G. T. P. Saccone

Sphincter of Oddi dysfunction associated with choledochal cyst

Abstract The pathophysiology of choledochal cysts remains unclear, although an association with anomalous pancreato‐biliary junction and the reflux of pancreatic enzymes into the biliary tree is known. Sphincter of Oddi (SO) manometry was performed in three patients with choledochal cysts. All patients exhibited an elevated basal pressure diagnostic of sphincter of Oddi dysfunction. Two patients exhibited anomalous pancreato‐biliary junction. This report suggests an association between the choledochal cyst and sphincter of Oddi dysfunction, and may suggest that SO dysfunction plays a role in choledochal cyst formation.

Proximal and Distal Segments of the Possum Sphincter of Oddi Respond Differently to Neural and Cholecystokinin Octapeptide Stimulation in vitro

Background/Aims: Previous studies have demonstrated separate pancreatic duct (PD) and bile duct (BD) components of the sphincter of Oddi (SO) and suggested distinct proximal and distal functional segments. This study was designed to determine if proximal and distal segments of the BD component of the SO (BD-SO) and PD component of the SO (PD-SO) responded equally to (1) activation of SO-duodenal neural pathways, and (2) exogenous cholecystokinin octapeptide (CCK-8). Methods: Intact SO-duodenum preparations from Australian brush-tailed possums (n = 6) were mounted in organ baths. SO activity was recorded from the proximal and distal segments of BD-SO and PD-SO ± electrical activation of duodenal nerves at two separate sites. Full thickness muscle strips from the proximal and distal segments of the BD-SO and PD-SO were prepared (n = 8), mounted in organ baths, and exposed to CCK-8 (10–9– 10–6 M), ± tetrodotoxin. Results: Activation of duodenal nerves evoked different responses in some segments of the BD-SO and PD-SO, depending on the site of duodenal electrical stimulation. CCK-8 induced a concentration-dependent, tetrodotoxin-insensitive decrease in the contraction amplitude of SO muscle strips from the proximal but not the distal SO. BD-SO and PD-SO strips were not different. Conclusions: The SO is composed of BD and PD components each of which contains proximal and distal segments that can respond independently to appropriate stimuli.

Secretin induces variable inhibition of motility in different parts of the Australian possum sphincter of Oddi

The sphincter of Oddi (SO) may not function as a single structure. We aimed to determine the response of the proximal and distal segments of the bile duct (BD‐SO) and pancreatic duct (PD‐SO) components of the SO to secretin, with and without neural blockade with tetrodotoxin (TTX). In anaesthetized Australian possums, separate manometry catheters were placed in the proximal and distal BD‐SO or PD‐SO segments to record motility. Secretin, 50–1000 ng kg–1, was administered, followed by TTX, and re‐administration of secretin, 500 and 1000 ng kg–1. Changes in the motility index (MI, frequency × mean amplitude) were determined. Statistical analysis utilized repeated‐measures ANOVA. Secretin produced a dose‐dependent decrease in MI from the proximal and distal BD‐SO and PD‐SO (all P < 0.001). The maximum inhibition, at 1000 ng kg–1, was 21 ± 4%, 33 ± 6% and 42 ± 5% of control (mean ± SEM), for proximal and distal BD‐SO, and distal PD‐SO, respectively. The proximal PD‐SO MI, however, was inhibited to 62 ± 6% of control, at 1000 ng kg–1. TTX enhanced the secretin‐induced response to the same level at the four sites (P < 0.02). We conclude that secretin inhibits the motility of the possum SO in a nonuniform manner and is modulated by neural activity.

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action ofgastrin-releasing peptide in the extrahepatic biliarytree of the Australian brush-tailed possum wasinvestigated. Immunohistochemical staining of fixedspecimens demonstrated gastrin-releasing peptide-containing nervesthroughout the neural plexuses of the gallbladder,sphincter of Oddi, and mucosa of the common bile duct.Gastrin-releasing peptide (5-2000 ng/kg) increasedgallbladder tone to a level equivalent to that produced bycholecystokinin octapeptide (160 ng/kg). This action wastetrodotoxininsensitive. Sphincter of Oddi motility andtranssphincteric flow were not altered. Possible mediation of the gallbladder response bygastrin was examined. Gastrin (50-2500 ng/kg) stimulatedgastric acid secretion, elevated gallbladder motility to64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility.In conclusion, gastrinreleasing peptide-containingnerves are found in the neural plexus of the possumextrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by adirect action on gallbladder smooth muscle and also viarelease of gastrin.

