Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome

BACKGROUND: Patients with irritable bowel syndrome (IBS) frequently complain of excessive gas but their fasting volume of intestinal gas is apparently normal. We hypothesised that the pathophysiological mechanism involved may be impairment of intestinal gas transit. AIM: To investigate intestinal gas transit and tolerance in IBS patients compared with healthy subjects. METHODS: A gas mixture (N(2), O(2), and CO(2) in venous proportions) was infused into the jejunum of 20 patients with IBS and 20 healthy controls at 12 ml/min for four hours. Gas evacuation, initially flatus from the anus (two hours) and then intrarectally (two hours), was continuously recorded. Symptom perception (0-6 scale) and abdominal distension were measured at 10 minute intervals. RESULTS: After two hours of external gas (flatus) collection, 18 of 20 IBS patients had developed gas retention (>400 ml), increased gastrointestinal symptoms (score >3), or abdominal distension (>3 mm girth increment) compared with only four of 20 control subjects. During intrarectal gas collection, 13 of 17 patients still exhibited abnormal responses. CONCLUSION: A large proportion of patients with IBS can be shown to have impaired transit and tolerance of intestinal gas loads. This anomaly may represent a possible mechanism of IBS symptoms, specifically pain and bloating.     

Gastric fundus relaxation and emetic sequences induced by apomorphine and intragastric lipid infusion in healthy humans

OBJECTIVES: Experimental animal studies have suggested that gastric relaxation precedes emesis, whether induced by peripheral or central stimuli. We aimed to quantify the gastric relaxatory and symptomatic responses to a standardized emetic inductor. METHODS: In healthy volunteers, we measured the gastric and symptomatic response to two different proemetic stimuli: a peripheral stimulus (intragastric infusion at 5 ml/min of 50% fat emulsion in water) and a central stimulus (s.c. apomorphine at 0.01 mg/kg). Proximal gastric tone was continuously recorded by an electronic barostat. Symptoms were simultaneously quantified by a graded questionnaire. RESULTS: Lipid-induced gastric relaxation occurred in 17/17 subjects and was followed by nausea in 12/17. The total amount of intragastric fat required to trigger gastric relaxation was 139 +/- 34 ml and to induce nausea, 258 +/- 32 ml. Gastric relaxation after subcutaneous apomorphine occurred in 13/14, and nausea/emesis, in the same 13/14. As expected, timing of events after stimulation was much shorter in response to the central than to the peripheral stimulus. Thus, gastric relaxation began 4.0 +/- 0.6 min after subcutaneous apomorphine and 28 +/- 7 min after the onset of lipid infusion (p < 0.05); likewise, the symptomatic response to central stimulation with apomorphine was 8.5 +/- 1.8 min versus 52 +/- 6 min for lipid infusion, p < 0.05. However, the magnitude of gastric relaxation was quite similar for both stimuli (apomorphine: 208 +/- 35 ml; intragastric lipid: 235 +/- 23 ml). No correlation was observed between the symptomatic response and the magnitude of the gastric relaxation, whether elicited by intragastric infusion of lipids or by subcutaneous apomorphine. Specifically, when symptomatic and gastric motor responses were compared in each of the 14 subjects who received both stimuli, no significant correlation between individual responses was detected. CONCLUSIONS: Gastric relaxation invariably precedes nausea and emesis and is of the same magnitude whether induced by apomorphine (central stimulus) or intragastric lipid infusion (peripheral stimulus). Nevertheless, in some instances and depending on the nature of the stimulus, fundic relaxation is a physiological event unassociated with nausea.     

Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion

OBJECTIVE: In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS. METHODS: In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0-6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days. RESULTS: IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 +/- 90 mL vs-210 +/- 105 mL in health, p < 0.05) but not during ileal infusion (-79 +/- 87 mL vs-79 +/- 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 +/- 3 mm girth increment vs 0 +/- 1 mm during ileal gas infusion and 1 +/- 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 +/- 0.6 score vs 2.6 +/- 0.7 score during ileal gas infusion and 1.6 +/- 0.5 score in health, p < 0.05 for both). CONCLUSIONS: In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects.     

