摘要:

The occurrence of biliary strictures in allografts following liver transplantation correlates with the duration of preservation time. The correlation between preservation time and biliary strictures suggests that anoxic or reperfusion injury of the bile duct epithelium causes stricture formation. However, the relative susceptibility of bile duct cells to anoxic or reoxygenation injury is unknown. Our aims were to determine the vulnerability of rat liver bile duct cells to anoxic and reoxygenation injury and to compare the results with hepatocytes. During anoxia, bile duct epithelial cells were significantly more resistant to cell killing than hepatocytes. Rates of cellular proteolysis were also 2.5-fold lower in bile duct cells than in hepatocytes during anoxia. In contrast to anoxia, reoxygenation of anoxic cells increased cell killing of bile duct cells but improved viability of hepatocytes. The rate of toxic oxygen species formation by bile duct cells was 5-fold greater than in hepatocytes during reoxygenation. In addition, basal levels of glutathione are lower in bile duct cells than in hepatocytes. These data suggest that bile duct cells are more susceptible to reoxygenation injury than to anoxia. These studies support the hypothesis that reoxygenation injury during liver preservation leads to bile duct injury during liver transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Pancreatic islets can be isolated from cold-preserved organs. They contain 60% more β cells when prepared from organs that were stored for 24 hr in Collins solution supplemented with albumin and benzamidine (CAB) instead of University of Wisconsin (UW) solution. Recovery from CAB-stored organs was similar when CAB was perfused in situ before organ removal or ex vivo after organ harvesting in UW. In situ flush with cold Ringers before ex vivo replacement by CAB resulted in 25% lower recovery of islet β cells and in higher contamination with nonendocrine and damaged cells. Recovery of β cells was 50% reduced when cold storage solution was not chased before collagenase digestion of the organ. It is concluded that the isolation of rat islets from cold-preserved organs can be improved by using UW or CAB instead of Ringers for situ perfusion, by cold storage in CAB, and by adequate chase of cold storage solution with physiologic medium before collagenase digestion. These conditions can be tested in current human islet isolation protocols.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Second-set rejection is generally considered to be mediated by cytotoxic humoral antibodies. A few discordant data have been reported, however. To address this question, we have taken advantage of a model in which specific cytotoxic alloantibodies are not produced although transplantation cellular immunity develops. Following a transplant of allogeneic stem cells from fetal liver, chimeric mice (BALB/c→CBA—i.e., H-2d→H-2k) were obtained; virtually all peripheral blood lymphocytes and spleen cells were of BALB/c donor origin. Anti-sheep red blood cell humoral response was present, although significantly lower in chimeras than in controls. These allochimeras were hyperimmunized by skin grafts and injections of spleen cells. The survival of skin grafts and the production of antibodies were then analyzed. When hyperimmunized against a third party, B6 (H-2b), chimeric mice were not able to raise a detectable humoral response involving anti-B6 cytotoxic antibodies, yet they rejected B6 skin allografts in an accelerated fashion (8.44±0.17 days). Control CBA mice rejecting second-set B6 skin grafts within the same delay developed high-titer, specific cytotoxic antisera (mean titer = 140). These data show that cytotoxic allospecific antibodies are not indispensable in the development of second-set accelerated rejection of skin allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The aim of this study was to ascertain whether, in an animal model, continuous monitoring of mesenteric venous pressure (MVP) via an indwelling mesenteric venous catheter could assist in early detection of thrombosis of the portal vein (PVT) and superior mesenteric artery (SMAT). The role of portography via the catheter was also studied in confirming these complications. An animal model of PVT and SMAT was developed in pigs. At laparotomy, a 20-cm jejunal loop was isolated and a heparin-coated catheter was inserted into a mesenteric vein of the isolated jejunum and connected to a pressure transducer. Conditions of PVT were simulated by progressive occlusion of the portal vein (PV) using a silastic tourniquet and those of SMAT by superior mesenteric artery (SMA) clamping. MVPs (mm Hg) were found to significantly increase with all degrees of PV occlusion (P< 0.01, Student'sttest) and to significantly decrease after SMA occlusion (P< 0.01). Portography clearly demonstrated all degrees of PV stenosis after PV occlusion and stasis of contrast medium during SMA occlusion. The authors feel that this method enables rapid diagnosis of PVT and SMAT and may be useful in the monitoring of the therapy for