Effects of adenosine on ischaemia-reperfusion injury associated with rat pancreas transplantation.

BACKGROUND: During cold preservation, cellular consumption of adenosine triphosphate leads to the accumulation of nucleotides and nucleosides. The precise role of adenosine in modulating the inflammatory response of cold-preserved pancreas after reperfusion remains to be elucidated. The aim of this study was to assess the influence of adenosine on the inflammatory response associated with the process of ischaemia-reperfusion in rat pancreas transplantation. METHODS: The effect of adenosine from preservation solution on the levels of high-energy nucleotides and their breakdown products after cold ischaemic preservation was determined. In addition, the inflammatory response associated with the process of ischaemia-reperfusion in pancreas transplantation was quantified with and without pretreatment with the adenosine antagonist theophylline, and during preservation of the organ in University of Wisconsin solution with and without adenosine. RESULTS: Adenosine from preservation solution is able to modify the nucleotide and nucleoside content of preserved pancreas, indicating that adenosine is incorporated and metabolized in tissue. Administration of the adenosine antagonist to transplanted rats moderated the increases in nitrite and nitrate, myeloperoxidase activity and lipoperoxidation levels in the pancreas. CONCLUSION: Adenosine in the preservation solution may enhance the inflammatory response in rat pancreas transplantation.

Endothelin mediated nitric oxide effects in ischemia--reperfusion associated with pancreas transplantation.

Formation of nitric oxide (NO) in ischemia-reperfusion (I-R) associated with pancreas transplantation could modulate the inflammatory response. In this sense, previous studies have demonstrated the action of NO on vasoactive substances like prostacyclin or endothelin. The present study was designed to evaluate the contribution of endothelin to the inflammatory events induced by NO in the I-R process associated with pancreas transplantation. For this purpose, pancreatic levels of endothelin, neutrophil infiltration, and prostacyclin were evaluated in an experimental model of pancreas transplantation after inhibition of NO synthesis or after NO inhibition plus addition of endothelin. Results show significant posttransplantation increases in endothelin, neutrophil infiltration, and prostacyclin production. These increases were prevented by NO inhibition. Endothelin administration plus nitric oxide inhibition reversed this effect, resulting in an increase in myeloperoxidase and 6-keto-prostaglandin F1alpha. These results suggest that the proinflammatory effects of NO in I-R associated with pancreas transplantation are mediated by the induction of endothelin generation.

Balloon versus patch angioplasty as an adjuvant treatment to surgical thrombectomy of hemodialysis grafts.

BACKGROUND: Transluminal balloon angioplasty offers advantages to patch angioplasty. We evaluated the primary patency of thrombosed hemodialysis grafts that had undergone balloon angioplasty versus patch angioplasty as a salvage method. METHODS: We reviewed our experience with 22 consecutive intraoperative balloon angioplasties that were done in a 6-months period. The balloons used were noncompliant high pressure balloons. The balloon results were compared with those of 22 patients who had undergone patch angioplasties by the same surgeons. Age, gender, average time between graft insertion and revision, and number of prior revisions were analyzed. The two groups (patch and balloon) had similar ages (57 versus 58 years, respectively), gender distribution (12 women, 11 men versus 11 women and 11 men), average time of revisions before that particular procedure (15 versus 12 months), and average times of revisions before that procedure. RESULTS: Primary patencies of the patch and balloon group were respectively 86% versus 77% at 1 month, 45% versus 40% at 3 months, and 17% versus 28% at 6 months. There was no statistically significant difference between the two groups. Complications were comparable in both groups. CONCLUSION: Balloon angioplasty offers advantages to patch angioplasty, and we have shown similar patency rates. We recommend balloon angioplasty as a comparable method to salvage dialysis access grafts.

Nitric oxide enhances endothelin production in pancreas transplantation.

The role of endothelin and its relationship with nitric oxide (NO) production in ischemia-reperfusion associated with pancreas transplantation has been explored. For this purpose, pancreatic levels of endothelin were evaluated in an experimental model of pancreas transplantation after different periods of cold preservation. The effects of NO synthase inhibition were also evaluated. Results show posttransplantation increases in lipase and endothelin production. The release of lipase and endothelin was only prevented by NG-nitro-L-arginine methyl ester after a short ischemic period. Thus, endothelin synthesis could be a consequence of stimulation with NO in the ischemia-reperfusion associated with pancreas transplantation.

