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Motor function of gastric antrum and pylorus for evacuation of low and high viscosity meals in dogs.

In five conscious dogs motility of the antrum, pyloric sphincter, and duodenum was recorded with strain gauge transducers and induction coils. Gastric evacuation of low, medium, and high viscosity meals was measured via a duodenal cannula and observed simultaneously by radiography. Computer analysis of the propagation of the gastric waves revealed increased velocity in the distal antrum but no simultaneous contractions of the terminal antrum and pyloric sphincter. Radiography showed, and measurements of the antral diameter confirmed, that the indentations of the gastric waves were significantly deeper with the low viscosity liquid meal compared with the medium and high viscosity meals. Thereby, retropulsion of the medium and high viscosity ingesta was produced. Results indicated that gastric evacuation was regulated predominantly by the depth of the peristaltic indentation, which depended on the viscosity of the gastric contents. Nothing indicated that the phasic contractions of the pyloric sphincter were of importance for the regulation of gastric emptying.

Animals↗

4-aminopyridine restores visual ocular motor function in upbeat nystagmus.

The effect of the potassium channel blocker 4-aminopyridine (4-AP) on spontaneous upbeat nystagmus (UBN) was investigated with the search coil technique during fixation in different gaze positions and smooth pursuit in a patient before and after ingestion of 10 mg 4-AP. UBN was reduced from 8.6 deg/s to 2.0 deg/s by 4-AP causing subjective relief from distressing oscillopsia, and impaired upward smooth pursuit was restored (gains: before medication 0.38; after medication 0.86). In the dark, UBN was slightly stronger and not affected by 4-AP. We propose that 4-AP improved the function of cerebellar pathways that mediate gaze holding and smooth pursuit by intensifying the excitability of cerebellar Purkinje cells.

4-Aminopyridine↗

Mechanisms underlying recovery of motor function after stroke.

Neurological damage, and stroke in particular, is the leading cause of long term disability worldwide. There is growing interest in the part that central nervous system reorganisation plays in recovery of function. Techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation permit the non-invasive study of the working human brain, and suggest that functionally relevant adaptive changes occur in the human brain after focal damage. An understanding of how these changes are related to recovery will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and that are designed to minimise impairment in appropriately targeted patients suffering from stroke.

Adaptation, Physiological↗

Neural control of canine colon motor function: studies in vivo.

The responses of the circular muscle of canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vivo. In vivo studies were carried out using close intra-arterial injections and local field stimulation of proximal, mid-, and distal colon while recording circumferential contractions. Our results suggest that acetylcholine is the major excitatory mediator, but another excitatory mediator could be released by high frequency field stimulation after atropine. Norepinephrine had mixed inhibitory and excitatory effects, but no evidence was obtained that it was released by field stimulation. Substance P had mainly excitatory effects partly by a mechanism involving nerves and partly by a direct effect on muscle; it in addition to norepinephrine deserves further evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. There is no explanation of the inhibition it produced after initial excitation during field stimulation. Vasoactive intestinal peptide had inhibitory effects but these were incomplete and inconsistent. This may be related to our inability to demonstrate relaxation or inhibition to field stimulation after atropine. Further evaluation of the possible role of vasoactive intestinal peptide and other agents as nonadrenergic, noncholinergic inhibitory mediators is required.

Animals↗

Neural control of canine colon motor function: studies in vitro.

The responses of strips of the canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vitro. Studies were carried out using longitudinal and circular muscle strips from proximal and distal colon with field stimulation and addition of agents to the bath. Overall, these and other studies in vivo suggested that acetylcholine was an ubiquitous mediator of neural excitation. Norepinephrine had mixed inhibitory and excitatory effects, the latter only in circular muscle. Inhibitory effects of norepinephrine seemed to be both pre- and post-synaptic but no evidence that it was released by field stimulation was obtained. Substance P had excitatory effects chiefly by release of acetylcholine. It, in addition to norepinephrine, at least in circular muscle, deserves evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. Although vasoactive intestinal peptide sometimes had inhibitory effects, these were incomplete and inconsistent. However, further evaluation of its possible role as a nonadrenergic, noncholinergic inhibitory mediator is required to determine if it is involved as one component in the response. Few qualitative differences existed between responses of various regions of the colon to potential neuromediators, although there were some consistent differences between responses of longitudinal and circular muscle. Some differences existed in responses obtained earlier in vivo and in vitro. In particular, inhibitory effects following excitation by substance P on field stimulation were found only in vivo. Nonadrenergic, noncholinergic inhibitory responses to field stimulation were consistently present only in vitro. These differences have not been explained.

Animals↗

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers.

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

Adolescent↗

Alterations in motor function of the small intestine from intravenous and intraluminal cholecystokinin.

