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Biomedical subjects

N Senninger

Publications and source records attributed to N Senninger.

At least 19 recordsLinked to original sources

Hormonal control of opossum sphincter of Oddi motility: role of myoneural continuity to duodenum.

Motilin and caerulein are known to affect motility of the sphincter of Oddi (SO) and the gastrointestinal tract. The role of SO-duodenal myoneural continuity in the action of these peptides was studied. Five opossums had translocation of the duodenal papilla into the jejunum, while preserving the blood supply to the SO and duodenum. Serosal electrodes were placed in the SO, duodenum, and jejunum. Five control animals had electrode placement alone. Myoelectric recording was obtained during fasting and after administration of motilin (400 ng/kg) or caerulein (500 ng/kg/hr). Motilin induced premature phase III-like activity in the SO and intestine in controls. After the translocation of the papilla, the spike frequencies during phase II and phase III were significantly lower than in controls, whereas those during phase I and phase IV were not different. Motilin caused premature intestinal phase III and increased SO spike activity. However, the increase in SO spike activity was insufficient to form phase III. Caerulein produced a sustained increase in spike activity in both regions in both groups, but the increase was less in the translocation group than in controls. These data suggest that duodenal activity stimulated by motilin and caerulein participates in the activation of SO motility via intrinsic myoneural pathways.

Animals

Bile-induced pancreatitis.

The main bile-induced pancreatitis models are described with special attention to the duct injection models in dogs and the obstruction/reflux model in opossums. Practical problems of setup, study controls and monitoring are addressed. As for the opossum model, due to its clinical relevance the high variability of problems in the pathogenesis of pancreatitis that may be tackled by this model makes it a very useful, simple and not too expensive tool in the hands of a pancreatitis researcher.

Acute Disease

Advantages and disadvantages of using the hydrogen clearance technique to measure pancreatic blood flow.

This study was undertaken to identify the advantages and disadvantages of using the hydrogen clearance technique (HCT) to measure pancreatic blood flow (PBF) in the opossum over short and long periods. An open study was performed on 8 opossums. A total of 72 platinum electrodes were implanted into the pancreas. On the fifth day 41 additional electrodes were implanted. All implantation sites were examined histologically after five days. Measurements of pancreatic blood flow were taken every other day for five days. Three measurements were taken from each electrode and the mean of the three was used for analysis. In the anaesthetized animal mean PBF (SD) was 63.5 (12.8) ml min-1 100 g-1 immediately after electrode implantation and 34.3 (11.4) ml min-1 100 g-1 on the 5th postoperative day. Of the implanted electrodes, 35% failed during the experimental course, mainly as the result of proliferation of scar tissue around the electrodes. Mild to moderate fibroproliferation had taken place around the platinum tips of the remaining 65%. Primary electrode implantation caused no or negligible trauma to the pancreas. We recommend the HCT only for short-term measurements of PBF. Implantation of electrodes for any length of time leads to inflammatory changes around the platinum tips that cause proliferation of scar tissue and lead to failure of the electrodes, misleadingly low PBF recordings, and fewer monoexponential clearance curves.

Animals

[Liver transplantation after trans-jugular intrahepatic portosystemic stent shunt].

Every third patient with parenchymal liver disease bleeds from esophageal varices. Treatment of this complication is of special interest with regard to liver transplantation which may become necessary later on. The mesocaval H-shunt excluded, surgical shunting results in technical and hemodynamic problems during transplantation. They may be avoided by the new approach of transjugular intrahepatic portosystemic stent shunt (TIPSS). We report our experience with liver transplantation in two patients after TIPSS.

Adult

Arterial steal: an unusual cause for hepatic hypoperfusion after liver transplantation.

Case reports of two patients with an unusual cause for a rapid increase in transaminases following liver transplantation are described. In the postoperative course, angiography revealed an arterial hypoperfusion of the liver due to a steal phenomenon with blood shunting from the hepatic to the splenic artery. In one case, the underlying pathophysiology was a pre-existing filiform stenosis of the celiac trunk with insufficient recruitment of arterial blood from the superior mesenteric artery via the pancreatic arcade. Adequate liver perfusion was restored by simple ligation of the common hepatic artery. In the other case, angiography showed an arteriovenous fistula formation of the splenic vessels and minimal blood flow through the hepatic vessels. This was successfully corrected by angiographic embolization of the splenic artery with metal coils. After therapeutic intervention, both patients rapidly recovered with excellent liver function.

Adult

Sphincter of Oddi cyclic motility. Effect of translocation of the papilla in opossums.

