Excellent results with small stents in coronary arteries have led endovascular therapists to their use in infrapopliteal vessels. However, to date no level I evidence exists to recommend primary stenting over infrapopliteal angioplasty alone. The aim of this randomized single-center trial was to compare their 1-year outcome. A total of 38 limbs in 35 patients with critical limb ischemia were randomized to angioplasty (22 pts) or primary stenting (16 pts). Target lesions were infrapopliteal occluded (36) or stenotic (20) lesions ranging from <2 to >15 cm in length. The mean age was 72 years. At 12 months, there was no statistical difference in survival (angioplasty, 69.3%; primary stenting, 74.7%), in limb salvage (angioplasty, 90%; primary stenting, 91.7%), or in primary and secondary patency (angioplasty, 66 and 79.5%; primary stenting, 56 and 64%) between the groups Renal insufficiency was the only significant negative predicting factor for limb salvage in both groups. In conclusion, the 1-year results for both groups were broadly similar. Stenting has its place in infrapopliteal angioplasty if the procedure is jeopardized by a dissection or recoil, but our results do not support primary stenting in all cases.
Acute rejection remains a major problem in simultaneous pancreas–kidney (SPK) transplant and occurs in 60–100% of the cases. With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving anti‐thymocyte globulin (ATG) or Basiliximab® induction therapy and cyclosporine Neoral® (CyA), MMF, steroid basis immunosuppression. Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean±standard deviation (SD) age of 42±6 yr. Of these, 14 patients were treated with anti‐thymocyte globulin (ATG) Fresenius® (rabbit) 3–5 mg/kg for 6±2 d, cyclosporine Neoral (CyA) (trough levels 350–400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect®, Novartis 20 mg on d 0 and d 4 post‐transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean±SD cold ischemia time (CIT) of the organs was 10.1±2.4 h for the pancreas and 10.5±2.6 h for the kidney. Results: Biopsy‐proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6‐d course of anti‐CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1±0.7% and serum creatinine with a mean of 1.24±0.24 mg/dL in a mean follow‐up period of 17±15 months (median 12, range 2–37). Conclusion: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas–kidney transplant (PKT) with a marked reduction in the incidence of rejection.
Pancreatic segmental autotransplantation in the pig has been considered an attractive model to study several aspects of pancreas transplantation because of the absence of rejections related to the immune system. However, the frequent presence of anatomical variations in the vascular supply of the left pancreatic segment in the pig makes this model difficult, impairing the access for vascular flushing and revascularization in pancreatic autotransplantation. We assessed pancreatic vascular anatomy of 71 Landrace pigs: group I (G1, n = 32) transplanted after direct reconstruction of the hepatic flow; and group II (G2, n = 39) transplanted after hepatic-celiac arterial reconstruction (HECAR) with an iliac vascular graft between the celiac trunk and the hepatic artery. HTK (histidine-tryptophan-ketoglutarate; Custodiol) and UW (University of Wisconsin; Viaspan) solutions were used. In total, 23 technically successfully transplanted animals (HTK = 15; UW = 8) after 24 h of cold storage were studied. Reconstruction time was longer in G2 than in G1 (p = .04). Thrombosis of the reconstructed hepatic artery occurred more in G1 than in G2 (45% vs. 8%, respectively, p = .013). Pancreatic arterial thrombosis was noticed in 10 animals in G1 (32%) and in 2 in G2 (5%) (p = .026). Ninety-four percent of pancreas grafts were suitable for cold storage study in G2 versus 45% for G1 (p < .001). No differences were noticed in K values, weight of transplanted grafts, preoperative and 24 h postoperative glycemia, for both preservation solutions. Segmental pancreatic autotransplantation can be successfully performed for cold preservation studies. A high percentage of pancreas useable for transplantation can be achieved using hepato-celiac arterial reconstruction. HTK solution is suitable for flushing and 24 h of preservation for pancreatic grafts in the porcine model.