Cholecystokinin has been found within the lumen of the gastrointestinal tract; however, its effect on intestinal motility has not been studied. We examined the effect of intraluminal and intravenous infusion of the octapeptide of cholecystokinin (CCK-OP) on myoelectric activity in the intestine of rabbits. CCK-OP was infused intraluminally at 1,000 ng X kg-1 X h-1, and portal venous blood samples were obtained hourly for plasma immunoreactive CCK. CCK-OP was also infused intravenously at a similar rate, and hourly peripheral venous blood samples were obtained for plasma immunoreactive CCK. Myoelectric activity was monitored in a 12-cm ligated ileal segment and the proximal adjacent small intestine after the infusion of intraluminal or intravenous CCK-OP. Intraluminal infusion of CCK-OP caused a significant increase (P less than 0.01) in both migrating action potential complexes (MAPC) and repetitive bursts of action potentials (RBAP) (3.1 +/- 0.8 MAPC/h and 4.6 +/- 1.3 RBAP/h). In contrast, intravenous CCK-OP induced only repetitive bursts of action potentials (8.3 +/- 1.7 RBAP/h, P less than 0.01). In summary, alterations in intestinal motility may vary according to the route of administration of the individual peptide. Furthermore, results from these studies suggest that intraluminal release of regulatory peptides may be important in the modulation of intestinal motility.

Action Potentials↗

Effect of ethyl alcohol on motor function in canine stomach.

The aim of this study was to elucidate the effects of ethanol on gastric emptying and the trituration of solid food. With the use of a noninvasive physiological imaging technique, gastric processing of a radiolabeled solid meal was evaluated in unanesthetized dogs which ingested 6-8% ethanol solutions or received intravenous alcohol before the meal. Oral alcohol (resulting in blood levels up to 174 mg/dl) decreased the amplitude of antral contractions or completely abolished them. Alcohol did not significantly affect the fundamental frequency of contractions except at high doses, at which contractions were abolished. Alcohol lengthened the mean time to 50% of gastric emptying in a dose-dependent manner, from 132 +/- 3 min without alcohol to 160 +/- 10 min with oral alcohol at blood levels of 80-120 mg/dl (P less than 0.05). This was manifested by a lengthening of the lag phase, but there was no effect on the terminal slope of emptying (emptying rate) of the processed meal. At equal blood levels up to 120 mg/dl, orally administered alcohol had a more pronounced effect than intravenous alcohol. These data suggest that even low doses of dilute alcohol affect the ability of the antrum to process solid food and thereby contribute to impairment of gastric emptying.

Administration, Oral↗

Evaluation of human postprandial antral motor function using ultrasound.

We used high-resolution ultrasound to characterize postprandial antral excursion characteristics in 15 healthy volunteers. Antral circumference was repeatedly measured in the sagittal plane anterior to the abdominal aorta, at 15-min intervals following ingestion of a standard meal. At each recording period, the maximal and minimal antral circumference was noted. In seven volunteers, antral circumference was studied continuously for 5 min at each 15-min recording period to assess the frequency and regularity of antral excursions. Antral circumference increased immediately after meal ingestion from preprandial values of 64 +/- 2.6 (means +/- SE) to 138 +/- 3.1 mm and then gradually decreased with meal emptying to 72 +/- 2.6 mm at 90 min. The continuous recordings of antral images revealed that antral circumference transiently decreased at regular intervals; the interval between successive excursions was 20.1 +/- 0.2 s. There was no change in the excursion interval with emptying. The excursion amplitude decreased from 33 +/- 3.9 mm immediately post-meal ingestion to 13 +/- 1.5 mm at 90 min (r2 = 0.62 +/- 0.07). The ratio between the excursion amplitude and circumference of the relaxed antrum changed only slightly with time (slope = 0.0009 +/- 0.00003). Comparison of repeat studies in 10 volunteers showed a low intra-individual variation for postprandial antral circumference and excursion amplitude.

Adult↗

Role of cGMP as a mediator of nerve-induced motor functions of the opossum esophagus.

Stimulation of esophageal nerves produces biphasic relaxation of the lower esophageal sphincter (LES) and an off response of circular esophageal muscle. Previously, we proposed that cGMP mediates nerve-induced hyperpolarization of circular LES muscle but not LES relaxation. These experiments explore whether cGMP mediates LES relaxation or the off response. Strips of muscle from the opossum esophagus and LES were connected to force-displacement transducers, placed in tissue baths containing oxygenated Krebs solution at 37 degrees C, and stimulated by an electrical field. 1H-[1,2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of guanylyl cyclase, antagonized the off response, shortened its latency, and blocked the first phase of LES relaxation. ODQ also antagonized LES relaxation by exogenous nitric oxide (NO) but not relaxations by vasoactive intestinal polypeptide (VIP). Part of the nerve-induced LES relaxation and the off response appear to be mediated by the second messenger cGMP. These studies indicate that VIP-induced LES relaxation is not mediated by cGMP and therefore do not support the hypothesis that VIP produces LES relaxation by causing the generation of NO.

Animals↗