Electrical activation of common bile duct nerves modulates sphincter of Oddi motility in the Australian possum.

BACKGROUND: Sphincter of Oddi (SO) motility is regulated by extrinsic and intrinsic nerves. The existence of neural circuits between the SO and the proximal extrahepatic biliary tree has been reported, but they are poorly understood. Using electrical field stimulation (EFS), we determined if a neural circuit exists between the common bile duct (CBD) and the SO in anaesthetized Australian brush-tailed possums. METHODS: The gallbladder, cystic duct or CBD were subjected to EFS with a stimulating electrode. Spontaneous SO phasic waves were measured by manometry. RESULTS: EFS at sites on the distal CBD (12-20 mm proximal to the SO), but less commonly at more proximal CBD, evoked a variety of responses consisting of an excitatory and/or inhibitory phase. Bi-phasic responses consisting of an excitation followed by inhibition were the most common. Tri-phasic responses were also observed as well as excitation or inhibition only. These evoked responses were blocked by topical application of local anaesthetic to the distal CBD or transection of the CBD. EFS at sites on the gallbladder body, neck or cystic duct did not consistently evoke an SO response. Pretreatment with atropine or guanethidine reduced the magnitude of the evoked response by about 50% (p<0.05), pretreatment with hexamethonium had no consistent effect and pretreatment with a nitric oxide synthase inhibitor increased the response. DISCUSSION: A neural circuit(s) between the SO and the distal CBD modulates SO motility. Damage to this area of the CBD during bile duct exploration surgery could adversely affect SO motility.

Oropharyngeal scintigraphy: a reliable technique for the quantitative evaluation of oral-pharyngeal swallowing.

A valid and reliable technique to quantify the efficiency of the oral-pharyngeal phase of swallowing is needed to measure objectively the severity of dysphagia and longitudinal changes in swallowing in response to intervention. The objective of this study was to develop and validate a scintigraphic technique to quantify the efficiency of bolus clearance during the oral-pharyngeal swallow and assess its diagnostic accuracy. To accomplish this, postswallow oral and pharyngeal counts of residual for technetium-labeled 5- and 10-ml water boluses and regional transit times were measured in 3 separate healthy control groups and in a group of patients with proven oral-pharyngeal dysphagia. Repeat measures were obtained in one group of aged (> 55yr) controls to establish test-retest reliability. Scintigraphic transit measures were validated by comparison with radiographic temporal measures. Scintigraphic measures in those with proven dysphagia were compared with radiographic classification of oral vs. pharyngeal dysfunction to establish their diagnostic accuracy. We found that oral ( p = 0.04), but not pharyngeal, isotope clearance is swallowed bolus-dependently. Scintigraphic transit times do not differ from times derived radiographically. All scintigraphic measures have extremely good test-retest reliability. The mean difference between test and retest for oral residual was -1% (95% CI -3%-1%) and for pharyngeal residual it was -2% (95% CI -5%-1%). Scintigraphic transit times have very poor diagnostic accuracy for regional dysfunction. Abnormal oral and pharyngeal residuals have positive predictive values of 100% and 92%, respectively, for regional dysfunction. We conclude that oral-pharyngeal scintigraphic clearance is highly reliable, bolus volume-dependent, and has a high predictive value for regional dysfunction. It may prove useful in assessment of dysphagia severity and longitudinal change.

Induction of duodenal motility activates the sphincter of Oddi (SO)-duodenal reflex in the Australian possum in vitro.

1 The aim of this study was to determine if stimulation of duodenal motility by duodenal fluid distension or by administration of carbachol, activates the sphincter of Oddi-duodenal reflex, in an in vitro preparation from the Australian possum. 2 Duodenal distension was achieved by infusion of Krebs solution (0-8 cm H2O). In separate experiments, the sphincter of Oddi (SO) was partitioned from the duodenum and carbachol (10(-7) - 5 x 10(-6) M) added to the duodenal compartment. 3 Fluid distension increased duodenal motility to 120-600% of control activity. These treatments induced increased SO motility (to 120-390% of control) in six preparations, reduced activity (to 60% of control) in one and no response in another. 4 Addition of carbachol to the duodenal compartment resulted in increased duodenal motility. SO motility was increased in seven preparations, reduced in another two and no response were evoked in two others. All SO responses were blocked by tetrodotoxin pretreatment. 5 These data suggest that the SO receives inputs from duodenal mechano and/or stretch receptors resulting in excitatory or inhibitory responses, with the excitatory response dominating. These findings support the role for the SO-duodenal reflex in preventing duodenobiliary/pancreatic reflux during periods of elevated duodenal activity.