Differential effect of nitric oxide inhibition as a function of preservation period in pancreas transplantation.

The role of nitric oxide, produced during reperfusion as a function of preservation time, in the development of the inflammatory process in pancreas transplantation has been explored. For this purpose, the effect of nitric oxide synthase inhibition, as well as 6-keto-prostaglandin F1alpha, leukotriene B4, and lipoperoxidation levels were evaluated in an experimental model of rat pancreas transplantation after different periods of cold preservation. The results show posttransplantation increases in 6-keto-prostaglandin F1alpha, leukotriene B4, and lipoperoxidation levels in pancreatic tissue and in plasma lipase. When ischemia was induced for 30 min, nitric oxide synthase inhibition prevented these increases, and L-arginine was able to reverse this effect. By contrast, nitric oxide synthase inhibition has no effect when ischemia was prolonged for 12 hr. In summary, this study suggests that, during reperfusion, nitric oxide modulates 6-keto-prostaglandin F1alpha synthesis, lipoperoxidation levels, and the development of pancreatic injury but only when the ischemic period is quite short.

Long-term pancreas allograft outcome in simultaneous pancreas-kidney transplantation: a comparison of enteric and bladder drainage.

BACKGROUND: The optimal pancreatic exocrine drainage method remains controversial. Bladder drainage (BD) is widely used, but associated with a high incidence of urological complications (acidosis, dehydration, pancreatitis, and urinary tract infection). Enteric drainage (ED) avoids this morbidity, but may be associated with inferior graft survival. METHODS: We conducted a retrospective study comparing BD and ED in 71 simultaneous pancreas-kidney transplant recipients (37 BD; 34 ED) transplanted between February 1988 and June 1996. RESULTS: Five BD and five ED patients experienced early pancreas loss within 3 months after transplantation. The mean follow-up of the remaining 61 patients has been 45.7+/-3.9 and 76.0+/-3.3 months for ED and BD patients, respectively (P<0.005). Both groups had similar pretransplant demographics, co-morbidity, and nutritional and immunological status. The incidence of volume depletion (3.4% vs. 34.3%), acidosis (0% vs. 41.0%), pancreatitis (3.4% vs. 39.7%) and urinary tract infection (26.7% vs. 71%) was lower in ED patients (P<0.005 vs. BD). Of the BD group, 18.7% required conversion to ED for intractable complications. Initial length of stay was equivalent (17.7+/-9 days vs. 18.4+/-10 days) between groups. However, the number of admissions (0.79+/-0.18 vs. 1.38+/-0.14) and in-hospital days/patient/year (6.26+/-1.16 vs. 11.46+/-2.12) was less in ED patients (P<0.05 vs. BD). Actuarial patient and pancreas allograft survival up to 4 years after transplant was similar between groups. CONCLUSIONS: Compared with BD, (a) perioperative morbidity is not increased by ED, (b) ED is associated with fewer complications and hospitalizations, and (c) ED is not associated with increased long-term pancreas graft failure. These data suggest that ED is superior to BD and should be considered as the preferred technique for simultaneous pancreas-kidney transplants.

Intramedullary plasmacytoma in an unusual location in a renal transplant patient.

Transplant patients have increased risk for developing neoplasia. This is due to the use of more potent and long-term immunosuppression. We report a case of a 46-year-old man with a cadaver renal transplant who developed an intramedullary plasmacytoma in an unusual location. The patient had a total right elbow replacement and received 4 weeks of local radiotherapy. The pain completely resolved and the low-dose immunosuppression was continued.

Management of ureteral stenosis after renal transplantation.

