Neural reflex of the canine pylorus to intraduodenal acid infusion

In 29 chloralose-urethane anesthetized dogs, a manometric assembly was inserted through a gastrostomy to monitor pressure of the pyloric region with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric sideholes and serosal strain gauges. An additional tube channel allowed intraduodenal infusions 1-2 cm aborad from the pylorus. Intraluminal infusion of hydrochloric acid (0.1 N, 0.92 ml/min, for 2 min) reproducibly caused activation of motor activity in the pyloric region and peristaltic duodenal activity. Proximal duodenal activity probably contributed to the total phasic response recorded in the pylorus region. Excitatory responses could also be elicited by infusion of phenyl-biguanide (stimulant of sensory nerve endings), but not by control infusions with diluent (Krebs' buffer or saline). The motor response of the pyloric region to intraduodenal acid was blocked by intraduodenal application of 2% xylocaine. Atropine (30 micrograms/kg i.v. and 100 micrograms i.a.) or hexamethonium (10 mg/kg and 1 mg i.a.) markedly reduced or blocked the acid-induced pyloric motor response of this region but propranolol (1.0 mg/kg i.v. and 100 micrograms i.a.), phentolamine (1.5 mg/kg i.v. and 100 micrograms i.a.), or naloxone (200 micrograms/kg and 20 micrograms i.a.) had no effect. We believe these observations show the existence of a reflex from the duodenum to the pylorus in response to intraluminal stimuli mediated by a chain of cholinergic nerves. In the dog, endogenous opioid peptides do not contribute to the excitatory reflex pathway activated by intraduodenal acid or phenyl-biguanide. As intraluminal acid in the duodenum activates this reflex, it may play a role in the physiologic and pathophysiologic role of gastric emptying in this species.     

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.     

Stimulation of pyloric contractions by intraduodenal triglyceride is persistent and sensitive to atropine

Intraduodenal lipid infusion stimulates phasic and tonic pyloric contractions and suppresses antral contractions. This study determined: (i) whether this response is sustained over 90 min; and (ii) the role of muscarinic mediation of this response. Antropyloroduodenal motility was recorded in 17 healthy volunteers with a sleeve/sidehole manometric assembly. Subjects received either a 90 min intraduodenal infusion of saline or triglyceride (20% Intralipid) at a rate of 1 mL/min; 30 min after the start of this infusion, the eight subjects who received triglyceride were given intravenous atropine 15 micrograms/kg over 30 s, followed by a maintenance infusion of 4 micrograms/kg/h until the study was completed. Intraduodenal triglyceride infusion stimulated isolated pyloric pressure waves consistently, producing a median rate of 2.4 per min after 30 min of triglyceride infusion, compared with a median rate of 0 per min pre-infusion. In intravenous saline studies, there was a reduction (P < 0.05) in the median rate of isolated pyloric pressure waves to 1.3 per min at 90 min, when compared with pyloric pressure waves at 30 min. Atropine reduced isolated pyloric pressure waves to a median rate of 0 per min, significantly different from preatropine (P < 0.01) and from intravenous saline studies (P < 0.0001). These results indicate that the phasic pyloric response to intraduodenal lipid persists during 90 min stimulation, albeit with significant attenuation. In humans, muscarinic cholinergic blockade prevents the occurrence of triglyceride stimulated localized pyloric contractions.     

Relation of pyloric motility to pyloric opening and closure in healthy subjects.

The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and a sleeve sensor positioned astride the pylorus. Simultaneous with manometry, pyloric opening and closure and antroduodenal contractions were observed fluoroscopically with the antrum filled with barium. During intraduodenal normal saline infusion, coordinated antral pressure waves swept over the pylorus and ejected barium into the duodenum. No localised pyloric motor pattern was observed under these conditions. In contrast, the intraduodenal triglyceride infusion was associated with the absence of antral pressure waves and virtual absence of antral wall movement. At the pylorus, there was a zone of luminal occlusion less than 1 cm long that persisted for the period of observation. This zone of luminal occlusion corresponded precisely with manometric recordings of a narrow zone of pyloric phasic and tonic activity. During the duodenal triglyceride infusion, the pylorus was closed for 98.5% of the measurement period when basal pyloric pressure was 4 mm Hg or more, and during this motor pattern, barium did not traverse the pylorus. Localised pyloric contractions cause sustained pyloric closure, whether these contractions are phasic or tonic. These contractions occur independently of antral or duodenal contractions and may interrupt gastric emptying.     

