Pharmacological Modification of Gastric Emptying: Effects of Propantheline and Metoclopromide on Paracetamol Absorption

The rate of paracetamol absorption depends on the rate of gastric emptying. Propantheline delayed gastric emptying and markedly slowed the absorption of paracetamol in six convalescent hospital patients. Conversely, the absorption of paracetamol in five healthy volunteers was accelerated by metoclopramide, a drug which stimulates gastric emptying. The total 24-hour urinary excretion of paracetamol was not influenced by propantheline or metoclopramide. Other similar absorption interactions probably occur since drugs are poorly absorbed from the stomach and many therapeutic agents influence gastrointestinal motility.     

Gastric emptying rate in Pleuronectes platessa L.

X-ray studies of gastric emptying of Pleuronectes platessa force-fed a moist, artificial diet give the relationship:
where GET is gastric emptying time (h), S is meal size (g), W is body weight (g) and T is temperature (°C).
The corresponding gastric emptying curve is predicted to be:
where stomach contents (g net weight) are S ₀ at start and S_t at time th. Direct observations of residual stomach contents using serial slaughter are in close agreement with the predicted curve, save for small plaice (below 50 g body weight) which empty at only 50–60% of the rate found in larger fish.
The small effects of body weight on gastric emptying rate may reflect the relatively small role of the stomach [Volume (ml) = 0.024 body weight (g)] in digestion when compared with other flatfish.
The emptying curve established here can be used in field studies to estimate feeding rate on natural food items, provided fish greater than 50 g body weight are used and the energy density of the food is greater than 0.5 kcal/g wet weight. Smaller fish will have emptying rates which are only 30–60% of those found in larger fish; the change appears to be abrupt and corresponds to the size at which young plaice move offshore from their nursery grounds.     

Effect of Metoclopramide on Gastric Emptying during Labour

The effect of a single dose of metoclopramide (Maxolon) on the gastric emptying rate of a liquid test meal was measured in a group of parturient women by a double-sampling dye-dilution technique. The subjects were given either metoclopramide 10 mg or sterile water by intramuscular injection on a double-blind random basis at the start of the test. The gastric emptying rate was significantly increased in those women who had received the metoclopramide as compared with those who had received the placebo.     

Dietary daidzein decreases food intake accompanied with delayed gastric emptying in ovariectomized rats

ABSTRACT

We previously found that equol, a metabolite of intestinal bacterial conversion from soy isoflavone daidzein, has female-specific anorectic effects. In the present study, we used seven-week-old female ovariectomized (OVX) Sprague Dawley rats to test the hypothesis that the anorectic effect of dietary daidzein may be attributed to delayed gastric emptying. Results suggest that dietary daidzein delays gastric emptying and that it has an anorectic effect with residual gastric contents, but not without gastric contents. Dietary equol significantly decreased daily food intake in the OVX rats without sleeve gastrectomy, but not in those with sleeve gastrectomy, suggesting that the accumulation of food in the stomach is required for the anorectic effect of equol to occur. These results support the hypothesis that the anorectic effect of dietary daidzein is attributed to delayed gastric emptying.     

Gastric evacuation in the sandbar shark, Carcharhinus plumbeus

Sandbar sharks maintained in an enclosure in the natural environment were fed meals of soft blue crab, Callinectes sapidus , or menhaden, Brevoortia lyrannus , and were sacrificed at intervals after feeding to measure rates of gastric emptying. Regression analysis was used to evaluate the adequacy of various models in describing the decrease in stomach contents with time after feeding. A Gompertz growth curve provided the best fit to the data for both food types. This model suggests that gastric emptying is characterized by an initial lag phase during which evacuation rate increases, a period of maximal evacuation, and a decreasing evacuation rate during the later stages of digestion. Passage of food from the stomach was slow relative to other species of fish studied. The time required to evacuate 98% of a meal was 92–3 and 70–7 h for sharks fed menhaden and blue crab respectively. Evacuation rates did not differ between day and night periods.     

Gastrointestinal Effects of Metoclopramide in Man. In Vitro Experiments with Human Smooth Muscle Preparations

Metoclopramide (N-(diethylaminoethyl)-2-methoxy-4-amino-5-chlorobenzamide) has been investigated with human gastrointestinal smooth-muscle preparations in vitro. Small-intestinal and colonic circular muscle was contracted by metoclopramide. This effect was antagonized by atropine. Gastric and colonic longitudinal muscle was sensitized by metoclopramide to acetylcholine. Atropine acted here as a partial antagonist of metoclopramide.The interference of acetylcholine and metoclopramide is of a hitherto undescribed pharmacological type. The effects of metoclopramide in vivo—where its action is predominantly on the stomach and pylorus—are not fully explained by these in vitro experiments in which the effect was found to be most pronounced on the colon.     