BACKGROUND: Ureteral stenosis is the most common urologic complication of renal transplantation. Preferred management options for this complication vary among centers. Ureteral stenosis occurred in 24 (3.4 percent) of 692 consecutive renal transplants. The diagnosis was confirmed by antegrade pyelography after ultrasonography in all instances. An attempt was made to treat all patients by percutaneous stenting, usually with dilatation of the ureter, which was possible in 21 patients. In three patients, a wire could not be passed across the stricture and these patients were treated surgically. STUDY DESIGN: The patients were divided into two groups. Patients in group 1 (14 patients) presented within three months from the date of transplantation and patients in group 2 (seven patients) presented after three months. RESULTS: The site of stenosis was the ureterovesical junction in 80 percent of the patients and the uretero-pelvic junction in 20 percent. Urinary tract infection occurred in 70 percent of the patients in group 1 and 100 percent of patients in group 2. The success rate of percutaneous stenting was 71 percent (ten of 14 patients) in group 1, but only 29 percent (two of seven patients) in group 2. The failures were treated by repeated stenting (one patient in each group) or by operation. One allograft (7 percent) was lost in group 1 and two (28 percent) were lost in group 2. The average follow-up period was 38 months in group 1 and 56 months in group 2. There was no mortality in this series. CONCLUSIONS: Ureteral stenosis in the early postrenal transplant period can be safely and effectively treated by percutaneous dilatation and stenting, with few side effects and long-term success. This method is specially efficacious in patients who present within three months from the time of their transplant. In patients who have ureteric strictures developing after three months from transplantation, percutaneous stenting is of limited value and most patients require surgical correction.

Arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation.

The implication of eicosanoid metabolism and its relationship with oxygen free radical production in the process of ischemia-reperfusion associated with rat pancreas transplantation has been explored in this study. For this purpose male Sprague-Dawley rats were classified as follows: group I, control animals not surgically manipulated; group II, pancreas transplantation, after 30 min preservation in UW solution; group III, pancreas transplantation after 12 h preservation under the same conditions; group IV, same as group III but with administration of SOD 5 min prior to organ revascularization. The results show post-transplantation increases in 6-keto-PGF1 alpha, TXB2, LTB4 and 12-HETE in pancreatic tissue independent of preservation time. The fact that SOD administration could reverse these increases even though an efficient xanthine oxidase irreversible inhibitor such as allopurinol was present in the preservation solution suggests that eicosanoid generation in the recipient rat would be mediated by an oxygen free radical dependent mechanism not exclusively dependent on endothelial xanthine oxidase activity.

Insulin receptor down-regulation and impaired antilipolytic action of insulin in diabetic patients after pancreas/kidney transplantation.

Patients with insulin-dependent diabetes who receive pancreas/kidney transplants lose their need for insulin injections, but they become hyperinsulinemic and insulin resistant, and sometimes develop noninsulin-dependent diabetes mellitus. The reason for the insulin resistance is not well understood. Specifically, it is not known whether they become resistant to the action of insulin on lipid metabolism. Euglycemic-hyperinsulinemic clamps were performed in six pancreas/kidney (P/K) recipients, six kidney (K) recipients (to control for immunosuppressive therapy), and eight healthy controls. Measured were leg blood flow (by plethysmography), rates of lipolysis (with [2H5] glycerol), fatty acid oxidation (by indirect calorimetry), fatty acid reesterification (with [2H5]glycerol and [1-13C]palmitate), monocyte membrane insulin binding (with [125I]Tyr-A14 insulin), and insulin receptor mass (by RIA). Fasting plasma insulin concentrations were 2 times higher in P/K and K recipients (108 pmol/L) than in controls (54 pmol/L). Insulin receptor mass in solubilized monocyte membranes from P/K and K recipients was reduced by 61% and 63%, respectively, whereas insulin binding was reduced by 73% and 70%, respectively. P/K and K recipients were resistant to the inhibitory action of insulin on lipolysis (P/K vs. controls, P < 0.01; K vs. controls, P < 0.02) and on fatty acid reesterification (P/K vs. controls, P < 0.02; K vs. controls, P < 0.03). P/K recipients appeared to be more resistant than K recipients, but the differences between the two groups were not statistically significant. We conclude that P/K recipients were hyperinsulinemic, had down-regulated the number of their monocyte insulin receptors, and were resistant to the antilipolytic action of insulin.