Pyloric motor response to intraduodenal dextrose involves muscarinic mechanisms

The delivery of dextrose solutions to the duodenum is associated with the stimulation of phasic and tonic pyloric contraction. In this study, the effects of intravenous atropine on the antropyloroduodenal motor responses to intraduodenal infusions of 25% dextrose were assessed in 10 normal volunteers. Antropyloroduodenal pressures were recorded with a manometric assembly incorporating a sleeve sensor spanning the pylorus, and sideholes in the antrum and duodenum. In each experiment, three intraduodenal infusions of 25% dextrose were given at a rate of 4 ml/min, for a median duration of 19 min (range 17-20). During the second dextrose infusion, intravenous atropine was given as a bolus (15 micrograms/kg) followed by an infusion (4 micrograms/kg.min), which was continued until the end of each experiment. Before atropine was given, the pyloric motor response to the second dextrose infusion was not significantly different from the response to the first infusion, but after administration of atropine there was a rapid decrease in the rate of isolated pyloric pressure waves, from 0.8 to 0.1 per minute (p less than 0.05). The isolated pyloric pressure wave response to the third dextrose infusion was completely blocked, and there was a much smaller maximum increase in basal pyloric pressure compared with the first infusion (p less than 0.01). This study indicates that intraduodenal dextrose reproducibly stimulates isolated pyloric pressure waves and increases basal pyloric pressure by mechanisms that involve muscarinic receptors.     

Pyloric motility

Intraduodenal infusion of nutrients has been shown by intraluminal sleeve-sidehole manometry to suppress antral contractions and stimulate isolated pyloric pressure waves (IPPWs) in humans. It is still unresolved, whether these pyloric contractions occur within an otherwise quiescent zone of motor and electrical activity and whether the presence of the sleeve sensor itself affects this nutrient-associated response. In four conscious dogs, comparisons were made between paired recordings of myoelectrical and motor activities of the antropyloroduodenal region with serosal strain gauge transducers and extracellular bipolar electrodes in the presence and absence of an intraluminal manometric sleeve-sidehole assembly during intraduodenal infusions of saline and a triglyceride emulsion (Intralipid 10%, 0.5 kcal/min). Of 287 isolated pyloric pressure waves, detected by the manometric sleeve sensor, 75% were detected as isolated pyloric contractions by the strain gauge transducers and 72% occurred in the absence of electrical spike activity in the distal antrum or proximal duodenum. The lower incidence of isolated pyloric contractions (strain gauges) was related to: (1) insensitivity of the pyloric strain gauge transducer in comparison to the manometric sleeve sensor (10%), and (2) inability of the manometric sleeve-sidehole assembly to detect pressure waves in the distal antrum (7%) or proximal duodenum (8%) during antral or duodenal wall motion. The presence of the sleeve sensor itself did not affect the number of lipid-induced isolated pyloric contractions but increased their amplitude [median 9 (7–15) mN vs 4 (2–6) mN;P<0.05]. We conclude that: (1) most isolated pyloric pressure waves recorded by the manometric sleeve sensor represent contractions truly isolated to the pylorus, and (2) the presence of a sleeve sensor does not influence the number of isolated pyloric contractions.     

Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on antropyloroduodenal motility and appetite in response to intraduodenal lipid infusion in humans

BACKGROUND: Studies in animals indicate that endogenous nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans. METHODS: On 2 separate days, 8 healthy adult men received intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals. RESULTS: Intraduodenal lipid infusion was associated with increases in fullness (P < 0.05) and in frequency of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05); and decreases in hunger (P < 0.05) and in frequency of antral (P < 0.05) and duodenal (P < 0.05) pressure waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P < 0.05), but had no effect on antropyloroduodenal pressures or food intake. CONCLUSIONS: Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.     

Stereospecific Effects of Intraduodenal Tryptophan on Pyloric and Duodenal Motility in Humans

Edelbroek M, Sun W-M, Horowitz M, Dent J, Smout A, Akkermans L. Stereospecific effects of intraduodenal tryptophan on pyloric and duodenal motility in humans. Scand J Gastroenterol 1994;29: 1088-1095.

Background: L-Tryptophan delays gastric emptying in animals to a greater extent than D-tryptophan, but none of the possible motor mechanisms responsible for this stereospecific effect have been evaluated.

Methods: In 11 healthy volunteers antropyloroduodenal pressures were recorded in the fasted state with a sleeve/sidehole manometric assembly during 20-min intraduodenal infusions (2 ml-min^]) of isotonic L- AND D-tryptophan (50 mM, pH 5.7) and normal saline (pH 5.5), given in randomized order.