The role of myoneural continuity between the sphincter of Oddi and duodenum in coordinating sphincter cyclic motility and the duodenal migrating myoelectric complex was studied in conscious opossums. Five animals underwent implantation of the duodenal papilla into the jejunum. Myoelectric recording was obtained from the sphincter, duodenum, and jejunum in these animals and from 5 other animals as controls. The mean spike frequency of the sphincter of controls was 1.6 per min during phase I, 4.2 per min during phase II, 11.0 per min during phase III, and 3.6 per min during phase IV of the duodenal migrating myoelectric complex. After translocation of the papilla, the spike rates during phase II (2.2 per min) and phase III (2.8 per min) were lower than in controls (p less than 0.02), while those during phases I and IV remained unchanged. Feeding disrupted the migrating myoelectric complex and increased sphincter spike activity in both groups; however, the plateau frequency after feeding was lower after the translocation. These data suggest that the duodenum does not control cyclicity of sphincter motility but sphincter-duodenal intrinsic myoneural continuity is important in the increase in sphincter spike activity during phases II and III and after feeding.

Ampulla of Vater

Prostanoid release in experimental liver transplantation.

Prostanoids are biologically active mediators of inflammation and tissue injury. To investigate the role of prostanoids in orthotopic liver transplantation we used a porcine model and determined prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in arterial, portal, and hepatic venous blood during organ harvesting, the recipient operation, and the early postoperative period. There were no significantly increased serum levels during the donor operation or at the end of cold storage. As early as 1 or 5 min after initiation of reperfusion of the transplanted organ, prostanoids in hepatovenous blood increased dramatically (100-500-fold). Changes in arterial and portal blood (10-50-fold) were less pronounced but still statistically significant. In surviving animals these values returned to normal within 24 hr. The hepatic release of metabolites of the arachidonic acid cascade after liver grafting indicates that the synthesis of prostanoids might contribute to morphological and functional alterations of the transplanted graft. In addition, the increased arterial values of circulating prostanoids may potentially participate in severe cardiovascular, hemostatic, and immunological alterations known to occur after liver transplantation.

6-Ketoprostaglandin F1 alpha

Evaluation of preservation damage after porcine liver transplantation by assessment of hepatic microcirculation.

The ischemic damage following liver transplantation (LTX) is predominantly located at the endothelial cell level and is a major cause for a disturbance of microcirculation. The present study was designed to test the hypothesis that changes in the quality of organ preservation are correlated with changes in microcirculation: 16 pigs underwent LTX, preservation by Bretschneider's HTK-solution (Histidin, Tryptophan, alpha-Ketoglutarat) complemented by indomethacin (50 mumol/L). Cold ischemia times were 9 hr (n = 8) and 18 hr (n = 8), respectively. Using the H2-clearance technique, hepatic microcirculation was measured before, 30 min, and 20 hr after LTX. Normal tissue perfusion was 107 +/- 16 ml/100 g/min, at 30 min posttransplantation 91 +/- 13 ml/100 g/min in the short-term and 48 +/- 7 ml/100 g/min in the long-term preservation group. Whereas no animal of the long-term preservation group survived longer than 8 hr, all animals of the short-term preservation group survived, and tissue perfusion could be measured 20 hr postoperatively (101 +/- 19 ml/100 g/min). At 30 min postoperatively, all surviving animals had tissue perfusion rates greater than 70, and all nonsurvivors had values below 60 ml/100 g/min. We conclude therefore that the extent of decrease of microcirculation after LTX may be a useful predictor of organ function and survival.

Alanine Transaminase

Effect of nifedipine on the motility of the sphincter of Oddi and small bowel of the opossum.

The effect of the calcium-channel blocker nifedipine on the electromyographic activity of the small bowel and sphincter of Oddi was studied in conscious opossums. Electromyographic and arterial pressure recordings were started 7-10 days after implantation of seven pairs of electrodes along the small bowel and sphincter of Oddi. Continuous infusion of nifedipine caused a dose-dependent reduction of the frequency of spike bursts in the small bowel and sphincter of Oddi. Nifedipine at high doses abolished the migrating motor complex in the gastrointestinal tract. The frequency of slow waves was unchanged. This drug possibly inhibits the membrane influx of calcium into the smooth muscle cells of the gastrointestinal tract. We conclude that nifedipine causes an intense decrease in the motility of the small bowel and sphincter of Oddi.

Ampulla of Vater

Intestinalization of pancreatic fragments in dogs: improvement in survival rate after acute segmental pancreatitis.

