Prolongation of gastric emptying by oral propantheline.

The present study shows that a single oral recommended dose of propantheline bromide normally doubles the mean gastric half-emptying time in man. In a prospective, double-blind, randomized crossover design 13 normal subjects were given 30 mg propantheline or placebo 90 min before taking a 113m-indium-labeled liquid test meal, the volume of which was adjusted to body weight. The disappearance of radioisotope from the area of the stomach was determined by external gamma counting. After placebo the mean half-emptying time was 68 min and after propantheline it was 135 min (p less than 0.005). Although salivary flow decreased and pulse rate increased there were no visual disturbances. In studies already reported maximally tolerated oral doses of quaternary ammonium anticholinergic drugs have not consistently retarded gastric emptying in man.     

The influence of induced hyperglycaemia on gastric emptying rate in healthy humans

The effect on gastric emptying rate (GER) of elevated plasma glucose was investigated in eight healthy non-diabetics. They received intravenous infusions of 1000 ml 10% glucose (555 mmol, 1720 kJ) in 2 h: one-half before and the rest during the measure of GER. A control group was established with infusion of hypertonic sodium chloride and in a third group the GER was measured twice without infusion. GER was measured after 6 h of fasting, and following ingestion of a 100 g omelette (1400 kJ) tagged with 40 MBq 99mTc-sulphur colloid and 150 ml water with 8 MBq 111In-DPTA. Anterior and posterior recordings were made on gamma camera every 10th min during 1 h. Time-activity curves from the gastric area were generated for solid and liquid phases, respectively, using geometric means. The GER of solids was delayed, at least partly, by prolongation of the lag phase, and the GER of liquids was delayed following the intravenous infusion of glucose. The GER of solids was delayed following hypertonic saline infusion but not to the same extent as followed glucose in spite of the double osmotic load of saline. The percentage delay of GER of solids following glucose infusion was related to the increase in plasma glucose.     

Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.     

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between gastric emptying,plasma cholecystokinin,and peptide YY in critically ill patients

Background  

Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness.     

Predictors of delayed gastric emptying in diabetes.

OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.     

A pharmacological dose of glucagon suppresses gastric emptying of a radiolabelled solid meal in humans

The effect of glucagon (143 nmol i.v. bolus followed by 430 nmol infused at a constant rate over 90 min) vs placebo (normal saline) on gastric emptying was examined in a blind randomized study in eight healthy males. The gastric emptying of a radiolabelled solid meal was measured with the use of a gamma camera. Glucagon elicited a pronounced delay in gastric emptying in all subjects examined--mean gastric transit time MTT90 glucagon 44.2 +/- 0.22 min vs placebo 38.6 +/- 0.74 min, p less than 0.001.     

Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.     

Development of gastric emptying in the human fetus.

OBJECTIVE: To evaluate stomach size and the development of gastric emptying in human fetuses using ultrasound. DESIGN: Clinical observational study. METHODS: The motility and peristalsis of the fetal stomach were studied in 80 normal fetuses between 12 and 39 weeks of gestation. Fetal gastric motility was assessed by analysis of videotaped recordings of ultrasound images of the stomach taken in real time. RESULTS: Fetal maximum gastric area gradually increased and minimum gastric areas gradually decreased after 20 weeks of gestation. At term, the maximum and minimum gastric area ratios were approximately 13 and 5%, respectively. The change in fetal gastric area, defined as the difference of maximum and minimum gastric area ratios, was relatively constant at 3% from 12 to 15 weeks of gestation to 20-23 weeks of gestation. It increased significantly (to 8%) after 24-27 weeks of gestation until term. CONCLUSIONS: Fetal gastric emptying was quantified and its development assessed during pregnancy. A critical point of gastric development, associated with an increase in the change of gastric volume, was identified at 24-25 weeks of gestation.     

Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans.