Results: Intraduodenal L-tryptophan increased basal pyloric pressure (p < 0.05), whereas D-tryptophan had no effect. In contrast, l- and D-tryptophan both stimulated (p < 0.05) localized phasic pyloric pressure waves, and there was no significant difference in the responses. The number of duodenal pressure waves was greater during infusion of L-tryptophan than during D-tryptophan (p<0.05).

Conclusion: We conclude that intraduodenal tryptophan has stereospecific effects on pyloric and duodenal motility. Although the precise contribution of these differential effects to gastric emptying remains to be clarified, they may be partialK responsible for the differences in gastric emptying of D-tryptophan and L-tryptophan.     

Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans

BACKGROUND: Glucagon-like peptide-1(7-36)amide (GLP-1) is a gut hormone released postprandially. Synthetic GLP-1 strongly inhibits gastric emptying in healthy subjects and in patients with diabetes mellitus. AIMS: To investigate the effects of GLP-1 on antro-pyloro-duodenal motility in humans. METHODS: Eleven healthy male volunteers were studied on two separate days. On the interdigestive study day, a basal period was followed by a 60 minute period of saline infusion and two further 60 minute periods of intravenous infusion of GLP-1 0.4 and 1.2 pmol/kg/min to achieve postprandial and supraphysiological plasma levels, respectively. On the postprandial study day, the same infusions were coadministered with intraduodenal lipid perfusion at 2.5 ml/min (2.5 kcal/min) followed by another 60 minutes of recording after cessation of GLP-1. Antro-pyloro-duodenal motility was measured by perfusion manometry. RESULTS: GLP-1 significantly inhibited the number and amplitudes of antral and duodenal contractions in the interdigestive state and after administration of duodenal lipid. It abolished interdigestive antral wave propagation. In the interdigestive state, GLP-1 dose dependently increased pyloric tone and significantly stimulated isolated pyloric pressure waves (IPPW). Pyloric tone increased with duodenal lipid, and this was further enhanced by GLP-1. GLP-1 transiently restored the initial IPPW response to duodenal lipid which had declined with lipid perfusion. Plasma levels of pancreatic polypeptide were dose dependently diminished by GLP-1 with and without duodenal lipid. CONCLUSIONS: GLP-1 inhibited antro-duodenal contractility and stimulated the tonic and phasic motility of the pylorus. These effects probably mediate delayed gastric emptying. Inhibition of efferent vagal activity may be an important mechanism. As postprandial plasma levels of GLP-1 are sufficient to appreciably affect motility, we believe that endogenous GLP-1 is a physiological regulator of motor activity in the antro-pyloro-duodenal region.     

Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenal lipid and antral tachygastria in conscious dog

The myoelectrical and motor response of the antropyloroduodenal region to intraduodenal nutrient stimulation or antral tachygastria represent useful models for, respectively, physiological and pathophysiological gastric stasis to test the efficacy of prokinetic drugs. We evaluated the effects of an intravenous bolus of cisapride (0.63 mg/kg) on the myoelectrical and motor response of the antropyloroduodenal region to an intraduodenal triglyceride emulsion (10% Intralipid, 0.5 ml/min) or antral tachygastria in conscious dogs. Intraduodenal lipid suppressed antral motility (P<0.05, compared to intraduodenal saline) and stimulated phasic pyloric contractions (P<0.01, compared to intraduodenal saline), a motor pattern known to be associated with delayed gastric emptying. During intraduodenal lipid stimulation cisapride virtually abolished all isolated pyloric motor events (P < 0.05) and stimulated antral and duodenal motility (P<0.05 for both) and antropyloroduodenal coordination (65% versus 15%;P<0.05). Antral tachygastria was associated with a higher number of isolated pyloric motor events in the fasted state [0.8 (0.7–1.1) per minute versus 0.2 (0–0.3) per minute;P<0.05], but not during intraduodenal lipid stimulation [1.1 (0.9–1.7) per minute versus 1.2 (1.0–1.9) per minute; NS]. Cisapride decreased the number and duration of spontaneous episodes of antral tachygastria during intraduodenal saline and lipid infusion (P<0.05 for both) and abolished the tachygastria-associated motor patterns. Cisapride induced a 20% decrease in the antral slow-wave frequency during intraduodenal saline and lipid, irrespective of gastric pacemaker rhythm. We conclude that: (1) cisapride overcomes feedback from small intestinal lipid receptors on myoelectrical and motor activities of the antropyloroduodenal region and decreases antral slow-wave frequency, and (2) cisapride inhibits antral tachygastria and tachygastria-associated motor patterns. These effects may contribute to the effective gastrokinetic properties of cisapride in physiological and certain forms of pathophysiological gastric stasis.This study was supported by a grant from the Netherlands Organization for Research, Council for Medical Research (NWO-GBMW; grant 900-522-082). Part of the results of this study were presented in abstract form at the Annual Meeting of the American Gastroenterological Association held in New Orleans (Gastroenterology 100:A440, 1991).     

