Human Sphincter Research Articles

„Stone splinter“ like phasic contraction abnormality of the human sphincter of ODDI (SO) – a preliminary report of two cases documented by endoscopic so manometry

Introduction: Currently elevated SO basal pressure is the only accepted manometric abnormality in patients with postcholecystectomy pain and SO dysfunction (SOD) that necessitates therapeutic measures such as endoscopic sphincterotomy (EST). Although normal ranges of SO phasic contractions (PCs) are well described in healthy volunteers, no specific PC abnormalities were characterized in SOD patients.

Differing effects of pethidine and morphine on human sphincter of Oddi motility

The aim of this study was to evaluate the effects of morphine and pethidine on human sphincter of Oddi motility. The action of these opioids on the sphincter of Oddi was evaluated by means of intraoperative manometry in 36 patients undergoing elective cholecystectomy. Both opioids were given in intravenous cumulative equipotent doses up to a maximum of 10 micrograms/kg morphine or 100 micrograms/kg pethidine. At these doses, morphine increased the mean(s.d.) frequency of contractions from 2.4(1.0) to 7.9(1.6) (P less than 0.001); this effect was reduced by naloxone (0.04 mg bolus, P less than 0.05). Pethidine inhibited the frequency of contractions from 1.5(0.8) to 0.8(0.5) (P less than 0.05); this response was blocked by atropine (0.6 mg bolus, P less than 0.01). Pretreatment with atropine or naloxone reduced the frequency of contractions significantly (P less than 0.05). The results illustrate different responses to pethidine and morphine of the sphincter of Oddi, and provide a pharmacological explanation for the suitability of pethidine over morphine as the analgesic of choice in patients experiencing biliary pain.

Electrically evoked activity in the human external anal sphincter.

Following electrical stimulation of perianal skin, short latency evoked electromyographic (EMG) responses from the external and sphincter have been interpreted as the electrophysiological correlate of the anal reflex. Delayed responses in patients with idiopathic faecal incontinence have been interpreted as evidence for denervation of the external anal sphincter. Electrically evoked responses were studied in normal subjects, either before and during spinal anaesthesia (n = 8), or before and during competitive neuromuscular blockade (n = 4), instituted for operative purposes. Short latency responses persisted unchanged in either latency or duration during spinal anaesthesia whereas long latency responses were completely abolished. Both short and long latency responses were abolished during competitive neuromuscular blockade. Short latency responses are not spinal reflex in nature, but due to stimulus activation of alpha-motoneuronal terminal branches. Delayed responses in incontinent patients cannot be interpreted as evidence for pudendal neuropathy. Long latency (i.e. greater than 40 ms) responses demand a functional sacral spinal cord and represent the true anal reflex. Their wide range of latency in normal subjects suggests this measurement will be of little use in confirming the presence or absence of pudendal neuropathy, and that other measures of neuropathy may be more appropriate.

Human fasting and postprandial sphincter of Oddi motility.

Sphincter of Oddi motility was evaluated in post-cholecystectomy patients with indwelling T tubes during fasting and after feeding. A triple-lumen catheter was positioned to record from the sphincter of Oddi and duodenum. The sphincter of Oddi was characterized by phasic contractions independent of duodenal contractions. During fasting duodenal wave frequency exhibited four phases, whereas only two phases could be identified from the sphincter of Oddi. A prolonged phase A in the sphincter of Oddi corresponded to duodenal phases I, II and IV. A short phase B in the sphincter of Oddi just preceded the onset of duodenal phase III and was temporally related to it. Sphincter of Oddi basal pressure increased during duodenal phases III and IV. After ingestion of food, sphincter of Oddi basal pressure, wave amplitude and duration decreased, but the frequency remained unchanged. Conversely, duodenal frequency increased but there was no change in amplitude. Thus, the human sphincter of Oddi and duodenum exhibited independent motility demonstrating distinct phases during the interdigestive period. After food, sphincter of Oddi motility altered in a manner which would facilitate the passive flow of fluid into the duodenum.