It is known that the ingestion of glucose alone causes a greater increase in plasma glucose levels than ingestion of the same amount of glucose given with other nutrients. Since physiological plasma concentrations of cholecystokinin (CCK) prolong gastric emptying, it is proposed that after a meal, CCK may modify plasma glucose levels by delaying glucose delivery to the duodenum. To evaluate the effect of CCK on oral glucose tolerance, plasma CCK, insulin, and glucose levels and gastric emptying rates were measured in eight normal males before and after the ingestion of 60 g glucose with the simultaneous infusion of either saline or one of two doses of CCK-8 (12 or 24 pmol/kg per h). Gastric emptying rates were measured by gamma camera scintigraphy of technetium 99m sulfur colloid and plasma CCK levels were measured by a sensitive and specific bioassay. Basal CCK levels averaged 1.0 +/- 0.1 pM (mean +/- SEM, n = 8) and increased to 7.1 +/- 1.1 pM after a mixed liquid meal. After glucose ingestion, but without CCK infusion, CCK levels did not change from basal, and the gastric emptying t1/2 was 68 +/- 3 min. Plasma glucose levels increased from basal levels of 91 +/- 3.9 mg/dl to peak levels of 162 +/- 11 mg/dl and insulin levels increased from 10.7 +/- 1.8 microU/ml to peak levels of 58 +/- 11 microU/ml. After glucose ingestion, with CCK infused at 24 pmol/kg per h, plasma CCK levels increased to 8 pM and the gastric emptying t1/2 increased to 148 +/- 16 min. In concert with this delay in gastric emptying, peak glucose levels rose to only 129 +/- 17 mg% and peak insulin levels rose to only 24.2 +/- 4.2 microU/ml. With CCK at 12 pmol/kg per h, similar but less dramatic changes were seen. To demonstrate that endogenous CCK could modify the plasma glucose and insulin responses to oral glucose, oral glucose was given with 50 g of lipid containing long-chain triglycerides. This lipid increased peak CCK levels to 3.7 +/- 0.9 pM. Concomitant with this rise in CCK was a delay in gastric emptying and a lowering of plasma glucose and insulin values. To confirm that CCK reduced hyperglycemia by its effect on gastric motility, 36 g glucose was perfused directly into the duodenum through a nasal-duodenal feeding tube in four subjects. With duodenal perfusion of glucose, there was no change in plasma CCK levels, but plasma glucose levels increased from basal levels of 93+/-5 to 148+/-6 mg/dl and insulin levels rose from 10.6+/-3.5 to 29.5+/-5.2 microU/ml. When CCK was infused at 24 pmol/kg per h, neither the plasma glucose nor insulin responses to the duodenal administration of glucose were modified. Thus we conclude that CCK, in physiological concentrations, delays gastric emptying, slows the delivery of glucose to the duodenum, and reduces postprandial hyperglycemia. These data indicate, therefore, that CCK has a significant role in regulating glucose homeostasis in human.     

Infusion of cholecystokinin octapeptide in man: relation between plasma cholecystokinin concentrations and gallbladder emptying rates

To establish the sensitivity of the gallbladder in relation to plasma concentrations of cholecystokinin, a dose-response study was performed in five normal volunteers. Cholecystokinin octapeptide was infused in ascending incremental dose sequence, interval blood samples taken for estimation of plasma hormone concentrations and gallbladder emptying rates monitored continuously using 99mTc-HIDA. In five other volunteers, gallbladder emptying rates following a liquid fat meal were measured. Infusion rates of 0.0, 0.75 +/- 0.2, 6.8 +/- 0.5, 23.8 +/- 1.6 and 66.1 +/- 2.5 pmol cholecystokinin kg-1 h-1 produced plasma concentrations of less than 3.0 (undetectable), less than 3.0, 6.6 +/- 1.8, 13.3 +/- 1.5 and 26.9 +/- 2.9 pmol l-1 respectively and gallbladder emptying rates (% min-1) of 0.0, 0.0, 0.14 +/- 0.15, 1.57 +/- 0.38 and 4.29 +/- 1.12. Following the fat meal, peak plasma cholecystokinin concentrations reach 30 pmol l-1 and gallbladder emptying rates (% min-1) are 3.86 +/- 1.01. We conclude that the threshold of the gallbladder to circulating cholecystokinin octapeptide is around 6 pmol l-1, but that infusions which result in plasma levels of around 25 pmol l-1 produce gallbladder emptying rates comparable with those seen after oral fat. This suggests that the gallbladder is equally sensitive to endogenous and exogenous cholecystokinin and that plasma concentrations observed after oral fat can entirely account for the gallbladder response.     