Effects of the Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME) on Antropyloroduodenal Motility and Appetite in Response to Intraduodenal Lipid Infusion in Humans

Background: Studies in animals indicate that endogenous nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans. Methods: On 2 separate days, 8 healthy adult men received intravenous _L-NAME 180 µg/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals. Results: Intraduodenal lipid infusion was associated with increases in fullness (P &lt; 0.05) and in frequency of isolated pyloric pressure waves (P &lt; 0.05) and basal pyloric pressure (P &lt; 0.05); and decreases in hunger (P &lt; 0.05) and in frequency of antral (P &lt; 0.05) and duodenal (P &lt; 0.05) pressure waves. _L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P &lt; 0.05), but had no effect on antropyloroduodenal pressures or food intake. Conclusions: Intravenous administration of the systemic NO synthase inhibitor, _L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.     

The stimulation of antral motility by erythromycin is attenuated by hyperglycemia

OBJECTIVE: Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia. METHODS: A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min. RESULTS: Intravenous erythromycin increased the amplitude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and amplitude of duodenal waves did not differ between the two blood glucose concentrations. CONCLUSIONS: Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.     

Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans.

Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.     

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

The aim of this study was to define better the motor phenomena associated with the slowing of gastric emptying by a duodenal lipid infusion. Antral, pyloric and duodenal motility were recorded in 10 healthy subjects with a manometric assembly which incorporated multiple perfused side-holes and a sleeve sensor positioned astride the pylorus. The gastric emptying of a standard solid meal and the distribution of the ingesta between the proximal and distal stomach were monitored with a radionuclide technique. A triglyceride emulsion was infused into the duodenum for 45 min once 25% of the meal had emptied. The infusion caused significant slowing in the rate of gastric emptying (P less than 0.01). This slowing in gastric emptying was associated with the suppression of pressure waves in the distal antrum (P less than 0.01) and proximal duodenum (P less than 0.01), the induction of pressure waves isolated to a narrow pyloric segment (P less than 0.01), and a redistribution of ingesta from the distal to proximal stomach. These findings suggest that pressure waves isolated to the pylorus, changes in the intragastric distribution of ingested food, and changes in proximal duodenal motility may all act in concert with changes in antral motility to regulate the gastric emptying of solids.     

Effect of opiate and adrenergic blockers on the gut motor response to centrally acting stimuli

Labyrinthine stimulation and cold pain inhibit feeding antral pressure activity, delay gastric emptying, and increase blood concentrations of beta-endorphin and norepinephrine. Further, labyrinthine stimulation induces, in approximately one-third of healthy individuals, a migrating burst of motor activity in the proximal intestine that interrupts the normal fed pattern. Our hypothesis was that endogenous opiates and catecholamines act as mediators of such disruptive effects of centrally acting stressful stimuli on gut motility. Thus, we studied feeding gastrointestinal pressure activity in healthy volunteers who were exposed to labyrinthine stimulation or cold pressure test, or both (both stimuli being either in their active or in their control forms), while receiving an intravenous infusion of either placebo (saline), or an opioid blocker (naloxone), or a combination of alpha- and beta-adrenergic blockers (phentolamine and propranolol), or all the drugs together. Neither opioid nor adrenergic blockers affected motility during control stimulations. Active stressful stimuli (labyrinthine stimulation, cold pain, or both) significantly inhibited antral feeding activity (p less than 0.05), but these effects were prevented by concomitant infusion of naloxone (p less than 0.05). Adrenergic blockade also prevented the antral motor inhibition caused by stress (p less than 0.05), but it was more effective for cold pain than for labyrinthine stimulation, and, when performed concomitantly with opiate blockade, the preventive effects disappeared. Furthermore, during adrenergic blockade labyrinthine stimulation invariably induced the appearance of a migrating duodenal burst of motor activity. Neither opioid nor adrenergic blockers modified the stress-induced rise of plasma beta-endorphin and norepinephrine. Our results suggest that opioids and catecholamines are involved in the mediation of the disruptive effects induced by centrally acting stressful stimuli on postprandial motor activity in the proximal human gut.     

Stimulation of pyloric motility by intraduodenal dextrose in normal subjects.