Effects of different drugs on the sphincter of Oddi motility: study with choledochoscope manometry

This study assessed the effects of narcotic analgesics, nitrates drugs, somatostatin analogues on human sphincter of Oddi motility and the antagonistic effects of nitrates drugs and anticholinergic agents against morphine measured by choledochoscope manometry. 157 patients who had a T tube after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly divided into 5 groups. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. SOBP, SOCA and SOF increased after injection of morphine and Ap-237, CBDP increased after intramuscular administered morphine. No apparent change occurred after intramuscularly administered pethidine. SOBP and SOCA decreased after tramadol. After intravenous administration of stilamin in a dose of 250 microg/h, SOCA increased. After administration stilamin of 500 microg/h dose, SOCA and SOBP declined. After intravenous administration of sandostatin, CBDP increased obviously. BPOS and SOCA decreased significantly after administration of isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN), SOBP reduced evidently after application of pentaerythritol tetranitrate (PTN). SOBP, SOCA, SOF and CBDP increased evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased. As to associated application with PTN, SOCA and SOF decreased. After associated application of anisodamine or atropine, SOCA, SOBP declined, after injected buscopan, SOCA, SOBP, SOF all declined. The regular dose of morphine and Ap-237 shows excitatory effect on the sphincter of Oddi motility. Tramadol shows inhibitory effect on the sphincter of Oddi. The regular dose of pethidine and sandostatin shows no apparent effect on the sphincter of Oddi. Stilamin in low dose shows excitated effect on the sphincter of Oddi. Nitrates drugs show inhibited effects on SO motility. Nitrates drugs and anticholinergic agents can antagonize the excitated effect of morphine.

Nitroester drug’s effects and their antagonistic effects against morphine on human sphincter of Oddi motility

To evaluate the effects of nitroester drugs on human sphincter of Oddi (SO) motility and their antagonistic effects against morphine which shows excitatory effect on Oddi's sphincter motility. The effects of these drugs on SO were evaluated by means of choledochofiberoscopy manometry. A total of 67 patients having T-tubes after cholecystectomy and choledochotomy were involved in the study, they were randomly divided into glyceryl trinitrate (GTN) group, isosorbide dinitrate (ISDN) group, pentaerythritol tetranitrate (PTN) group, morphine associated with GTN group, morphine associated with ISDN group and morphine associated with PTN group. Basal pressure of Oddi's sphincter (BPOS), amplitude of phasic contractions (SOCA), frequency of phasic contractions (SOF), duration of phasic contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. Morphine was given intramuscularly while nitroester drugs were applied sublingually. BPOS and SOCA decreased significantly after administration of ISDN and GTN, BPOS reduced from 10.95+/-7.49 mmHg to 5.92+/-4.04 mmHg (P<0.05) evidently after application of PTN. BPOS increased from 7.37+/-5.58 mmHg to 16.60+/-13.87 mmHg, SOCA increased from 54.09+/-38.37 mmHg to 100.70+/-43.51 mmHg, SOF increased from 7.15+/-3.20 mmHg to 10.38+/-2.93 mmHg and CBDP increased 3.75+/-1.95 mmHg to 10.49+/-8.21 mmHg (P<0.01) evidently after injection of morphine. After associated application of ISDN and GTN, the four indications above decreased obviously. As for application associated with PTN, SOCA and SOF decreased separately from 100.64+/-44.99 mmHg to 66.17+/-35.88 mmHg and from 10.70+/-2.76 mmHg to 9.04+/-1.71 mmHg (P<0.05) markedly. The regular dose of GTN, ISDN and PTN showed inhibitory effect on SO motility, morphine showed excitatory effect on SO while GTN, ISDN and PTN could antagonize the effect of morphine. Among the three nitroester drugs, the effect of ISDN on SO was most significant.

Calcium channel antagonists and inhibition of human sphincter of Oddi contractions

Objective. Nifedipine has been used in the treatment of sphincter of Oddi dyskinesia, a biliary disease characterized by upper abdominal pains and increased pressure in the sphincter. The effects of other calcium channel antagonists on sphincter of Oddi have not been elucidated. Material and Methods. We compared the effects of three calcium blockers with differing smooth muscle selectivity (verapamil, nifedipine and felodipine) on human sphincter of Oddi contractions. Transverse sections of the sphincter obtained from five patients undergoing Whipple resection were studied in an organ bath chamber in vitro. Results. All three calcium blockers significantly (>50%) inhibited the acetylcholine-induced and KCl-induced sphincter contractions in a dose-dependent manner. Both nifedipine and felodipine were more potent than verapamil in inhibiting the acetylcholine-induced contractions, whereas only nifedipine, but not felodipine, reduced the KCl-elicited contractions more than verapamil. Conclusions. The smooth muscle selective calcium channel antagonists are potent inhibitors of human sphincter of Oddi contractions. Although nifedipine is, to date, the only agent studied in clinical settings, other dihydropyridines are also likely to be useful in sphincter of Oddi dyskinesia.