The contribution of gastric emptying scintigraphy to the treatment of obesity with gastric bandage--preliminary results

Introduction: Gastric banding for morbid obesity is among the least mutilating of procedures used in bariatric surgery and is classified as a restrictive surgical method. Although it is widespread, so far, however the mechanism responsible has not been fully explained. Methods and results: The authors present the preliminary results from scintigraphic examination of the evacuation ability of the stomach using food labeled with (99m)Tc-colloid in six obese patients with a gastric bandage. This initial study showed that the functionality of the bandage demonstrated as a significant drop in body weight, is connected with slower evacuation of the stomach. However, the use of adjustable bandages would have significantly slowed and restricted the passage of food through the cardia of the stomach. Conclusions: Since it can be extremely difficult to adequately objectively determine the functionality of gastric bandages, evaluating the gastric emptying scintigraphy may be useful in fulfilling this purpose.     

Provocation of a paradoxical growth hormone response to corticotropin-releasing hormone by pretreatment with metoclopramide in patients with acromegaly and normal subjects

Two of 7 patients with acromegaly and one of 7 normal subjects exhibited a paradoxical rise in growth hormone (GH) to human corticotropin-releasing hormone (CRH) when pretreated with metoclopramide, although CRH alone did not induce an increase in GH. In one of these two patients with acromegaly, the GH increase to metoclopramide alone also reached the criteria of a paradoxical response. These two acromegalic patients showed a GH increase to metoclopramide pretreatment before and up to two months after surgery. In another acromegalic patient, whose GH level remained high 5 months after surgery, metoclopramide induced an increase in GH level, while in a patient who had an above-normal GH level 18 months after surgery, the resumption of physiological GH secretion after surgery was evidenced by a postoperative absence of a GH response to metoclopramide. It is suggested from these results that the GH response to metoclopramide and the metoclopramide-provoked GH response to CRH in patients with acromegaly result from the secretion of GH from nonadenomatous cells of the pituitary.     

Role of gastric emptying on ethanol poisoning in rats

Intraperitoneal glucose was demonstrated to significantly inhibit the absorption of ethanol ( 2 g/kg) administered orally to rats. The effect was due to slowed emptying of the stomach, verified by analysis of the stomach contents and of blood enthanol levels. The observation agrees with previous findings, according to which the rate of stomach emptying is inversely related to the blood glucose level. However, when glucose was given intravenously 15 minutes after oral administration of a lethal dose of ethanol (12.5 g/kg) no significant inhibition of ethanol absorption could be observed. Intravenous propantheline, pyrithioxine and methylene blue were also unable to prolong the survival time or to influence the lethal blood ethanol concentration (about 170 mmol/l) of the enthanol-poisoned rats.     

Gastric emptying time and absorption of simple and complex carbohydrates in Macaca mulatta

Recent studies of nonhuman primates have shown that the amount and type of dietary carbohydrate influences the development of atherosclerotic lesions. In an effort to examine the gastrointestinal handling of simple and complex carbohydrates, measurements of gastric emptying times and uptake of C¹⁴ labeled carbohydrates were made for six female Macaca mulatta. A significantly smaller volume of sucrose solutions remained in the stomach after 60 minutes than solutions containing an equal amount by weight of dextrin. Similarly, when solutions of equal osmotic pressures but unequal weights of sucrose and dextrin were used, a significantly smaller volume of the sucrose solution remained in the stomach after 60 minutes. These findings are consistent with the idea that breakdown of dextrin by pancreatic amylase results in an increase in osmotic pressure of the intestinal contents and a slowing of gastric emptying. No significant differences in the levels of glucose or total C¹⁴ labeled carbohydrates were found in the peripheral blood following ingestion of C¹⁴ labeled sucrose or dextrin. This finding suggests that although an initial difference in the rate of gastric emptying of these carbohydrates exists, other factors, such as the rate of production and activity of pancreatic amylase, activity of intestinal disaccharidases, and intestinal mucosal transport, tend to equalize the rate of absorption of these sugars.     

Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding.

A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.     

Controlled Trial of Metoclopramide in the Treatment of Flatulent Dyspepsia

A double-blind cross-over trial of metoclopramide (Maxolon) against placebo was undertaken in 42 patients with flatulent dyspepsia. A highly significant difference was found in favour of the active drug (P<0·01). The time at which the drug is given in relation to the meal and onset of symptoms is probably important. It is concluded that metoclopramide is effective in the short-term treatment of these symptoms but should be started only after thorough investigations have excluded more serious disease.     

Gastric flow and mixing studied using computer simulation

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High-resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two-dimensional computer model of the stomach was developed with the 'lattice-Boltzmann' numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde 'jets' through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well-defined 'zone of mixing', confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction-induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.     