Endogenous endothelin increases gallbladder tone and leads to acute cholecystitis in the Australian possum

Abstract  Endothelins are bioactive peptides produced by gallbladder epithelial cells. We aimed to determine the role of endothelins in acute cholecystitis. Escherichia coli lipopolysaccharide vs saline (sham) was instilled into the gallbladder lumen of Australian possums. Some animals received the non‐selective endothelin antagonist, tezosentan. At 4 or 24 h, plasma and gallbladder endothelins and white blood cell count (WBCC) were determined. Acute cholecystitis was assessed using a histopathology score. In other animals gallbladder tone was determined. At 4h, a dose‐dependent 60‐fold increase in gallbladder endothelin level occurred (P = 0.001) but other parameters remained comparable with sham animals. Epithelial cells were endothelin‐immunoreactive. At 24 h, the WBCC rose (P < 0.007), and severe cholecystitis developed. Gallbladder but not plasma endothelin levels remained elevated. Tezosentan pre‐treatment resulted in a histologically normal gallbladder, but the WBCC and gallbladder endothelin levels were elevated. Lipopolysaccharide or saline instillation also caused a time‐dependent increase in gallbladder tone over 4 h (P < 0.001), but not in control animals. This increase was reduced by tezosentan treatment. Gallbladder endothelin production is an early event in acute cholecystitis, increases gallbladder tone and plays a crucial role in the inflammatory process.

Effects of Acute Pancreatic Duct Obstruction on Pancreatic Perfusion: Implication of Acute Pancreatic Duct Decompression

Background: Acute pancreatitis can result in pancreatic ischaemia and necrosis. Pancreatic duct (PD) obstruction may be the first step causing ischaemia in acute pancreatitis. Nitric oxide donors can attenuate acute pancreatitis through improvement in compromised pancreatic perfusion (PP). In this study, we determined if (1) PD obstruction altered PP and (2) PD decompression or L-arginine administration reversed this change. Methods: Fifteen Australian possums were randomly assigned to two groups: Animals in group A ( n = 6) were subjected to 30 min of PD obstruction and 60 min of PD decompression. Animals in group B ( n = 9) were subjected to 120 min PD ligation and 60 min PD decompression. A subset group B ( n = 6) were subjected to intravenous L-arginine (100 μg/kg) at the end of 120 min of ligation and at the end of PD decompression. The PP (Laser Doppler fluxmetry), PD pressure and blood pressure were continuously monitored. Results: PD pressure increased from 2.9 ± 2.5 to 18.1 ± 4.9 mmHg following PD ligation. PP was reduced to 67.1% ± 4.5% ( P < 0.01) and 46.2% ± 7.5% ( P < 0.001) of baseline following 30 and 120 min of PD ligation, respectively. Following 60 min of PD decompression, PP was restored to 89.1% ± 13.4% ( P < 0.02) of the baseline in the 30-min group. However, following 120 min PD ligation, PP remained depressed. L-arginine administration after 120 min of PD ligation transiently increased PP from 46.2% ± 7.5% to 81.1% ± 8.6% ( P < 0.03) of baseline. This effect was reproduced if L-arginine was administered at the end of decompression ( P < 0.05). Conclusion: In patients with acute pancreatitis due to obstructive causes, early decompression of the PD may prevent early pancreatic ischaemia.

Relative Effects of Dihydropyridine L-Type Calcium Channel Antagonism on Biliary, Duodenal, and Vascular Tissues: An In Vivo and In Vitro Analysis in Australian Brush-Tailed Possum

Nifedipine is used to treat sphincter of Oddi dysfunction. Its effects on the biliary system and duodenum in relation to its known vascular actions are unclear. Our aims were to determine the relative tissue sensitivities to dihydropyridine L-type calcium channel antagonism in the sphincter of Oddi, gallbladder, duodenum, and vasculature. For in vivo studies, 23 possums received nifedipine at three different doses with blood pressure and sphincter of Oddi manometry recordings. For in vitro studies, tissues from 28 possums were pretreated with nicardipine (10−8–10−5 M) and cumulative concentrations of agonist were administered (carbachol, norepinephrine at 10−9–10−5 M). In in vivo studies, blood pressure fell significantly at a lower dose than sphincter of Oddi motility. In in vitro studies, the sphincter of Oddi was more sensitive than arterial tissue, with the duodenum especially sensitive. In conclusion, in the possum we found that L-type channel antagonism in vivo was more potent to the vasculature than the sphincter of Oddi but this was not confirmed in vitro.

Development of a sleeve sensor for measurement of sphincter of oddi motility

BACKGROUND AND STUDY AIMS Unavoidable catheter movement during sphincter of Oddi (SO) manometry can produce considerable variations in the basal pressure, due to movement of the recording sidehole. The sleeve sensor is a perfused channel which records the highest pressure point along its length. The aim of the study was to develop and evaluate a prototype sleeve sensor for SO manometry. MATERIALS AND METHODS Bench-testing was used to assess the dynamic performance of the sleeve and sidehole assemblies. Recordings were initially made with a standard triple-lumen catheter and then with a purpose-built manometric assembly which had a 15 mm long sleeve sensor. RESULTS A perfusion rate of 0.04 ml/min gave the best balance between baseline pressure offset and rise rate. Recordings were attempted in nine patients and successfully achieved in four. The sleeve and sidehole recordings of the maximal basal pressure did not differ significantly (mean +/- SEM, 86.1 +/- 26.5 mmHg vs. 90.1 +/- 21.0 mmHg, P = 0.57, r = 0.998). CONCLUSIONS Unnecessarily high perfusion rates are being used for SO manometry. The sleeve sensor has the potential to monitor SO pressure more reliably than the currently used perfused sidehole method and should enhance the safety of prolonged SO manometry.