Effect of gastric distension and duodenal fat infusion on biliary sphincter of oddi motility in healthy volunteers

Although sphincter of Oddi (SO) dysfunction has been implicated in the pathogenesis of postcholecystectomy syndrome and pancreatitis, little is known about normal physiologic stimuli, such as intraduodenal fat on human SO motility. Furthermore, gastric distension that frequently accompanies endoscopic manometry has been shown in animal studies to affect SO motility. We evaluated the effects of intraduodenal fat and gastric distension on SO basal pressure. Asymptomatic volunteers had SO manometry performed while sequentially performing gastric distension and intraduodenal fat perfusion. Five subjects (ages 29.8±4.8 years, range 22–35 years) had a mean basal sphincter of Oddi pressure of 23.4±5 mm Hg (range 17–31 mm Hg). Injection of air into the stomach caused no appreciable change in either intragastric pressure or SO pressure. Intraduodenal fat infusion resulted in a decrease in mean SO basal pressure from 23.4±5.0 to 4.4±4.4 mm Hg (P=0.004). These results demonstrate that gastric distension does not affect SO basal pressure and that intraduodenal fat infusion reduces SO basal pressure.This work was presented in part at the Digestive Disease Week in Boston, Massachusetts, in May 1993.This work was supported in part by a research award from the American Society of Gastrointestinal Endoscopy.     

Effect of misoprostol on postprandial intestinal motility and orocecal transit time in humans

We measured the effect of misoprostol (M), a PGE₁ analog, on duodenojejunal postprandial motor activity and orocecal transit in eight healthy volunteers. Intestinal motility was studied by an intraluminal catheter with three strain gauge transducers connected to a solid-state datalogger, and transit time was measured by a hydrogen breath test. Subjects were studied for two consecutive days and fed twice a day with a similar, 600-kcal meal. Misoprostol (M) at 800, 400, or 200 g or placebo were taken orally before every one of the four meals. Transit time was measured after the morning meal on both days, after ingestion of either 800 g of M or placebo. On four occasions, following M, the normal fed pattern was not established and the migrating motor complex (MMC) was not interrupted by the meal. In all other occasions, when the higher doses of M were given, the first 1–2 hr after the meal revealed a hypoactive bowel. This effect was inconsistently seen following 200 g of M. Orocecals transit time was consistently and significantly shorter after M than placebo: 48.3±9.5 min vs 104.4±4.8 min,P<0.0001. Four subjects had diarrhea during the study. We conclude that misoprostol, particularly at higher doses, has a profound effect on intestinal postprandial motility and results in accelerated transit time. The motility changes induced by M may be responsible, in part, for its effect on transit.A preliminary report of this work was given at the annual meeting of the American Gastroenterological Association, May 1991, and was published as an abstract inGastroenterology 100:496, 1990. This study was supported in part by Searle.     

Influence of body posture on intestinal transit of gas

BACKGROUND: Patients describe that body posture may affect their abdominal bloating, distension, and flatulence, but whether changes in position have objectively demonstrable effects, either beneficial or deleterious, has not been investigated. Aim: To determine the effect of body posture, upright versus supine, on intestinal transit of gas loads. SUBJECTS: Eight healthy subjects without gastrointestinal symptoms. METHODS: In each subject a gas mixture was continuously infused into the jejunum (12 ml/min) for three hours, and gas evacuation, clearance of a non- absorbable gaseous marker, perception, and abdominal girth were measured. Paired studies were randomly performed in each subject on separate days in the upright and supine positions. RESULTS: In the upright position, intestinal gas retention was much smaller than when supine (13 (52) ml v 146 (75) ml retention at 60 minutes, respectively; p<0.05), and clearance of the gas marker was expedited (72 (10)% clearance v 49 (16)% at 60 minutes, respectively; p<0.05). The gas challenge test was well tolerated both in the upright and supine positions without abdominal distension. CONCLUSION: Body posture has a significant influence on intestinal gas propulsion: transit is faster in the upright position than when supine.     

Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans

Objective. Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. Material and methods. Seven healthy male volunteers (18–27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of l-NMMA (4 mg kg^?1 h^?1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. Results. The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (l-NMMA versus saline 1.6±0.2 h versus 1.9±0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of l-NMMA compared with saline (l-NMMA versus saline 92.1±3.9 min versus 66.4±6.4 min; p<0.005). Infusion of l-NMMA significantly increased the frequency (l-NMMA versus saline 50.4±6.6 versus 34.8±5.5 waves per 30 min; p<0.05) and amplitude (l-NMMA versus saline 20.4±1.5 versus 15.5±1.1 mmHg; p<0.01) of duodenal pressure waves. Conclusions. These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.     

Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans

OBJECTIVE: Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. MATERIAL AND METHODS: Seven healthy male volunteers (18-27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of L-NMMA (4 mg kg-1 h-1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. RESULTS: The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (L-NMMA versus saline 1.6+/-0.2 h versus 1.9+/-0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of L-NMMA compared with saline (L-NMMA versus saline 92.1+/-3.9 min versus 66.4+/-6.4 min; p<0.005). Infusion of L-NMMA significantly increased the frequency (L-NMMA versus saline 50.4+/-6.6 versus 34.8+/-5.5 waves per 30 min; p<0.05) and amplitude (L-NMMA versus saline 20.4+/-1.5 versus 15.5+/-1.1 mmHg; p<0.01) of duodenal pressure waves. CONCLUSIONS: These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.     

Effects of physical activity on intestinal gas transit and evacuation in healthy subjects

PURPOSE: To determine the effects of mild physical activity on intestinal gas transit and clearance. METHODS: In 8 healthy adults, a gas mixture was infused continuously into the jejunum (12 mL/min) for 120 minutes with simultaneous duodenal lipid perfusion (1 kcal/min). Gas evacuation, perception of abdominal sensations (on a scale of 0 [none] to 6 [pain]), and abdominal girth were measured at 15-minute intervals during rest and intermittent pedalling, with subjects in a supine position. RESULTS: Mean (+/- SD) intestinal gas retention was lower during exercise than at rest (-84 +/- 303 mL vs. 143 +/- 219 mL, P <0.05). Gas retention during rest was associated with significant abdominal distension (8 +/- 6 mm, P <0.01 vs. basal), which was decreased with exercise (3 +/- 7 mm, P <0.05 vs. rest). The gas challenge test was well tolerated both during exercise and rest (perception score: 0.6 +/- 0.5 vs. 0.9 +/- 0.4, P = 0.25). CONCLUSION: In healthy subjects, gut transit of intraluminal gas is enhanced by mild physical activity.     

Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans

BACKGROUND AND AIMS: It is unclear whether fat digestion is required for the induction of gastrointestinal sensations and whether different fats have different effects. We investigated the effect of fat digestion and of medium-chain triglycerides (MCTs; C < 12) and long-chain triglycerides (LCTs; C > 16) on gastrointestinal sensations. METHODS: In a double-blind study, 15 healthy subjects were studied on 5 occasions during which LCT or MCT emulsions (2 kcal/min), with or without 120 mg tetrahydrolipstatin (THL, lipase inhibitor), or sucrose polyester (SPE, nondigestible fat) were infused intraduodenally in randomized order. After 30 minutes, the proximal stomach was distended in 1 mm Hg steps/min. Intensity of gastrointestinal sensations (on a 0-10 visual analog scale), plasma cholecystokinin (CCK) levels, and gastric volumes were assessed throughout. RESULTS: LCT and MCT increased gastric volume at baseline pressure compared with SPE, and LCT more than MCT. THL entirely abolished this effect (volumes [mL]: LCT, 213 +/- 19; LCT-THL, 39 +/- 3; MCT, 155 +/- 12; MCT-THL, 43 +/- 5; SPE, 44 +/- 5). Only LCT increased plasma CCK levels (pmol/L per 30 minutes: LCT, 21 +/- 2; LCT-THL, 9 +/- 1; MCT, 9 +/- 1; MCT-THL, 11 +/- 1; SPE, 9 +/- 1). During distentions, intragastric volumes were greater during infusion of LCT and MCT than during the respective THL conditions or SPE, but plasma CCK levels did not change. The intensity of sensations increased (hunger decreased) more with LCT than with MCT. During infusion of THL or SPE, the effects were smaller than during LCT or MCT. CONCLUSIONS: Fat digestion is required for the modulation of gastrointestinal sensations during gastric distention. The effects of fat depend on the fatty acid chain length and are not entirely explained by release of CCK.     