Distribution of nitric oxide synthase and vasoactive intestinal polypeptide immunoreactivity in the sphincter of Oddi and duodenum of the possum.

The nitrergic innervation of the sphincter of Oddi (SO) and duodenum in the Australian brush-tailed possum and the possible association of this innervation with the neuropeptide vasoactive intestinal polypeptide (VIP) were investigated by using immunohistochemical localisation of nitric oxide synthase (NOS) and VIP, together with the general neuronal marker, protein gene product 9.5 (PGP9.5). Whole-mount preparations of the duodenum and attached SO without the mucosa, submucosa and circular muscle (n=12) were double- and triple-labelled. The density of myenteric nerve cell bodies of the SO in the more distal region (duodenal end) was significantly higher than that in the more proximal region. In the SO, approximately 50% of all cells were NOS-immunoreactive (IR), with 27% of the NOS-IR cells being VIP-IR. Within the duodenal myenteric plexus, NOS immunoreactivity was present in about 25% of all neurons, with 27% of these NOS-IR neurons also being VIP-IR, a similar proportion to that in the SO. Varicose nerve fibres with NOS and VIP immunoreactivity were present within the myenteric and submucous plexuses of the SO and duodenum, and in the circular and longitudinal muscle layers. The NOS-positive cells within both the SO and duodenum were unipolar, displaying a typical Dogiel type I morphology. The myenteric plexuses of the SO and duodenum were in direct continuity, with many interconnecting nerve trunks, some of which showed NOS and VIP immunoreactivity. Thus, the possum possesses an extensive NOS innervation of the SO and duodenum, with a significantly higher proportion of NOS-IR neurons within the SO, a subset of which contains VIP.

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.

Somatostatin stimulates the brush-tailed possum sphincter of Oddi in vitro and in vivo.

BACKGROUND & AIMS: Somatostatin, a neuropeptide and hormone, is found in the biliary tract of several species. The aim of this study was to map the distribution of somatostatin-like immunoreactive nerve fibers in the extrahepatic biliary tract of the Australian possum and to determine the pharmacological effects of somatostatin 1-14 on sphincter of Oddi activity in vitro and in vivo. METHODS: Tissue was harvested for immunohistochemistry and sphincter of Oddi for circular or longitudinal muscle contractility. In anesthetized possums, sphincter of Oddi motility was measured by manometry, and transsphincteric flow was measured gravimetrically. RESULTS: Somatostatin immunoreactivity was evident in gallbladder ganglia nerve cell bodies and in nerve fibers of the common bile duct and sphincter of Oddi. Somatostatin 1-14 increased circular and longitudinal muscle contraction amplitude 3-4-fold (P < 0.05), but only the longitudinal muscle contraction amplitude was tetrodotoxin sensitive. Somatostatin 1-14 stimulated spontaneous sphincter of Oddi motility in a tetrodotoxin-insensitive manner, increasing basal pressure, contraction frequency, and amplitude 2-4-fold (P < 0.05) and reducing transsphincteric flow to 25% of control (P < 0.0001). CONCLUSIONS: Somatostatin-like immunoreactivity is present in the extrahepatic biliary tree, and somatostatin 1-14 stimulates sphincter of Oddi smooth muscle and nerves. The major action is direct stimulation of sphincter of Oddi circular muscle, which reduces transsphincteric flow.

In vitro characterisation of intramural neural pathways between the duodenum and the sphincter of Oddi of the brush-tailed possum.