Delayed graft function (DEGF) remains an obscure phenomenon in organ transplantation. For the optimal washing of the compounds of the different organ flush solutions, adequate temperature and equilibrium of electrolytes have to be provided. A total of 29 landrace pigs weighing 37.3–5.4 kg were included in this study. According to the model, the left hemipancreas was perfused with Histidine-Tryptophan-Ketoglutarate (HTK)-solution and autotransplanted after 24 h (G1, n = 13) and 48 h (G2, n = 4) of cold storage (CS). Results were compared with grafts perfused with UW-solution and autotransplanted after 24 h (G3, n = 8) and 48 h (G4, n = 4) CS respectively. Daily measurements of glycemia, glucosuria, amylase and lipase were carried out. HTK perfusion resulted in an increase in wet weight of the grafts after 24 h and 48 h CS (P = 0.031 vs UW). Postoperative glycemia levels in pancreases flushed with HTK-solution were higher after 48 h than after 24 h CS until the 6th postoperative day, when the glycemia returned to normal range (P = 0.02), suggesting a delayed endocrine graft function. The mean IVGTT values attained after full function were comparable in G1 and in G3 (–1.22 ± 0.23 vs. –1.5 ± 0.65). The rises in serum amylase and lipase levels were more pronounced after 48 h CS in both HTK and UW groups, (P = n.s.). Appearance of interstitial and intracellular edema after CS and reperfusion did not influence the function.Conclusion: HTK-solution is suitable for 24 h pancreatic preservation in vivo; the perfusion requires at least 4 min for electrolyte equilibration. Long preservation time (48 h) resulted in a transitory DEGF.
446 HTK (Histidine Tryptophan Ketogluterate) has been used for experimental and clinical cardiac, renal and liver transplantation. No experience exists in either experimental or clinical pancreas transplantation. Methods: In the present study the solution was employed to flush segmental pancreatic grafts and to autotransplant the grafts after 24, 48 and 72 hours of cold storage in a porcine model. The results were compared to those obtained from animals receiving pancreatic grafts flushed and preserved with UW (University of Winsconsin) solution. Results: A total of 10 landrace pigs received a graft stored with HTK solution for 24 hours and 6 animals received a graft stored with UW solution for 24 hours. Daily blood glucose levels were normoglycemic (i.e. bloodglucose < 150 mg/dl) and glucosuria was absent in all transplanted animals. Intravenous glucose tolerance tests (IVGTT) were comparable to 2 unoperated controls. Seven totally pancreatectomized not transplanted diabetic controls exhibited daily hyperglycemia, glucosuria (i.e. > 1 000 mg/dl) and highly impaired IVGTTs (mean K-values - 0.52 ± 0.19 vs - 1.25 ± 0.46 for HTK, - 1.30 ± 0.81 for UW and - 1.53 ± 0.81 for controls, p vs diabetic < 0.01). The changes in wet weight between flushing and reperfusion were +2.22 ± 2.84g for HTK and - 1.40 ± 2.70 g for UW stored grafts (p = 0.034). After 48 hours storage with HTK 4/17 grafts were functioning and 1/11 recipients of grafts stored with UW were normoglycemic. All grafts stored for 72 h in either HTK (n=3) or UW (n=3) uniformely failed to render the recipients normoglycemic. Conclusions: It is concluded that preservation of segmental pancreatic autografts for 24 hours with HTK solution provides reliable graft function as does preservation with UW solution associated with an increase in wet weight following HTK preservation. Cold preservation with HTK and UW is feasable for 48 hours, however the successrate is equally reduced with HTK and UW solution. 72 hours cold storage in either HTK or UW solution is resulting in uniform graft failure in this model.