Recent studies suggest that the pylorus may play an important role in the regulation of the gastric emptying of nutrient liquids in man. Dextrose solutions in the range 5-25 g/dl have been reported to empty from the human stomach at a constant caloric rate of 2.1 kcal/min. This study examined, in 12 healthy volunteers, the effects of intraduodenal dextrose on pyloric motility. Dextrose solutions, 5, 10, 15, and 25 gde/dl and saline solutions, 0.9 and 2.7 g/dl were infused into the duodenum at 4 ml/min for 10 minutes. Antral, pyloric, and duodenal motility were monitored with sideholes and a sleeve sensor positioned across the pylorus. Significant increases in the rate of isolated pyloric pressure waves and in basal pyloric pressure were seen with 15 and 25 g/dl dextrose (p less than 0.02) and 2.7 g/dl saline (p less than 0.05). The intensity and duration of the phasic and tonic pyloric motor responses to intraduodenal dextrose were dose dependent and correlated directly with the rate of calorie delivery (p less than 0.005 for each parameter). Intraduodenal delivery of dextrose at a rate in excess of 2.1 kcal/min stimulates both phasic and tonic pyloric contraction. These changes in pyloric motility may contribute to the close regulation of the emptying of dextrose from the stomach.     

Prolonged manometric study of the gastroduodenal junction in man.

A study of the motor activity of the gastroduodenal (GD) junction has been carried out on 8 subjects by using an original probe provided with a suction cup, that allows not only a duodenogastric (DG) pull-though, but also a prolonged recording of the pyloric, antral and duodenal motor activity, in basal condition and after intraduodenal instillation of HCl 0.1 N and intravenous infusion of cerulein. The position of the probe was controlled with fluoroscopy and transmural potential difference. The DG pull-through did not show a zone of high pressure at the GD junction, but the prolonged study showed, during HC1 and cerulein administrations, a significant increase of the pyloric tonus.     

Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects

The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.     

Small intestinal glucose absorption and duodenal motility in type 1 diabetes mellitus

OBJECTIVE: Small intestinal glucose absorption is increased in animal models of diabetes mellitus, but little data are available in humans. Small intestinal motility is reported to be frequently abnormal in patients with diabetes and could potentially affect glucose absorption. Our aim was to evaluate small intestinal glucose absorption and duodenal motor responses to intraduodenal nutrients, in patients with type 1 diabetes and controls. METHODS: Eight type 1 patients (two with autonomic neuropathy) and nine controls were studied during euglycemia. A manometric catheter was positioned across the pylorus, and nutrient infused intraduodenally (90 kcal over 30 min), followed by a bolus of 3-O-methylglucose (3-OMG). Blood was sampled to measure glucose and 3-OMG concentrations. RESULTS: During nutrient infusion, the number of duodenal waves did not differ between patients and controls. After the infusion, patients with diabetes had more propagated duodenal wave sequences (p < 0.05). The area under the plasma 3-OMG curve did not differ between the groups but correlated with both the blood glucose concentration at the time of 3-OMG administration (r = 0.64, p < 0.005) and the number of duodenal waves (r = 0.52, p < 0.05) and antegrade propagated duodenal sequences (r = 0.51, p < 0.05) preceding the 3-OMG bolus. CONCLUSIONS: During euglycemia, duodenal motor responses to small intestinal nutrient are comparable in patients with relatively uncomplicated type 1 diabetes and healthy subjects, but duodenal motility after nutrient infusion is increased in patients. Small intestinal glucose absorption is similar in patients and controls, but may be dependent on the blood glucose concentration and duodenal motor activity.     

Human duodenal motor activity in response to acid and different nutrients

Duodenal motor activity in response to intraduodenal infusion of small volumes of acid and nutrients of different chemical composition was studied in 10 healthy humans, using a water-perfused catheter incorporating 20 antropyloroduodenal sideholes. Saline and dextrose did not affect motility. Acid very rapidly (in 39 ± 11 sec) increased the number of pressure waves (P = 0.035) and antegradely propagated pressure waves (P = 0.02). After lipid infusion a considerable lag time (163 ± 81 sec) was observed, followed by a prominent increase in duodenal pressure waves (P = 0.02) and antegradely propagated pressure waves (P = 0.002). Furthermore, lipid-induced propagated pressure waves traveled over significantly longer distances (4.5 to 6 cm) than those induced by acid infusion (3 cm). We conclude that the motor response to small amounts of intraduodenal nutrients and acid is dependent on the chemical composition of the stimulus. The findings suggest that chemoreceptors in the duodenal wall provide input to local or regional control mechanisms involved in the regulation of duodenal motility.