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S Benz

Publications and source records attributed to S Benz.

52 records · Page 3Linked to original sources
PubMed1998

Ischemia/reperfusion injury of the pancreas: a new animal model.

BACKGROUND: Ischemia/reperfusion is thought to play an important role in the development of postimplantation pancreatitis after pancreas transplantation and also in the transition of edematous pancreatitis into necrotizing pancreatitis. Previous studies have suggested that impairment of microcirculation and hence tissue oxygenation and energy metabolism may be critical steps in this process. MATERIALS AND METHODS: In landrace pigs vascular isolation of the pancreatic tail was performed. Morphological alterations, tissue oxygenation, and energy metabolism were assessed in response to 3 h of global warm ischemia and the following reperfusion. RESULTS: A rapid onset of morphological alterations immediately after reperfusion was noted. Oxygen consumption and ATP levels were markedly decreased, and tissue oxygenation was severely impaired especially during the first hour after reperfusion. ATP tissue levels and oxygen consumption 10 min after reperfusion correlated significantly with the morphological changes at the end of the experiment. CONCLUSION: These findings can be explained by a failure of nutritive capillary perfusion and concomitant shunt perfusion. Therefore an impaired microcirculation rather than an impaired oxygen utilization shortly after reperfusion is of major relevance in the development of the ischemia/reperfusion injury of the pancreas.

Adenine Nucleotides↗
PubMed1998

Impairment of pancreatic microcirculation in the early reperfusion period during simultaneous pancreas-kidney transplantation.

The most likely cause of graft pancreatitis is the ischemia/reperfusion injury which can be a major problem in simultaneous pancreas-kidney transplantation. Animal experiments suggest the important role in this process of an impaired microcirculation after reperfusion. We have investigated pancreatic microcirculation in the early reperfusion period during clinical pancreas-kidney transplantation. Tissue PO2 (PO2ti) was monitored by a PO2-sensitive electrode. After reperfusion (a.r.) samples were taken from the venous effluent of the pancreas and simultaneously from the radial artery. After an initial peak a transient fall of PO2 was found. Total blood flow and hemoglobin oxygen saturation (sHbO2) in the venous effluent increased until 90 min a.r. (107 ml/min, 97.1%) High venous sHbO2 and high PO2ti correlated with good graft outcome. These findings can be explained by an impairment of capillary perfusion (no reflow) and concomitant shunt perfusion. The data suggest the considerable relevance of pancreatic microcirculation in the early reperfusion period during clinical pancreas transplantation.

Humans↗
PubMed1998

[Influence of the extrinsic nervous system on exocrine pancreatic secretion in the human].

Exocrine pancreatic secretion is regulated by gastrointestinal hormone and the autonomic nervous system. The interaction of both systems is still unclear. In humans CCK mediated regulation of exocrine pancreatic secretion requires a cholinergic tonus. The CCK receptor is thought to be localized on the acinuscell and modulated by cholinergic neurons. Pancreas transplantation and percutaneous diversion of the pancreatic juice offers the opportunity to investigate pancreatic secretion under the condition of complete extrinsic denervation. In the present study the influence of denervation on exogene CCK stimulation and simultaneous cholinergic stimulation or suppression with atropine, respectively, was investigated. CCK stimulation alone showed a reduced, dose dependent increase in enzyme secretion. Simultaneous stimulation with bethachenol resulted in a 2-fold increased secretion. Atropine suppressed the low dose CCK effect completely. Whereas CCK at high doses caused a 1.5 fold increase despite atropine. After extrinsic denervation the human pancreas remains sensitive to exogene stimulation. The intrinsic system remains also intact and is sensitive to cholinergic stimulation. The extrinsic nervous system seems to be necessary for an adequate CCK response. The results are in line with the hypothesis that CCK receptors are only partly localized on the acinuscell, whereas the majority is localized in extrinsic cholinergic neurons.

Adult↗
PubMed1998

[Initial applications of a new trochar system for non-laparoscopic intraluminal surgery].

Instruments that have been used in flexible endoscopy have always been confined to the working channel of the endoscope. We have therefore developed a device that allows transabdominal manipulation in the stomach under gastroscopic control with a device similar to a percutaneous endoscopic gastrostomy (PEG). For the first clinical application of this device it was used in order to perform pseudocystogastrostomy in patients with pancreatic pseudocysts.

Drainage↗
PubMed1996

Liposoluble antioxidants are not consumed in the pancreas after reperfusion in human simultaneous pancreas-kidney transplantation.

There is considerable evidence that under experimental conditions, oxygen free radicals (OFRs) are decisive in the pathogenesis of ischemia-reperfusion injury. Normally OFRs are scavenged by antioxidants such as alpha-tocopherol. Thus, in the following study we investigated whether antioxidants are consumed locally in human pancreatic grafts after reperfusion. A series of ten patients receiving bladder-drained pancreaticoduodenal and renal allografts were studied. Sequential blood samples were drawn locally from the venous outflow of the graft and simultaneously from the radial artery after reperfusion. alpha-Tocopherol, retinol, lycopene, and alpha- and beta-carotene levels were determined. After reperfusion these levels remained largely unchanged. Hence, in our study a consumption of antioxidants locally in the pancreatic graft after transplantation was not demonstrated. Therefore, the antioxidant capacity seems not to be exhausted at that time. This suggests that in clinical pancreatic transplantation oxidant stress in the initial reperfusion period might not have the relevance suggested by animal models.