Impaired reflex control of intestinal gas transit in patients with abdominal bloating

BACKGROUND: Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. METHODS: In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. RESULTS: In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p<0.05 v sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension v 730 (183) ml during sham distension; NS; p<0.05 v healthy controls for both). CONCLUSION: Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.     

Gastric and duodenal ulcer

Die Wirkungen von Benzedrin und Pervitin auf die physische und psychische Leistungsfähigkeit sind in Versuchen an etwa 1400 jungen, gesunden, hochgradig ermüdeten Versuchspersonen, die in bis zu 3-tägigen Übungen ohne Schlaf ermüdet worden waren, studiert worden. Die Ergebnisse sind in den Zusammenfassungen der einzelnen Kapitel vorgelegt: I. Die Einwirkung von Benzedrin und Pervitin auf die körperliche Leistungsfähigkeit. II. Die Einwirkung von Benzedrin und Pervitin auf die psychische Leistungsfähigkeit (Bourdontests, Rechenaufgaben). Ein Beitrag zur Frage der Bedeutung des Ermüdungsgrades (und des Tagesrhytmus) für die Wirkung (Dosierung) des Benzedrins. III. Die Einwirkung von Benzedrin auf die Treffsicherheit ermüdeter Schützen beim Scheibenschiessen.     

Fundic balloon distension stimulates antral and duodenal motility in man

Distension of the intestine triggers the peristaltic reflex, which consists of orad contraction and aborad relaxation. Whether a similar response occurs in the human stomach is unclear. Our aim was to investigate the antral and duodenal motor response(s) to mechanical distension of the proximal stomach. In six healthy volunteers, a large compliant balloon was placed in the proximal stomach. Alongside this a water-perfused manometry probe with six sensors was placed to measure the antral and duodenal motility. Pressure activity was assessed before and during balloon distension. In five of six subjects, balloon distension triggered a salvo of antral pressure waves within 3–5 min, some of which propagated into the duodenum. The amplitude of waves was higher (P < 0.05) at the antrum than at the duodenum. The area under the curve of pressure waves was higher (P < 0.05) at the antrum than at the duodenum. In conclusion, distension of the proximal stomach, at or below the threshold for perception, evokes phasic motor activity in the antrum and duodenum. Thus, the gastric response to distension differs from that observed during the intestinal peristaltic reflex.     

Intralipid infusion into humans reduces in vitro platelet aggregation and alters platelet lipid composition

Intralipid (Kabi Vitrum Inc, Alameda, CA) infusion into normal volunteers results in substantial elevation in serum triglyceride, phospholipids, and free cholesterol concentrations. Platelet aggregation induced in vitro in platelet-rich plasma by collagen or ADP was significantly reduced by up to 40% and 45%, respectively, during the infusion period but returned to preinfusion levels 18 hours after the end of the infusion. In parallel, platelet lipid composition was also affected. Platelet free cholesterol content was reduced by up to 20% during the infusion of Intralipid, whereas platelet triglyceride and phospholipid contents increased by 3.5-fold and twofold, respectively. Eighteen hours after the end of the infusion, both platelet cholesterol and triglyceride returned to preinfusion levels, but platelet phospholipid was still elevated. Both components of Intralipid (liposomes and triglyceride-phospholipid particles) were able to decrease in vitro platelet aggregation and platelet cholesterol content. Our results demonstrate decreased platelet function induced by Intralipid infusion into humans, which was associated with reduced platelet cholesterol content. These results suggest possible antiatherogenic effects of infusing Intralipid in humans.