Inefficacy of gastric emptying procedures

Gastric lavage or ipecac-induced emesis are routinely recommended in the management of the acutely poisoned patient. Efficacy of either procedure has not been shown. Three cases are described clearly demonstrating inefficacy of emesis and wide bore orogastric lavage. The role of these procedures requires careful controlled evaluation. Until the publication of supportive data, their efficacy is unproven.     

Measurement of gastric emptying by standardized real-time ultrasonography in healthy subjects and diabetic patients.

The aim of this study was to simplify and standardize a reproducible, well-tolerated and clinically applicable method for the assessment of gastric emptying rate by real-time ultrasonography. A total of 33 subjects were examined, including 19 healthy subjects and 14 patients with insulin-dependent diabetes mellitus and clinically suspected delayed gastric emptying. Measurements of the gastric antrum were taken in the supine position and in relation to internal landmarks to obtain a standardized cross-sectional image producing the area of a selected slice of the antrum. Diabetic patients were examined on the condition that the fasting blood glucose level was 3.5 to 9.0 mmol/l. Gastric emptying rate was estimated and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after the ingestion of a standardized semisolid breakfast meal (300 g rice pudding, 330 kcal). Interobserver and intraobserver measurement errors were assessed, as was the significance of age and sex on gastric emptying. In comparison to healthy subjects, diabetic patients showed significantly wider median values of the 90 min postprandial antral area, but only a mild tendency toward greater dilation of the gastric antrum prior to and 15 min after meal ingestion. The median value of gastric emptying rate in these diabetic patients was estimated at 29%, which was less than half of that in the healthy subjects (63%). Statistically the difference was highly significant. Interpersonal variability of gastric emptying rate and antral areas was large for both groups. Measurements of gastric emptying rate gave highly reproducible results on separate days and from different observers (interobserver systematic measurement error 0.3% and random measurement error 10.9%; intraobserver systematic measurement error 3.6% and random measurement error 9.5%). No difference in gastric emptying rate was found related to age or sex. We conclude that the use of standardized real-time ultrasonography to determine gastric antral cross-sectional area in a single section of the stomach is a valid method for estimating gastric emptying rate.     

生物电阻抗方法测量液体胃排空的研究

目的:为寻找方便、有效的无损伤胃排空测量手段,尝试建立一种生物电阻抗测量新方法以获取液体胃排空曲线,测量半排空时间.方法:研制了4电极法电阻抗胃排空测量系统,系统由正弦信号发生器、恒流源、电极、前置放大器、解调滤波电路、数据采集单元和上位PC机构成.进行了24例正常人液体胃排空实验,年龄20～21岁.上午空腹,试餐为37℃纯净水400 mL,测量时间约30 min.通过阻抗胃排空曲线计算半排空时间.受试者对实验均知情同意.结果:所有健康志愿者的阻抗胃排空曲线均显示饮水前基础阻抗稳定,在饮水400mL后阻抗急剧升高,然后先快速下降,再缓慢变化,趋近基础阻抗值.24例纯净水胃排空实验的半排空时间均值为(8.78±1.76)min.结论:胃阻抗法虽然受到胃液分泌、试验餐成分等多种因素的影响,但是选用对胃内影响较小、电导率低的非营养性液体可以获得阻抗信号和胃容积变化的对应关系.电阻抗法能实现液体胃排空信号的提取,为临床胃排空功能研究提供一种无创测量的新途径.