Validation of the stomach-flushing technique for obtaining stomach contents of Penguins

The efficiency of the stomach flushing technique in obtaining complete stomach contents was tested on Little, Gentoo and Rockhopper Penguins. This technique was validated by feeding the penguins known amounts of fish and subsequently flushing their stomachs after specified time intervals. Examination of the contents showed that the method is effective and offers an alternative to killing penguins in order to obtain stomach contents. The effects of different states of stomach fullness on food recovery rates highlighted the necessity for multiple flushing. Quantitative information on the effect of time between feeding and stomach flushing on the recovery rates was also obtained. Where stomach contents were relatively undigested the rate of retrieval of fish was 90–100%, but this rate decreased with time and in no cases in which stomach contents were in advanced stage of digestion was the retrieval rate higher than 80^o. Inclusion of the Gentoo and Rockhopper Penguins in the validation trials showed that the size of the penguin does not affect recovery rate.     

Paracetamol as a Post Prandial Marker for Gastric Emptying,A Food-Drug Interaction on Absorption

The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying.

Trial Registration

ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780     

管状胃代食管术与全胃代食管术治疗食管癌的安全性与有效性对比

目的:对比管状胃代食管术与全胃代食管术治疗食管癌的安全性与有效性。方法:2005年1月到2015年2月选择我院收治的100例食管癌患者,根据随机数字表法分为治疗组与对照组各50例,所有患者都行食管癌切除术,同时对照组给予全胃代食管手术,治疗组给予管状胃代食管术,对两组患者围手术指标、并发症及生活质量状况进行观察比较。结果:所有患者完成手术,治疗组的手术时间、术中出血量、术后住院时间、术后胃肠减压时间及术后闭式引流时间都明显少于对照组(P0.05)。治疗组术后3个月反流性食管炎、胃排空障碍、胸胃综合征、吻合口狭窄、吻合口瘘等并发症发生情况明显少于对照组(P0.05),日常生活、一般状况、治疗相关症状、社会影响、情感活动评分都明显高于对照组(P0.05)。结论:相对于全胃代食管术,管状胃代食管术在治疗食管癌患者中的应用具有更好的安全性与有效性,值得进一步临床研究与推广。     

Inhibition of dopamine receptors in the stomach: An explanation of the gastrokinetic properties of domperidone

We investigated the effects of dopamine and secrenin on the motility of the isolated guinea pig stomach. Changes in intragastric volume were continously recorded as a measure of gastric motility. When 0.25 μg/ml dopamine was given intra-arterially (i.a.) via the coeliac axis, the stomach relaxed, its spontaneous activity decreased, and its content augmented. This effect of dopamine could be selectively inhibited by the dopamine antagonists haloperidol (0.16 μg/ml) and domperidone (0.16 μg/ml); the latter is effective in the treatment of gastro-intestinal dysfunction. These observations demonstrate the presence of dopaminergic receptors in the guinea pig stomach. Similar conclusions can be reached for the rat stomach from ³H-domperidone displacement studies. Secretin (6.7 mU/ml i.a.) inhibited the vagally induced emptying of the stomach. This effect is reversed by domperidone (0.04 μg/ml). These results strongly suggest that dopamine or/and secretin are involved in the local feedback control of gastric motility; the action of secretin may be direct or indirect by release of dopamine. The local interference of domperidone with endogenous secretin and dopamine in the stomach may explain its gastrokinetic properties.     

Theory of gastric function

On the basis of some assumptions concerning gastric emptying a theory of gastric function is developed which explains the known facts —chiefly the emptying of liquids according to an exponential law. On the basis of this theory an equation is derived which relates the rate of secretion to the quantity of liquid retained in the stomach after a certain time. A study is made of the general characteristics of this equation. Some assumptions concerning different formulae describing the rate of secretion are found useful in experimental investigations, particularly in Hollander’s dilution indicator method.     

Pharmacological difference of L-dopa,apomorphine, and bromocriptine against metoclopramide

Rat prolactin was stimulated by metoclopramide and inhibited by L-dopa, apomorphine and bromocriptine. Depending on the order of administration, the efficiency of bromocriptine deviated from L-dopa and apomorphine in opposite directions. When injected into rats 15 min after metoclopramide, bromocriptine was much less effective than L-dopa and apomorphine in blocking the effect of metoclopramide on serum prolactin. When injected into rats 15 min before metoclopramide, bromocriptine was the most effective antagonist of metoclopramide action. A plausible explanation of these observations is that bromocriptine and metoclopramide are not strictly dopamine agonists and antagonists, while L-dopa and apomorphine act exclusively by a dopamine mechanism.     

胃多导电刺激及胃液体排空犬动物模型的建立

目的建立胃浆膜多导联电刺激和胃排空动物模型。方法在12条英国比格犬的胃大弯浆膜层包埋四对心内起搏电极,距幽门40cm空肠近端行一造瘘口。结果①造瘘管收集食糜的方法简单易行,通过其排空量,能了解不同的电刺激和不同的电刺激参数对胃动力的作用。②胃浆膜多导联电极记录的胃体、胃窦慢波电信号清晰、稳定,能准确地记录不同时间和不同实验的胃慢波变化。③单导联和多导长脉冲电刺激均能控制胃慢波。结论胃浆膜多导联电极是研究胃电生理、胃电起搏及胃电起搏对胃排空的影响较理想的方法。英国比格犬是此模型的理想材料。