The aims of this study were to determine if neural pathways between the duodenum and sphincter of Oddi are intramural, activated by duodenal electrical field stimulation (EFS) in vitro, and contain capsaicin-sensitive primary afferents. The possible involvement of cholinergic (muscarinic and/or nicotinic) and adrenergic receptors in these pathways were also investigated. Duodenal EFS (5-60 Hz, 70 V, 0.5 ms duration, 10 s train) at sites 2 cm oral and 2 cm anal to the sphincter of Oddi-duodenal junction produced frequency-dependent excitatory responses in the sphincter of Oddi, measured by manometry (n = 3). Excitatory responses from duodenal circular muscle were also evident. Tetrodotoxin (1 microM; n = 7) pretreatment abolished both sphincter of Oddi and duodenal responses to duodenal EFS. Crushing the duodenum between the site of stimulation and the sphincter of Oddi-duodenal junction also abolished sphincter of Oddi response. The sphincter of Oddi responses to duodenal EFS at the oral and anal sites were reduced by pretreatment with (i) atropine (100 nM: n = 7) to 19 +/- 6% (P < 0.05) and 22 +/- 8% (P < 0.05) of control respectively. (ii) hexamethonium (100 microM: n = 9) to 10 +/- 2% (P < 0.01) and 6.0 + 2.5% (P < 0.01) of control respectively and (iii) guanethidine (1 microM; n = 6) to 75 +/- 6% (P < 0.05) and 78 +/- 10% (P < 0.05) of control, respectively. Combined pretreatment with phentolamine and propranolol (both 1 microM; n = 7) was without effect, as was capsaicin (1 microM; n = 12) pretreatment. Excitatory intramural pathways between the sphincter of Oddi and the duodenum are primarily cholinergic in nature and contain an adrenergic component. Capsaicin-sensitive primary afferents are not involved.

Influence of surgery on deglutitive upper oesophageal sphincter mechanics in Zenker's diverticulum.

BACKGROUND/AIMS: To evaluate the role of upper oesophageal sphincter (UOS) compliance in dysphagia, the functional consequences of surgery were evaluated in eight patients with pharyngeal diverticula. The study examined the hypotheses that hypopharyngeal intrabolus pressure is an indicator of UOS compliance and that UOS opening and intrabolus pressure are normalised by surgery. METHODS: In eight patients and nine healthy controls, we measured the timing of swallow events, UOS relaxation, maximal UOS dimensions, intrabolus pressure, and trans-sphincteric bolus flow rates by simultaneous videoradiography and pharyngeal manometry. RESULTS: Bolus flow rates were not changed by surgery. Surgery significantly increased UOS opening (p = 0.0001) and reduced hypopharyngeal intrabolus pressure (p = 0.0001). The slope of the relation between sphincter area and intrabolus pressure was steeper in patients than controls and was normalised by surgery. Surgery had minor effects on basal UOS tone and timing of swallow events. CONCLUSIONS: Upper oesophageal sphincter compliance is poor in Zenker's diverticulum and is normalised by surgery. Hypopharyngeal intrabolus pressure, which correlates with resistance to trans-sphincteric bolus flow, is a useful indicator of UOS compliance. Intrabolus pressure may be a predictor of outcome after myotomy in pharyngeal dysphagia. Cricopharyngeal myotomy is a mandatory component of surgery for Zenker's diverticulum.

Trigeminal motoneuron responses to vestibular stimulation in the guinea pig.

Experiments performed in the guinea pig were aimed at evaluating the effect of electric or caloric stimulations of the vestibular afferents on the electrical activity of the jaw-closing and jaw-opening trigeminal motoneurons. Results showed that masseter and digastric motoneurons mainly responded to vestibular ampullar activation with excitatory responses, with latencies being shorter for contralateral than ipsilateral ampullar stimulation. Differences in latencies between the jaw-closing and jaw-opening trigeminal motoneurons were observed: the masseter motoneurons constantly responded about 2 msec earlier than the digastric motoneurons. These results suggest that the vestibular-trigeminal relationship is quite complex and uses multiple systems to connect the vestibular apparatus with the trigeminal motor nuclei. From the functional point of view, the vestibular-trigeminal relationship may play a role in the dynamic control of the jaw muscle tone during head movements.

Influence of normal aging on oral-pharyngeal and upper esophageal sphincter function during swallowing.

The influence of aging on oral-pharyngeal swallowing was assessed by simultaneous manometry and videoradiography in 14 nondysphagic elderly individuals (mean age 76 yr) and 11 healthy, young controls (mean age 21 yr). Sphincter opening was diminished significantly in the elderly (P = 0.0001), but trans-sphincteric bolus flow rates were preserved. The increased impedance to trans-sphincteric bolus flow from reduced sphincter opening in the aged was reflected in a significant increase in hypopharyngeal intrabolus pressure (P = 0.003). Oral transit time was significantly prolonged in the aged (P = 0.01). The timing of upper esophageal sphincter (UES) manometric relaxation and of opening was significantly delayed in the aged (P = 0.0001), and this delay was comparable in magnitude to the prolongation in oral transit. Coordination of UES relaxation and opening with midpharyngeal contraction was not significantly affected by age. Deglutitive hyolaryngeal motion was not affected by age but was delayed by a duration equivalent to the prolongation in oral transit. We conclude that normal aging prolongs the oral-pharyngeal swallow that impairs UES opening but does not influence pharyngo-sphincteric coordination.