Outcome after implantation of a novel prosthetic anal sphincter in humans.

A novel prosthetic anal sphincter (PAS) has been developed that aims to occlude by flattening and angulating the bowel, reproducing the action of the puborectalis muscle. The safety of the PAS has been confirmed in biomechanical, in vitro and long-term animal survival studies. The Medical Devices Agency approved implantation in 12 patients. The PAS was placed in the pelvis around the anorectal junction via a transabdominal approach in 12 patients with severe faecal incontinence. The device was activated 6 weeks after surgery. Fibreoptic examination of the mucosa below the device was undertaken at various intervals during review. At a median follow-up of 59 (range 30-72) months nine of the 12 patients had a functioning PAS. There were no device-related infective complications after the initial operation but one patient developed pseudomembranous colitis and had the device removed. The PAS was effective in restoring continence in ten of 11 patients. Median (range) Cleveland Clinic continence scores improved from 16 (7-20) before to 3 (0-7) after surgery. In two patients the PAS was eventually removed owing to infection after revisional surgery. There was no clinical or histological evidence of gastrointestinal mucosal ischaemia. The PAS was effective in restoring continence. There was no device-related infection after the initial operation, no device erosion and no clinical or histological evidence of gastrointestinal ischaemia.

Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility.

Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.

Human rhabdosphincter cell culture: a model for videomicroscopy of cell contractions.

Physiology of the human rhabdosphincter and its innervation are still a subject to controversy. A better understanding of rhabdosphincter function and anatomy might help to solve important urological problems like urinary incontinence. It was the aim of the present study to develop a human sphincter cell culture model for investigation of contraction mechanisms in vitro. METHODS AND RESULTS Cells were isolated from human rhabdosphincter tissue obtained from prostatectomy and cystoprostatectomy specimens. Cultured cells expressed typical features of striated muscle cells. By means of videomicroscopy with a time lapse videosystem cell contractions could be documented. Under control conditions without any contractile stimulant 8% of the cells were seen to contract. Cholinergic stimulation with 10 mM of acetylcholine induced a significant increase in contraction rate to 49%. These results demonstrate that cholinergic stimulation triggers contraction of cultured human rhabdosphincter cells. This model might help to understand external urethral sphincter physiology and to establish new therapies for the treatment of sphincter dysfunctions. Prostate 47:189-193, 2001.

The development of the external urethral sphincter in humans.

To assess the hypothesis that during fetal development, the external urethral sphincter changes from a concentric sphincter of undifferentiated muscle fibres to a transient ring of striated muscle which regresses caudo-cranially in the posterior urethra during the first year of life, when the sphincter assumes its omega-shaped configuration. The anatomy and development of the external urinary sphincter was assessed in human males and females during fetal life. Plastic-embedded sections (transverse, sagittal and frontal planes; 300-700 microm) of the pelvis of 31 females and 31 males (9 weeks of gestation to newborn) were stained with azure II/methylene blue/basic fuchsin and viewed at x 4-80. The sections of interest were taken from the bladder neck to the perineum. The sections of the membranous urethra were reconstructed three-dimensionally using a computer program. In both male and female an omega-shaped external sphincter was apparent in all specimens at > 10 weeks of gestation. In the early fetal period (ninth week), there was undifferentiated mesenchyme; in this period the mesenchyme was more dense in the anterior part and loose in the posterior part of the urethra. In females, there was a close connection between the urethra and the anterior wall of the vagina. The omega-shaped configuration of the external urethral sphincter was recognisable from 10 weeks of gestation in both sexes. There was no suggestion of a change from a cylindrical to an omega-shaped sphincter in the fetal period to birth. Also, a transient 'tail' posterior to the sphincter was not apparent. The rectovesical septum was well developed in neonates. There is no reason to assume that the development of the septum leads to an apoptosis of muscle cells in the posterior part of the external sphincter in males after birth. The anatomical development of the external sphincter does not explain transient outlet obstruction during fetal life. The function of the muscle may change during development because of neuronal maturation.