Our experience with Roux-Y intestinal drainage in simultaneous kidney and pancreas transplantation.

Enteric drainage is a sound surgical technique in SKP, and it avoids the majority of urological as well as metabolic complications. We did not see an increase in intraabdominal complications or of graft loss due to rejection. Intestinal leak is rare and easily managed provided a Roux-Y loop of jejunum is used. Even though the number of patients was small and the follow-up short, the results of the RY group were at least comparable to the BD group. In view of our results, we plan to use this technique in all our future SKP patients.

Effect of a platelet-activating factor antagonist and desferrioxamine administration on eicosanoid production in rat pancreas transplantation.

Eicosanoid metabolism and its relationship with platelet-activating factor and oxygen free radical production in rat pancreas transplantation has been studied herein. Male Sprague-Dawley rats were classified in 4 experimental groups (n = 8 each) as follows: group 1, control; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 with desferrioxamine administration before revascularization of the organ in the recipient rat; and group 4, same as group 3 with administration of a platelet-activating factor antagonist (BN-52021). The results show post-transplantation increases in eicosanoid production in pancreatic tissue. The fact that desferrioxamine and BN-52021 administration could reverse increases in thromboxane B2, leukotriene B4, and 12-hydroxyeicosatetraenoic acid but only BN-52021 affected 6-keto-PGF1 alpha levels suggests the existence of a close relationship between platelet-activating factor and oxygen free radical in eicosanoid production in pancreas transplantation and it points to a differential role of metabolites produced by circulatory cells and endothelial cells.

Efficacy of local graft irradiation in preventing cadaveric renal transplant rejection: a prospective randomized trial.

Successful renal transplantation depends on the modification of the normal immunologic response. The earliest attempts at such modification involved the use of ionizing irradiation. The significant morbidity and mortality of total body irradiation led to its abandonment in favor of the safer technique of local graft irradiation. While still commonly used, the efficacy of this technique has never been evaluated in a prospective, randomized fashion. The present study is a prospective, randomized, double blinded evaluation of the efficacy of the addition of local graft irradiation to our immunosuppressive protocol. One hundred consecutive cadaveric renal transplants were randomized to receive either conventional immunosuppression alone or conventional immunosuppression plus local graft irradiation delivered in doses of 150 rads on the 1st, 3rd and 5th post-operative days. Patients were followed for a period of 2 years. No significant difference was demonstrated between the groups among any measured parameter. In conclusion, the addition of local graft irradiation in doses of 150 rads on d 1, 3, and 5 does not appear to offer any advantage over standard immunosuppressive therapy and its use cannot be recommended.

[Quality of life after liver transplant]. / Calidad de vida tras el trasplante hepático.

Hepatic transplant has recently undergone ostensible changes in post operative mortality. The present study investigates whether this improvement in survival is associated with a subjective and objective improvement in quality of life. Nineteen patients were evaluated preoperatively and/or postoperatively with a questionnaire (Nottingham Health Profile). The results showed a remarkable improvement in the quality of life of these patients, which became more marked after three months. The readaptation to work was good, considering the current state of our society. The mean yearly hospital stay was 12 days, distributed in three admissions mainly to perform hepatic biopsy.

Calculation of portal contribution to hepatic blood flow with 99mTc-microcolloids. A noninvasive method to diagnose liver graft rejection.

The portal contribution (PC) to hepatic blood flow was calculated in 13 liver graft patients and 13 normal volunteers. The method is based on the quantification and normalization of the liver and spleen activity after the administration of 7 mCi (259 MBq) of 99mTc microcolloid. Forty examinations were performed in liver grafts and 13 in normal subjects. The PC was significantly higher in normal native liver (64.0 +/- 3.0%) than in functioning grafts (58.8 +/- 3.1%). In acutely rejecting patients, PC was significantly lower (52.4 +/- 2.0%) than in functioning grafts and similar to that observed in cholangitis (53.5 +/- 0.7%). The PC increases again once rejection has resolved (57.3 +/- 2.6%). During hepatitis post-transplant PC values (59.7 +/- 3.4%) were similar to those observed in functioning grafts. Overall, PC values over 55% are very unlikely to be due to rejection.