Effect of fetal hypoxia on seizure susceptibility in rats.

In the present study, susceptibility to Pentylentetrazol (PTZ)-induced seizures was tested in 45 four-wk old rats born to mothers exposed to moderate asphyxia in the last week of pregnancy by breathing N2 99.9% for 6 min in two separate sessions, (Group I--experimental rats) and in 44 rats of the same age, born after a normal pregnancy (Group II--controls). The results showed that the experimental rats, following episodes of asphyxia in intrauterine life, had a higher susceptibility to PTZ-induced seizures than the controls, manifested by earlier onset of convulsions and a higher incidence of fetal epileptic status. This occurred despite normal development and the absence of neurological deficits in the experimental rats in the first 4 wk of extrauterine life.

Vestibular and somatosensory afferents modulate masseter muscle activity.

The aim of the research was to investigate whether somatosensory impulses starting from the forelimbs could modulate masseter muscle activity in anesthetized guinea pigs. The effect of interactions between radial nerve and vestibular stimulations on the masseter motor unit responses was also studied. Results show that electrical stimulation of both radial nerves induces responses in the masseter motor units most frequently characterized by excitation at latency ranging from 14 to 29 ms. The radial nerve responses were strongly reduced by conditioning electrical stimulation of the vestibular ampullar receptors. Similarly, the vestibular responses were reduced by conditioning radial nerve stimulation. The natural activation of the vestibular macular receptors can either decrease or increase the masseter motor unit responses evoked by electrical stimulation of the radial nerve. These complex inhibitory-excitatory interactions between the two sensory inputs could control the masseter postural tone in relation to the head and limb positions in space.

Hypoglossal responses elicited by periodontal afferent activation in the rat.

Mechanical stimulation of the ipsilateral incisor tooth in the rat evoked reflex discharges in the hypoglossal nerve branch innervating the intrinsic and extrinsic tongue muscles. Stimulation elicited biphasic potentials in the whole XIIth nerve and influenced the unitary firing rate in 54 out of 80 fibers tested. The fiber responses were characterized by excitation or inhibition in frequency discharge or sequences of excitation-inhibition or inhibition-excitation. The results observed suggest that the periodontal-hypoglossal reflexes play a role in the control of tongue position during mastication.

Muscle spindle and periodontal trigeminal afferents modulate the hypoglossal motoneuronal activity.

Hypoglossal responses to electrical or natural activation of the afferent fibers of the masseteric nerve and to periodontal mechanoreceptors were recorded in rats. Electrical stimulation of the masseteric nerve, at an intensity adequate to excite prevalently the primary spindle afferents, induced various sequences of excitation-inhibition and inhibition-excitation in 55% of the tested hypoglossal motoneurons. Responses were characterized by excitation, inhibition or excitation-inhibition sequences occurring at short and long latencies. Different pattern of responses were evoked in both the protrusive and the retractive motoneurons of the homolateral hypoglossal nucleus. Moreover, jaw lowering and pressure on the incisor tooth induced antagonistic and synergistic effects on the electrical activity of the same hypoglossal motoneurons. The results show for the first time that afferent signals from both muscle spindles and periodontal receptors modulate the activity of the hypoglossal motoneurons aimed at controlling the tongue position in the mouth during mastication.

Masseter muscle responses to forelimb nerve stimulation in the guinea pig.

These experiments were aimed at clarifying the spinal-masseteric connections by observing the effect of electrical stimulation of radial nerve afferents on masseter muscle activity. Spontaneous and evoked electrical responses of the masseter motor units were recorded with tungsten microelectrodes and analysed on computer. Results show that electrical stimulation of both radial nerves induces responses in single masseter motor units. The response patterns were characterized most frequently by excitation, but also by a sequence of excitation inhibition. The latency in masseter muscle responses were found to be lower in contralateral recordings: 18.26 +/- 4.04 msec (x +/- SD) compared with a latency of 24.3 +/- 5.25 msec in ipsilateral recordings. These observations confirm the hypothesis that somatosensory impulses eminating from the radial nerve participate in the postural control of the masseter muscle aimed at maintaining correct jaw position during forelimb displacement.