Histidine Tryptophan Ketoglutarate (HTK) has been used for experimental and clinical cardiac, renal and liver transplantation in particular in the Eurotransplant setting. There is no data available for experimental or clinical pancreas transplantation. In the present study HTK was used for cold storage of pancreatic grafts and the results were compared to those obtained with UW solution.Methods: In a porcine model segmental pancreatic autografts were stored for 24, 48 or 72 hours in cold HTK or UW (University of Winsconsin) at 4 degrees C and then grafted into pancreatectomized diabetic recipients.Results: Landrace pigs (weighing 35-45 kg) were used for the study. Under general anesthesia a duodenum preserving total pancreatectomy was performed. The left hemipancreas was flushed through the aterial vascular pedicle with HTK or UW solution (50-100 cc, perfusion pressure of 60 cmH(2)O). Following storage of the graft for 24, 48 or 72 hours at 4 degrees C relaparotomy was performed and a heterotopic transplantation was performed to the iliac artery and vein. A total of 10/10 landrace pigs receiving a graft stored with HTK solution for 24 hours and 6/6 animals receiving a graft stored with UW solution for 24 hours were normoglycemic (i.e. bloodglucose < 150 mg/dl) and glucosuria was absent. Intravenous glucose tolerance tests (IVGTT) were comparable to 2 unoperated controls. Seven totally pancreatectomized not transplanted diabetic controls exhibited daily hyperglycemia, glucosuria (i.e. > 1000 mg/dl) and highly impaired IVGTTs (mean K-values -0.52 +/- 0.19 vs -1.25 +/- 0.46 for HTK, -1.30 +/- 0.81 for UW and -1.53 +/- 0.81 for controls, p vs diabetic < 0.01). The changes in wet weight between flushing and reperfusion were +2.22 +/- 2.84 g for HTK and -1.40 +/- 2.70 g for UW stored grafts (p = 0.034). Following 48 hours storage with HTK 4/17 grafts were functioning and 1/11 recipients of grafts stored with UW were normoglycemic. All grafts stored for 72 h in either HTK (n = 3) or UW (n = 3) uniformely failed to render the recipients normoglycemic.Conclusions: Preservation of segmental pancreatic autografts for 24 hours with HTK solution provides reliable graft function as does preservation with UW solution associated with an increase in wet weight following HTK preservation. Cold preservation with HTK and UW is feasable for 48 hours, however the successrate is equally reduced with HTK (23,5%) and UW (9%, p = ns) solution. 72 hours cold storage in either HTK or UW solution is resulting in uniform graft failure in this model.
Die University of Wisconsin (UW) Lösung wurde ursprünglich am Hundemodell für das Pankreas entwickelt [9]. Gegenwärtig wird die Lösung sowohl für Pankreas und Leber als auch für Nieren mit großem klinischen Erfolg eingesetzt [3,4].
Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model.Twelve pigs (weighing 28–35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups.Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups.On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia–reperfusion injury.
Background. Histidine-tryptophan-ketoglutarate (HTK) has been used for experimental and clinical cardiac, renal, and liver transplantation. No experience exists in either experimental or clinical pancreas transplantation.Methods. In the present study, the solution was employed to flush segmental pancreatic grafts and to autotransplant the grafts after 24, 48, and 72 hr of cold storage in a porcine model. The results were compared to those obtained from animals receiving pancreatic grafts flushed and preserved with UW (University of Wisconsin) solution.Results. A total of 10 landrace pigs received a graft stored with HTK solution for 24 hr, and 6 animals received a graft stored with UW solution for 24 hr. Daily blood glucose levels were normoglycemic (i.e., blood glucose <150 mg/dl), and glucosuria was absent in all transplant animals. Intravenous glucose tolerance tests were comparable to two unoperated controls. Seven totally pancreatectomized, nontransplant diabetic controls exhibited daily hyperglycemia, glucosuria (i.e., >1,000 mg/dl) and highly impaired intravenous glucose tolerance tests (mean K-values of -0.52+/-0.19 vs. -1.25+/-0.46 for HTK, -1.30+/-0.81 for UW, and -1.53+/-0.81 for controls, P-value vs. diabetic <0.01). The changes in wet weight between flushing and reperfusion were +2.22+/-2.84 g for HTK and -1.40+/-2.70 g for UW stored grafts (P=0.034). After 48 hr of storage with HTK, 4/17 grafts were functioning and 1/11 recipients of grafts stored with UW were normoglycemic. All grafts stored for 72 hr in either HTK (n=3) or UW (n=3) uniformly failed to render the recipients normoglycemic.Conclusions. It is concluded that preservation of segmental pancreatic autografts for 24 hr with HTK solution provides reliable graft function, as does preservation with UW solution associated with an increase in wet weight after HTK preservation. Cold preservation with HTK and UW is feasible for 48 hr; however, the success rate is equally reduced with HTK and UW solution. Cold storage for 72 hr in either HTK or UW solution results in uniform graft failure in this model.
Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model.Twelve pigs (weighing 28–35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups.Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups.On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia–reperfusion injury.