Antral Waves Research Articles

O-112 Outcomes of random-start ovarian stimulation protocols as a possible evidence of the theory of antral follicles continuous recruitment

Abstract Study question We tried to validate the possibility and efficiency of ovarian stimulation (OS) started on any day of the menstrual cycle, based on a theory of continuous recruitment of antral follicles. Summary answer Formation of a pool of follicles with higher sensitivity to gonadotropic stimulation occurs several times during the menstrual cycle (MC). What is known already According to classical concepts and fundamental positions formulated in the middle of the last century, follicular recruitment occurs only once during the menstrual cycle - in the early follicular phase. Nowadays there is increasing evidence to suggest that there are multiple (two or three) antral follicular waves of recruitment during the MC. Also some researchers state that the process of follicle recruitment is continuous. Study design, size, duration This prospective clinical study was conducted at the V.I. Kulakov NMRC for OG&Pof Russia. The study included female cancer patients seeking retrieval and cryopreservation of oocytes and/or embryos before cancer treatment. 240 patients were selected for the study. The patients were divided into 5 groups depending on the cycle day on the moment when ovarian stimulation was initiated. All patients signed an informed consent form approved by the Ethics Committee. Participants/materials, setting, methods The 1st group consisted of patients who started standart OS from 1 to 5 days of the cycle (n = 65); the 2nd - from 6 to 10 (n = 36), the 3rd - from 11 to 15 (n = 45), the 4th - from 16 to 22 (n = 44), the 5th - from 23 to 28 (n = 50). In the late follicular and luteal phase we performed OS without a pituitary modulator. The comparative analysis included features of oo-, embryogenesis and steroidogenesis. Main results and the role of chance The mean age, BMI and AMH were not different among groups. There were no LH rise or OHSS signs noticed in any groups, despite that OS in late follicular and luteal phase of the MC was performed with no GnRH antagonist addition.There was no statistically significant difference in the duration of stimulation, starting doses, total dose of FSH and HMG. The largest number of oocyte cumulus complexes was obtained in the 5th group (11 (9–21) vs 7 (3,5–15,5) in the 1st group, p = 0,030). The greatest number of mature oocytes was obtained in the 4th and 1st groups. In the 2nd group the largest number of immature oocytes was obtained (37 (9.1%)). A smaller number of mature oocytes (165 (61.8%) vs 492 (72.9%) and 314 (77.5%), p = 0.001) was obtained in group 2 (compared with the 1st and the 4th groups), when stimulation was started in the presence of a dominant follicle . These periods coincided with higher estradiol and lower FSH serum levels. Based on our data the optimal moment for effective OS initiation starts with the decrease in serum estradiol which is approximately 48 hours before the menstrual bleeding. Limitations, reasons for caution The presented results could be applied mainly to young patients with high and normal ovarian reserve, who were in the main study group. In patients with low ovarian reserve, short menstrual cycle and early ovulation an issue of favorable time points for the initiation of OS should be resolved individually. Wider implications of the findings The data collected during our research could possibly contribute to future personification of OS protocols. Tailoring the ovarian stimulation protocols to the needs of the patients could decrease time needed for completing the protocol without affecting oocyte yield or their maturity. Trial registration number none

Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling.

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm2) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.

Modulation of individual components of gastric motor response to duodenal glucose

To evaluate individual components of the antro-pyloro-duodenal (APD) motor response to graded small intestinal glucose infusions in healthy humans. APD manometry was performed in 15 healthy subjects (12 male; 40 ± 5 years, body mass index 26.5 ± 1.6 kg/m(2)) during four 20-min intraduodenal infusions of glucose at 0, 0.5, 1.0 and 1.5 kcal/min, in a randomised double-blinded fashion. Glucose solutions were infused at a rate of 1 mL/min and separated by 40-min "wash-out" period. Data are mean ± SE. Inferential analyses are repeated measure analysis of variance with Bonferroni post-hoc testing. At 0 kcal/min frequency of pressure waves were: antrum (7.5 ± 1.8 waves/20 min) and isolated pyloric pressure waves (IPPWs) (8.0 ± 2.3 waves/20 min) with pyloric tone (0.0 ± 0.9 mmHg). Intraduodenal glucose infusion acutely increased IPPW frequency (P < 0.001) and pyloric tone (P = 0.015), and decreased antral wave frequency (P = 0.007) in a dose-dependent fashion. A threshold for stimulation was observed at 1.0 kcal/min for pyloric phasic pressure waves (P = 0.002) and 1.5 kcal/min for pyloric tone and antral contractility. There is hierarchy for the activation of gastrointestinal motor responses to duodenal glucose infusion. An increase in IPPWs is the first response observed.