these complications after small bowel transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Significant atrophy and impaired absorption occur in the heterotopically transplanted small intestinal isograft, and these deficits are corrected when the preferred fuel of the enterocyte, glutamine (Gin), is supplemented to total parenteral nutrition (TPN). In the orthotopic small bowel isograft, this study determined whether Gin-enriched TPN enhanced mucosal structure and function, and decreased bacterial translocation to mesenteric lymph nodes (MLN). Seventeen adult Lewis rats received orthotopic jejunal isografts and central venous catheters for TPN. Rats received either TPN with 2% Gln or the same TPN with isonitrogenous balanced nonessential amino acids for 10 days. Eight normal, chow-fed rats served as baseline controls. Mucosal villous height, surface area, crypt depth, weight, protein and DNA contents, brush border enzymes,14C glucose absorption, and bacterial translocation to MLN were evaluated in both the graft and host jejunum and the control animals. Gin-enriched TPN significantly increased mucosal villous height (P< 0.01), surface area (P< 0.01), and glucose absorption (P< 0.01), and it reduced bacterial translocation (P< 0.05) when compared with the non-Gin TPN group. For most study variables, there were no significant differences between Gln-enriched TPN or baseline and between the graft and host jejunum for Gin- and non-Gln-supplemented animals. There were no significant differences in DNA content and brush border enzymes among groups. These results indicate that Gin-enriched TPN improves mucosal structure and glucose absorption and reduces bacterial translocation to MLN in the orthotopic small bowel isograft.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The aims of this study were to devise an omental pouch site for islet implantation in a preclinical large animal and to compare the function of islets engrafted to this site with islets implanted into the spleen. Highly purified islets were isolated from outbred mongrel dogs, then grafted into totally pancreatectomized outbred recipients. Autografts of islets were implanted into a greater omental pouch (group [gp] 1, n=12) or into the spleen by venous reflux (gp 2, n=12). Allografts of single donor islets were implanted into the omental pouch (gp 3) of dogs that received CsA (n=9) or untreated controls (n=3). The threshold islet mass that consistently reversed diabetes in gp 1 was 10 μl/kg, which exceeded by 2.5-fold that required in gp 2. Normoglycemia was induced and maintained for 2 months in 6 gp 1 and 8 gp 2 dogs. At IVGTT, the K value (decline in glucose, %/min) was 1.3±0.4 in gp 1 versus 1.5±0.2 in gp 2 (P>0.2). Peripheral venous insulin levels were significantly lower (P< 0.01) in gp 1. Omentectomy (gp 1) or splenectomy (gp 2) induced prompt hyperglycemia. All gp 3 dogs (received >10 μl/kg) were initially normoglycemic: grafts of untreated controls failed at 4.2±1.8 days. In 1 CsA-treated dog the graft failed for technical reasons; normoglycemia persisted in the other 8 for 10, 15, and 21 days, and in 5 instances for >30 days. When CsA therapy was stopped at 30 days, normoglycemia persisted for 34±9.5 days. We conclude that purified islets restore normoglycemia after implantation into the omental pouch of diabetic dogs. Compared with intrasplenic islet implantation, an increased graft volume is required and insulin levels are lower.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

CsA is a commonly used immunosuppressive drug known to possibly induce cholestatic side effects. Ursodeoxycholic acid (UDC), a nonhepatotoxic bile acid, has proved to be efficient for several types of cholestasis. The aim of this experiment was to evaluate the ability of tauroursodeoxycholate (TUDC) in preventing CsA-induced cholestasis on bile duct-cannulated rats. After bile flow stabilization, a bolus of 30 mg/kg CsA was given i.v. to one group (n=7) and was associated with a 2 μmol/kg/min TUDC infusion in another group (n=7). The control group was injected with CsA-solvent. CsA, as used here, had a rapid and marked cholestatic effect. However, both bile flow and bile salt secretion were significantly enhanced in the TUDC group when compared to the CsA alone-treated group and showed no difference with the solvent control group. In addition, TUDC significantly increased elimination of CsA and its metabolites in bile. In contrast to what was found for endogenous bile salts, TUDC uptake was not affected by CsA. The anticholestatic effect of TUDC probably resulted from preventing CsA-induced hepatocyte membrane damage and from easing biliary excretion of CsA. Such properties could be helpful for CsA-treated liver recipients who are especially exposed to cholestatic problems, and thus, to toxic CsA accumulation in the liver. Moreover, regulation of CsA elimination might prevent, in part, its general toxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n=29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n=17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID