (14 to 17 mumol/L [0.8 to 1.0 mg/dL]) 7 days after operation for anastomosis. Histologic examination of specimens removed 6 or 12 months after operation showed good connective-tissue union and good mucosal continuity between the bile duct and the duodenum. There was no mucosal scarring and contracture or stricture formation. CONCLUSION: This new technique is simple and reliable and is recommended as an alternative method for restoring the continuity between the bile duct and intestinal tract after operation for obstructive jaundice caused by benign and malignant stricture of the bile duct.

Animals↗

PubMed1996

Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions.

The pathogenesis of hepatitis C virus (HCV) infection is likely to be associated with viral replication in vivo, but little is known concerning the dynamics of HCV turnover. We performed serial measurements of serum HCV-RNA levels following orthotopic liver transplantation (OLT) in nine patients with HCV-positive cirrhosis. Serum HCV-RNA levels were determined by quantitative polymerase chain reaction before, immediately after, and for up to 1 month after OLT. There was a rapid decline in HCV-RNA levels from 3.1 +/- 1.3 x 10(5) copies/ mL (mean +/- SEM) preoperatively to 0.15 +/- 0.6 x 10(5) copies/mL on the first and 0.16 +/- 0.6 x 10(5) copies/mL on the second postoperative day (mean viral half-life, 4.0 +/- 0.5 h). Thereafter, HCV-RNA levels increased in all but one patient, and by postoperative day 8 reached 3.6 +/- 1.3 x 10(5) copies/mL, exceeding the preoperative levels irrespective of the use or not of rescue immunosuppressive therapy including steroid bolus administration. In most patients, serum virions continued to increase averaging 11.6 +/- 2.8 x 10(5) copies/mL on the 30th postoperative day. These findings indicate that the half-life of HCV is quite short, and that extrahepatic viral replication contributes little to the total virus pool in serum. Furthermore, the marked HCV replication beginning as early as the third postoperative day strongly suggests that the liver graft is rapidly reinfected by HCV after OLT.

Adult↗

PubMed1996

Pharmacokinetics of intravenous adriamycin for anhepatic chemotherapy during liver transplantation.

Frequent recurrence of hepatocellular carcinoma after liver transplantation indicates the necessity to eliminate patients with advanced disease and combine transplantation with some form of perioperative adjuvant chemotherapy. This study was undertaken to elucidate adriamycin pharmacokinetics for anhepatic chemotherapy during liver transplantation. beagles of both sexes were allocated into two groups, controls (n = 4) and anhepatic animals with total hepatectomy under venovenous bypass (n = 5). In both groups, adriamycin was administered in 1 min at a dose of 1 mg/kg through the left antecubital vein and peripheral blood was obtained at intervals for up to 2 h to determine the plasma adriamycin levels. The animals were then sacrificed to determine tissue adriamycin levels in the liver, kidney, heart, lung, and skeletal muscle. Plasma adriamycin levels in anhepatic animals were significantly higher than those in controls at all measured time points after 10 min, resulting in a 50% reduction of the mean total body clearance of adriamycin compared with controls (P < 0.01). However, there was no statistically significant difference in adriamycin levels between the two groups for all measured tissues except for the liver. Despite the complete lack of hepatic function, anhepatic animals showed only a 50% reduction in total body clearance of adriamycin compared with normal controls, probably due to compensatory excretion from other organs such as the kidney. These results suggest that systemic chemotherapy with the standard dose of adriamycin may be tolerable during the anhepatic period of liver transplantation with enhanced tumoricidal effects on micrometastases.

Animals↗