GLP‐1 regulates gastroduodenal motility involving cholinergic pathways

The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.

Effects of intraluminal local anesthetic on upper gastrointestinal motor, sensory, and peptide hormone responses to intraduodenal glucose

Enterally administered glucose modifies gut sensation, diminishes hunger, and slows gastric emptying by suppressing antral motility and stimulating pyloric pressures. We aimed to clarify the mechanism of small intestinal glucose sensing. We studied eight healthy males twice, in random order. An antroduodenal manometry catheter was positioned with a sleeve sensor across the pylorus. Benzocaine, or vehicle alone, was given into the proximal duodenum as a bolus, followed by continuous infusion for 105 min (T=-15 to 90 min). Glucose was also infused into the proximal duodenum at 3 kcal/min for 90 min (T=0-90 min). Sensations of hunger, bloating, and nausea were assessed with visual analog questionnaires, blood was sampled at intervals, and energy intake at a buffet meal (T=90-120 min) was measured. Perceptions of bloating and nausea were markedly less with benzocaine when compared with vehicle (P<0.05 for each), with no difference in hunger, or energy intake. In contrast, the suppression of antral waves and stimulation of phasic and tonic pyloric pressures, duodenal waves, and propagated duodenal wave sequences by intraduodenal glucose infusion did not differ between the 2 days. No difference in blood glucose, plasma insulin, or plasma glucagon-like peptide 1 between benzocaine and control was observed, whereas glucose-dependent insulinotropic polypeptide and cholecystokinin concentrations were slightly higher with benzocaine (P<0.05 for both). Mucosal anesthesia ameliorates unpleasant sensations induced by enteral glucose, but does not inhibit the release of gut peptides that feed back on appetite and gastroduodenal motility.

Diminished functional association between proximal and distal gastric motility in critically ill patients

This study examined the effects of critical illness on the relationship between proximal and distal gastric motor activity during fasting and duodenal nutrient stimulation. Prospective, case-controlled study. Ten critically ill patients and ten healthy volunteers. Concurrent proximal gastric (barostat) and antro-pyloro-duodenal (manometry) motility were recorded during fasting and during two 60-min duodenal nutrient infusions (Ensure at 1 kcal/min and 2 kcal/min) in random order, separated by a 2-h wash-out period. Baseline proximal gastric volumes were similar between the two groups. At 10 min nutrient-induced fundic relaxation was lower in patients than healthy subjects (45 +/- 26 vs. 196 +/- 29 ml). In patients the frequency and volume amplitude of fundic waves were also lower. There were fewer propagated antral waves in patients than in healthy subjects during both fasting and nutrient infusion. These were more retrograde, shorter in length and associated with a pyloric contraction. The proportion of fundic waves followed by a distally propagated antral wave was significantly less in patients (0%, 0-8%) than controls 36% (11-44%). In critical illness, in addition to impairment of proximal and distal gastric motor activity, the association between the two gastric regions is abnormal. This disturbance may interfere with meal distribution and further contribute to slow gastric emptying in these patients.

Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans

A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor patterns in stomach and small intestine

The frequency and propagation velocity of distension-induced peristaltic contractions in the antrum and duodenum are distinctly different and depend on activation of intrinsic excitatory motoneurons as well as pacemaker cells, the interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because ICC are critical for coordination of motor activities along the long axis of many regions in the gut, the role of ICC in antroduodenal coordination was investigated. We used immunohistochemistry, electron microscopy, simultaneous multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and rats. A strongly reduced number of ICC-AP with loss of network characteristics was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3 mm in mice. Between antrum and duodenum, there was no interaction of electrical activities and in the absence of gastric emptying, there was no coordination of motor activities. When the pyloric sphincter opened, 2.4 s before the front of the antral wave reached the pylorus, the duodenum distended after receiving gastric content and aboral duodenal peristalsis was initiated, often disrupting other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric region allows the antrum and duodenum to have distinct uncoordinated motor activities. Coordination of aborally propagating peristaltic antral and duodenal activity is initiated by opening of the pylorus, which is followed by distention-induced duodenal peristalsis. Throughout this coordinated motor activity, the pacemaker systems in antrum and duodenum remain independent.

Upper gastrointestinal responses to intraduodenal nutrient in type 1 diabetes mellitus

Abnormal nutrient-related small-intestinal feedback may contribute to disordered gastric motility and upper gastrointestinal symptoms in patients with diabetes. To evaluate the motor, sensory and incretin responses to intraduodenal nutrients in patients with type 1 diabetes and in controls. Eight type 1 diabetes patients (two with autonomic neuropathy) and nine controls were studied during euglycaemia. A manometric catheter was positioned across the pylorus, and nutrient was infused intraduodenally (90 kcal over 30 min). Blood glucose and plasma glucagon-like peptide 1 and gastric inhibitory polypeptide were measured, and sensations were assessed with visual analogue questionnaires. During nutrient infusion, neither the number of antral waves nor the stimulation of phasic or basal pyloric pressures differed between patients and controls. Upper gut sensations and areas under the plasma incretin peptide curves did not differ between the groups. During euglycaemia, the upper gastrointestinal motor, sensory and incretin peptide responses to small-intestinal nutrient are comparable in patients with relatively uncomplicated type 1 diabetes and in healthy subjects.

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.

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

BACKGROUNDGlucagon-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.AIMSTo investigate the effects of GLP-1 on...

Influence of antral contraction waves on intragastric pressure, fluid motions and mixing

Influence of antral contraction waves on intragastric pressure, fluid motions and mixing

Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility

Background/Aims: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated. Methods: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects. Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h. A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities. Results: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I. A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline. Conclusion: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves. These motor effects of CLA suggest potential therapeutic applications.

Physiological changes in blood glucose affect appetite and pyloric motility during intraduodenal lipid infusion.

We evaluated the effects of varying blood glucose concentration within the normal postprandial range and its interaction with small intestinal nutrients on antropyloric motility and appetite. Eight healthy males (19-40 yr) underwent paired studies, with a blood glucose level of 5 or 8 mmol/l. Manometry and visual analog scales were used to assess motility and appetite, during fasting and intraduodenal lipid infusion (1.5 kcal/min). In the fasting state, antral waves were suppressed at 8 mmol/l compared with 5 mmol/l (P = 0.018). However, pyloric motility was no different between the two blood glucose concentrations. Hunger was no different at 5 mmol/l compared with 8 mmol/l, but fullness was greater at 8 mmol/l (P = 0. 01). During intraduodenal lipid infusion, antral waves were suppressed (P < 0.035) and isolated pyloric pressure waves (IPPWs) were stimulated (P < 0.02) compared with during the fasting state, with no difference between blood glucose concentrations, although the temporal patterning of IPPWs varied between blood glucose concentrations. The amplitude of IPPWs was greater at 5 mmol/l compared with 8 mmol/l (P < 0.001), and hunger decreased at 8 mmol/l compared with 5 mmol/l (P = 0.02). We conclude that "physiological" hyperglycemia modifies gastric motor and sensory function and that synergy exists between blood glucose concentration and small intestinal nutrients in modulating gastric motility and appetite.

Antroduodenal motor effects of intravenous erythromycin in children with abnormalities of gastrointestinal motility.

The macrolide antibiotic erythromycin (EM) affects gastrointestinal motor activity by acting as agonist of motilin receptors located on the smooth muscle cells of the gastroduodenal tract. We studied the effect of intravenous EM on fasting antroduodenal motility in controls and children with gastrointestinal dysmotility. EM lactobionate (rate, 3.0 mg/kg/h) was infused intravenously while antroduodenal manometry was recorded in 10 controls, in 7 patients with functional dyspepsia and in 6 patients with gut pseudo-obstruction. The mean (SD) age (years) was 5.7 (1.4), 6.5 (2.4), and 6.7 (3.2), respectively. Manometry was performed by means of a four- or six-lumen catheter introduced through the nose and perfused with a low compliance pneumohydraulic system. Five controls received EM and five received saline. EM, infused 5 minutes after passage of an activity front (AF), induced in controls a premature antroduodenal AF occurring 15.4 +/- 3.2 minutes after starting infusion; no motor changes were seen after saline; duration and propagation velocity of EM-induced AFs did not differ from spontaneous AFs. In patients with functional dyspepsia EM induced various patterns such as premature antroduodenal AFs, antral phase III-like pattern with short duodenal bursts or prolonged phasic antral waves and no duodenal activity. In patients with neurogenic pseudo-obstruction rare or absent antral activity with incoordinated or absent duodenal activity was induced; no contractions were elicited in two patients with myogenic pseudo-obstruction. It is confirmed that EM, given at subtherapeutic doses, is a powerful prokinetic agent that can have clinical applications in patients with gastrointestinal dysmotility; however, the effect of the drug seems to be influenced by the nature of the underlying disorder.

Effects of duodenal distention on fasting and postprandial antropyloroduodenal motility in humans

Background/Aims: Mechanoreceptors in the proximal small intestine may play an important role in the regulation of gastric emptying. Balloon distention of the duodenum causes fundic relaxation. The purpose of the present study was to determine the effect of stimulation of duodenal mechanoreceptors on both fasting and postprandial antropyloroduodenal motility in humans. Methods: Antropyloroduodenal pressures were recorded in 12 healthy volunteers with a sleeve-sidehole assembly, incorporating two balloons 5 and 20 cm distal to the pylorus. Duplicate proximal and distal duodenal balloon distentions with 10, 20, and 30 mL of air for 2.5 minutes were performed separately and in randomized order both during fasting and after a meal. Results: During fasting, proximal and distal distention at all volumes increased the number of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05), and the response to proximal distention was greater (P < 0.05). Postprandially, proximal and distal distention increased basal pyloric pressure (P < 0.05) with a greater response to proximal distention (P < 0.05), but had no effect on isolated pyloric pressure waves. Both during fasting and postprandially, there were more synchronous and less antegrade antral waves during distention (P < 0.05). The number of duodenal pressure waves increased during proximal (P < 0.05) but not distal distention. Conclusions: Stimulation of duodenal mechanoreceptors by balloon distention has significant and region-dependent effects on antropyloroduodenal motility that vary between fasting and postprandial states.

Postprandial antropyloroduodenal motility and gastric emptying in gastroparesis--effects of cisapride.

There is little information about the organisation of antroduodenal contractions or pyloric motility in patients with gastroparesis. The mechanisms responsible for the acceleration of gastric emptying by cisapride in patients with gastroparesis are also poorly understood. Simultaneous manometric and scintigraphic recordings were performed in 12 patients with gastroparesis and nine healthy volunteers before and after cisapride administration. Antropyloroduodenal pressures were recorded with a sleeve/side hole manometric assembly and gastric emptying with a scintigraphic method. Thirty minutes after the solid component of the test meal had begun to empty from the stomach all subjects received 5 mg cisapride intravenously over 10 minutes and recordings continued for a further 60 minutes. In the 30 minutes before cisapride there was no significant difference in the number of antral pressure waves (median 20 v 33, NS), basal pyloric pressure, or the number of isolated pyloric pressure waves between patients and volunteers, but the number of antral waves of extent > or = 6 cm (median 1 v 5, p < 0.05) was less in the patients, as was gastric emptying (8% v 20%, p < 0.05). In the patients, there was no change in the number of antral waves after cisapride, but there was an increase in the number of antral waves > or = 6 cm in extent (median 7 v 1, p < 0.05) and in the rate of gastric emptying (26% v 8%, p < 0.01). In the healthy subjects, cisapride increased gastric emptying (31% v 20%, p < 0.05), but reduced the number of antral waves (10 v 33, p < 0.05). Cisapride had no significant effect on the number of antral waves of extent more than or equal to 6 cm (11 v 5, NS). The number of isolated pyloric pressure waves decreased after cisapride (4 v 11, p < 0.05). There was a relationship between gastric emptying and the number of antral pressure waves of extent more than or equal to 6 cm in both the patients (r=0.38, p<0.05) and healthy subjects (r=0.05, p<0.01). There was no significant relationship between gastric emptying and the number of antral waves. It is concluded that disturbance of the relationship between antral, pyloric, and duodenal pressure waves is a major abnormality of postprandial gastric motor function in patients with gastroparesis. The stimulation of antral pressure waves of extent more than or equal to 6 cm may contribute to the acceleration of gastric emptying produced by cisapride in patients with gastroparesis and in normal subjects.

Integration of canine proximal gastric, antral, pyloric, and proximal duodenal motility during fasting and after a liquid meal.

The aim was to investigate the integration of proximal gastric, antral, pyloric, and duodenal motility during fasting and after feeding. Using a proximal gastric barostat and a manometric assembly with an array of side holes astride the gastroduodenal junction, the gastrointestinal interdigestive migrating motor complex was detected in five of seven conscious fasting dogs. During phase III of the complex, which lasted a mean +/- SEM of 13 +/- 0.5 min, 9.6 +/- 0.9 volume waves were present in the proximal stomach. The volume waves were coordinated with clusters of antral waves 64 +/- 11% of the time and with inhibition of duodenal waves 91 +/- 3% of the time. A 300-ml calorie-dense liquid meal abolished the complex and promptly increased proximal gastric volume in five of six dogs. Volume waves were nearly completely suppressed, while antral waves decreased from 24 +/- 3.0 waves/10 min to 10 +/- 2.8 waves/10 min (P < 0.05) and isolated pyloric pressure waves increased from 7.2 +/- 2.8 waves/10 min to 22 +/- 3.3 waves/10 min (P < 0.005). In summary, proximal gastric motility was integrated with antral, pyloric, and duodenal motility under both fasting and fed conditions. The integrated patterns likely account for the efficient clearance of indigestible solids during fasting and the controlled emptying of nutrients with feeding.

Dual effects of cisapride on gastric emptying and antropyloroduodenal motility.

There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis.

Dopamine interrupts gastrointestinal fed motility pattern in humans

The aim of this study was to investigate the hypothesis that during the postprandial period in humans, dopamine interrupts the gastrointestinal motility pattern through a mechanism that is peptide-mediated. Fourteen normal human subjects were studied by means of intestinal manometry. After recording two consecutive migrating motor complexes a 900-kcal solid-liquid meal was given. In eight subjects 30 min after the meal, placebo or dopamine (5 micrograms/kg/min) was infused for 15 min and then the recording continued for 120 min. In the remaining six subjects dopamine was administered twice with a 90-min interval in between. In three subjects the first dopamine infusion after the meal was preceded by treatment with placebo, the second by domperidone (20 mg intravenous as bolus), in the other three subjects domperidone was given before the first dopamine infusion. Blood samples for the determination of somatostatin and motilin were drawn basally, during, and immediately after dopamine in seven subjects. The results show that dopamine interrupts the fed motility pattern, inhibiting the high antral waves, and activates a duodenal phase III of migrating motor complexes. The pretreatment with domperidone completely prevented the dopamine effect. Plasma levels of motilin increased significantly during dopamine, while somatostatin blood levels did not change. These findings support the hypothesis that a dopaminergic mechanism may modulate the cycling of duodenal motor complex in humans.