Intestinalization, a new method of pancreatic preservation in which vascularized pancreatic fragments are placed inside a jejunal pouch, has been tested for its effectiveness in the prevention of shock and death due to segmental pancreatitis. Intestinalization of the fragment resulted in the survival of eight of nine animals (89 percent) in which recovery was uneventful, whereas animals with pancreatitis in situ or in a mobilized fragment without intestinalization had a mortality rate of 100 percent within 2 days. We conclude that intestinalization ameliorates the outcome of hemorrhagic pancreatitis in the pancreatic fragment by effectively draining toxic products. The procedure may also be useful in pancreatic transplantation since no reintervention is necessary if graft failure or rejection occurs because the pancreas is accessible by endoscopy.

Animals

Gastrointestinal motility following small bowel obstruction in the opossum.

The motility of the gastrointestinal tract of six opossums with total and four with partial small bowel obstruction was evaluated. Following the establishment of small bowel obstruction, the migrating myoelectric complex was substituted by a new pattern which was characterized by periods of intense spike activity interspersed with quiescent periods. In the experiments with total intestinal obstruction, the frequency and duration of the periods of intense spike activity were related to the recording site and the time after establishment of intestinal obstruction. The frequency of spike bursts in the ileum proximal and distal to the obstruction was the greatest in the first 2 days after the establishment of the obstruction, while in the antrum and proximal small bowel, the frequency of bursts of spike potentials increased gradually from the first to the fourth postobstruction day (P less than 0.01). However, there was no change in the frequency, duration, and localization of periods of intense spike activity during the 5 days following the establishment of partial intestinal obstruction. We concluded that following intestinal obstruction, the migrating myoelectric complex is substituted by a myoelectric pattern that is characterized by periods of intense spike activity interspersed with quiescent periods. In the animals with total intestinal obstruction, the periods of increased motility are initially more frequent in the bowel proximal and distal to the obstruction and afterwards in the stomach and upper small bowel.

Animals

Effect of analgesic drugs on the electromyographic activity of the gastrointestinal tract and sphincter of Oddi and on biliary pressure.

Continuous biliary pressure and electromyographic activity of the sphincter of Oddi and gastrointestinal tract were recorded in conscious opossums following administration of analgesic drugs. Morphine, meperidine, and pentazocin increased significantly the duration of the migrating motor complex (MMC) cycle. Periods of 1-2 minutes of intense burst of spike potentials were seen in the sphincter of Oddi and duodenum following administration of morphine (8 experiments), meperidine (6 experiments), and pentazocin (3 experiments). The biliary pressure in the control studies was similar to that following administration of all analgesics in the animals with gallbladder and following instillation of tramadol, metamizol, and acetylsalicylic acid in animals with no gallbladder. However, the biliary pressure was significantly higher following administration of morphine, meperidine, and pentazocin in the animals with no gallbladder. It is concluded from this study that morphine, meperidine, and pentazocin may cause important disturbances in the motility of the sphincter of Oddi and gastrointestinal tract. These myoelectric disturbances may cause an increase in the biliary pressure in animals that have been subjected to cholecystectomy, but not in animals with intact gallbladder. The gallbladder may accommodate the bile produced by the liver during periods of sphincter of Oddi dysfunction and thus impede an increase in the biliary pressure.

Ampulla of Vater

Intestinalization of pancreatic fragments in dogs.

A new operative procedure for the preservation of pancreatic fragments is introduced ("intestinalization") in which vascularized fragments are placed inside a jejunal pouch. This step is done to manage all secretions, lymph and potential debris coming from the pancreas; to maintain the primary portal drainage of insulin; to avoid vascular operations, and to keep the fragment in a denervated state and still preserve its endocrine function to prevent diabetes. The procedure was compared with conventional end to end pancreaticojejunostomy. Sixteen dogs were studied. Group 1 consisted of four dogs that had intestinalization of the pancreatic tail. Group 2 is made up of eight dogs that had complete resection of the remaining duodenal portion of the gland as well as intestinalization of the pancreatic tail. Group 3 consisted of four dogs that had end to end pancreaticojejunostomy to the isolated tail and complete resection of the duodenal portion of the gland as those dogs in group 2. No dog became diabetic during the time of observation (up to one year)--fasting glucose levels and K values in glucose tolerance tests remained normal. Insulin peak values at ten minutes were lower postoperatively. However, return to fasting levels occurred equally fast postoperatively. There was no difference among the groups. The most important morphologic finding in the intestinalized fragments was a firm capsule surrounding the tissue after two weeks. Exocrine atrophy was present in both groups 2 and 3 after one year. No reinnervation of intestinalized pancreas was seen. Intestinalization may offer an alternative to pancreatic resection especially when heterotopic autotransplantation is considered.

Amylases

The role of biliary obstruction in the pathogenesis of acute pancreatitis in the opossum.

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.

Acute Disease