Antioxidants↗
PubMed1996

Determinants of a normal (versus impaired) oral glucose tolerance after combined pancreas-kidney transplantation in IDDM patients.

After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i.v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p < 0.0001; C-peptide p = 0.037). Age (p = 0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (alpha-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (-46%; p = 0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p = 0.026), but not with HLA-AB-mismatches (p = 0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mis-matches.

Adult↗
PubMed1994

Simultaneous pancreas/kidney transplantation--the optimal therapy for type I diabetics with end-stage renal disease in Europe, too?

Contrary to the situation in the USA, the number of pancreatic transplantations declined during the last year in the Eurotransplant region. Whether the high postoperative morbidity and unsatisfactory graft function rates reported by many European centres can be overcome was investigated in a single centre study. In a consecutive series of 80 patients with simultaneous pancreas/kidney transplantations, postoperative morbidity due to graft pancreatitis and recurrent rejections was significant. Both of these complications, however, were treated successfully in the vast majority of patients. Graft thrombosis was almost completely prevented. Excellent function rates of the pancreatic grafts of 88% after 1 year and 83% after 5 years were achieved. Thus, simultaneous pancreas/kidney transplantation can be recommended as the optimal therapy for type I diabetics with end-stage renal disease in Europe, too.

Adult↗
PubMed1991

Current recording from sensory cilia of olfactory receptor cells in situ. II. Role of mucosal Na+, K+, and Ca2+ ions.

Action potential-driven current transients were recorded from sensory cilia and used to monitor the spike frequency generated by olfactory receptor neurons, which were maintained in their natural position in the sensory epithelium. Both basal and messenger-induced activities, as elicited with forskolin or cyclic nucleotides, were dependent on the presence of mucosal Na+. The spike rate decreased to approximately 20% when mucosal Na+ was lowered from 120 to 60 mM (replaced by N-methyl-D-glucamine+), without clear changes in amplitude and duration of the recorded action potential-driven transients. Mucosal Ca2+ and Mg2+ blocked spike discharge completely when increased from 1 to 10 mM in Ringer solution. Lowering mucosal Ca2+ below 1 mM increased the spike rate. These results can be explained by the presence of a cyclic nucleotide-dependent, Ca(2+)-sensitive cation conductance, which allows a depolarizing Na+ inward current to flow through the apical membrane of in situ receptor cells. A conductance with these properties, thought to provide the receptor current, was first described for isolated olfactory cells by Nakamura and Gold (1987. Nature (Lond.). 325:442-444). The forskolin-stimulated spike rate decreased when l-cis-diltiazem, a known blocker of the cyclic nucleotide-dependent receptor current, was added to the mucosal solution. Spike rate also decreased when the mucosal K+ concentration was lowered. Mucosal Ba2+ and 4-aminopyridine, presumably by means of cell depolarization, rapidly increased the spike rate. This suggests the presence of apical K+ channels that render the receptor cells sensitive to the K+ concentration of the olfactory mucus. With a slower time course, mucosal Ba2+ and 4-aminopyridine decreased the amplitude and caused rectification of the fast current transients (prolongation of action potentials). Abolishment of the apical Na+ current (by removal of mucosal Na+), as indicated by a strong decrease in spike rate, could be counteracted by adding 10 mM Ba2+ or 1 mM 4-aminopyridine to the mucosal solution, which re-established spiking. Similarly, blockage of the apical cation conductance with 10 mM Ca could be counteracted by adding 10 mM Ba2+ or by raising the mucosal K+ concentration. Thus mucosal concentrations of Na+, K+, and Ca2+ will jointly affect the sensitivity of odor detection.

Animals↗
PubMedDate not supplied

Organ procurement in experimental pancreas transplantation with minimal microcirculatory impairment.

BACKGROUND: Ischemia-reperfusion injury has been shown to deteriorate microcirculation in experimental pancreas transplantation. However, minor concern was taken on the impact of organ procurement in this condition. We examined the impact of a standardized technique of organ procurement on microcirculation and apoptosis in experimental pancreas transplantation. METHODS: Male Lewis rats were divided into three groups: sham-operated animals without dissection of the pancreas served as controls (n = 5); animals undergoing nearly total process of organ procurement with the pancreas pedunculated on the aorta and the hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal transplantation. Pancreatic grafts were preserved for 6 h in cold University of Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched controls, microcirculation was assessed by means of intravital fluorescence microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of acinar cells were detected by in situ nick end-labeling (TUNEL assay). The apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by microscopic counting of at least 50 hpf. RESULTS: Assessment of functional capillary density (FCD) in animals undergoing subtotal process of organ procurement revealed a slight non-significant decrease at 1 and 2 h compared with controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well as the apoptotic index were found slightly increased after organ procurement compared with controls (p > 0.05). However, after pancreas transplantation the apoptotic index and the LAV were significantly increased and the FCD significantly decreased compared with both groups of non-transplanted animals (p < 0.01). CONCLUSIONS: Our validated technique of organ procurement does not negatively impact microcirculation and apoptosis in experimental pancreas transplantation.

Anastomosis, Surgical↗
PubMedDate not supplied

Exogenous and endogenous nitric oxide donors improve post-ischemic tissue oxygenation in early pancreatic ischemia/reperfusion injury in the rat.

INTRODUCTION: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated. METHODS: IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage. RESULTS: The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05). CONCLUSIONS: The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI.

Animals↗