Prostaglandin F2α(PGF2α)-induced contraction of human esophageal and lower esophageal sphincter circular smooth muscle

Prostaglandin F2α(PGF2α)-induced contraction of human esophageal and lower esophageal sphincter circular smooth muscle

Prostaglandin F2α(PGF2α)-induced contraction of human esophageal and lower esophageal sphincter circular smooth muscle

Prostaglandin F2α(PGF2α)-induced contraction of human esophageal and lower esophageal sphincter circular smooth muscle

Effects of cisapride on smooth muscle activities of oesophagus and lower oesophageal sphincter in humans

Effects of cisapride on smooth muscle activities of oesophagus and lower oesophageal sphincter in humans

Calcium regulation in the human lower esophageal sphincter

Calcium regulation in the human lower esophageal sphincter

Effects of acid perfusion on the human lower esophageal sphincter (LES) and esophageal contractions

Effects of acid perfusion on the human lower esophageal sphincter (LES) and esophageal contractions

Vector assayof the human sphincter of Oddi(SO) by endoscopic biliary manometry

Vector assayof the human sphincter of Oddi(SO) by endoscopic biliary manometry

Electroacupuncture may relax the contraction of human sphincter of Oddi via the cholecystokinin release

Electroacupuncture may relax the contraction of human sphincter of Oddi via the cholecystokinin release

6998 Effects of synthetic prostaglandins e1 and f2a on motility of the sphincter of oddi in humans.

Background/Aim: Prostaglandins (PGs), widely distributed in the human and animal gastrointestinal tract, play important roles in cytoprotection, secretion and absorbtion, and motility of the digestive tract. However, their effects on the biliary tract are not well studied. The aim of the present study is to investigate effects of PGs E1 and F2a on motility of the human sphincter of Oddi (SO). Methods: Twenty-seven patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), alprostadil alfadex, a synthetic PGE1 analogue, at a dose of either 0.05 or 0.1 μg/kg/min (seven patients for each condition), or dinoprost, a synthetic PGF2α analogue, at a dose of 1.0 μg/kg/min (seven patients). Endoscopic biliary manometry was done with a recording of basal SO pressure (mmHg), SO phasic wave amplitude (mmHg) and frequency (/min) before and 5 min after intravenous infusions, using a 4 Fr microtransducer catheter (Galtec Ltd). Values are reported as the mean±SEM. Paired Student's t tests were used to compare variables before and after injection. Differences with p values of less than 0.05 were considered significant. Results: There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure and SO phasic wave frequency at a dose of 0.05 μg/kg/min and significantly decreased all parameters at a dose of 0.1 μg/kg/min, while dinoprost significantly increased only SO phasic wave frequency. Conclusion: A synthetic PGE1 analogue, alprostadil alfadex, has an inhibitory effect on motility of the human SO.This drug may be applicable to clinical use as a SO relaxing agent.

The effects of somatostatin and octreotide on the human sphincter of Oddi.

Somatostatin acts at different sites in the human gastrointestinal tract and generally inhibits the release and effects of many gastrointestinal hormones and neuropeptides. Together with its long-acting analogue octreotide, somatostatin is widely used in the treatment of hormone-producing tumours, variceal bleeding, etc., but multi-centre trials have failed to prove a beneficial effect in the treatment of acute pancreatitis or in the prevention of post-ERCP pancreatitis (pancreatitis following endoscopic retrograde cholangiopancreatography). The aim of the present work was to study the effects of somatostatin and octreotide on the human sphincter of Oddi by means of quantitative hepatobiliary scintigraphy (QHBS). Fifteen cholecystectomized patients were enrolled in the study, six in the somatostatin group and nine in the octreotide group. QHBS was performed initially with a standard protocol (baseline data), then repeated after 0.1 mg octreotide or a 250 microg bolus + 250 microg/h somatostatin administration. In the 60th min of QHBS, 0.5 mg glyceryl trinitrate (GTN) was administered sublingually. QHBS demonstrated that both somatostatin and octreotide caused a marked impairment in the bile flow: the half-time of excretion (T1/2) over the common bile duct was significantly prolonged compared with baseline data (somatostatin group: common bile duct T1/2 180 min versus 59.7+/-31 min; octreotide group: common bile duct T1/2 140.9+/-60.5 min versus 30.7+/-11.7 min). Glyceryl trinitrate administration accelerated the transpapillary bile flow, with significant decreases in the elevated T1/2 in both groups. Increased transpapillary flow induced by glyceryl trinitrate may be beneficial in the treatment of acute or post-ERCP pancreatitis.