Pancreatobiliary responses to an intragastric amino acid meal: comparison to albumin, dextrose, and a maximal cholecystokinin stimulus

Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms.     

Effects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal

Lipid delays gastric emptying, and aging is associated with changes in gastric motor function and transit. However, little is known about the effect of lipid on gastric emptying time in the elderly. To determine the effect of aging on lipid gastric emptying, we used electrical impedance tomography (EIT) to study gastric emptying of liquid meals with or without lipid in five young (23.0 ± 0.6 years, mean ± SEM) and six elderly (73.3 ± 1.6 years) healthy male volunteers. These subjects drank 400 ml of non-lipid soup (triglycerides, 0 g) or lipid soup (triglycerides, 24.6 g) in liquid test meals. To study the effect of lipolysis in the stomach, a liquid test meal containing 240 mg of lipase in the lipid soup was also administered. Plasma cholecystokinin (CCK) concentration was measured by specific radioimmunoassay before and 30 min after the ingestion of a test meal. The gastric emptying time of the lipid soup was longer in the elderly than in the young subjects, and the time was significantly longer for lipid soup than for non-lipid soup (P < 0.05) in both the young and elderly subjects. Gastric emptying time for non-lipid soup was not significantly different between the elderly and young subjects. The administration of lipase shortened the gastric emptying time for lipid in both the elderly and the young subjects. Basal CCK concentration was significantly higher in the elderly than in the young subjects. However, there was no relationship between gastric emptying time and plasma CCK concentration after the ingestion of a test meal in the subjects overall. In conclusion, the delaying effect of lipid on gastric emptying is increased in the elderly, and the administration of lipase accelerates the emptying of lipid from the stomach. Received: October 12, 1998 / Accepted: February 26, 1999     

Effect of aging on plasma cholecystokinin secretion and gallbladder emptying

The present study was undertaken to examine the effect of aging on cholecystokinin (CCK) release, gallbladder emptying and their interrelationships. Therefore, 26 healthy subjects were studied, 13 younger than 40 yr (mean age 31 yr, range 21–39 yr) and 13 older than 40 yr (mean age 64 yr, range 40–78 yr). After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Fasting plasma CCK concentrations were similar in both groups (1.2±0.2 pmol/l in the younger and 1.5 ± 0.3 pmol/l in the older subjects), but the integrated postprandial CCK secretion was significantly (p<0.01) increased in the older subjects (214±21 pmol/l. 60 min) compared to the younger subjects (153±15 pmol/l. 60 min). However, gallbladder emptying was not significantly different between the older and younger subjects (at 60 min 55±7% vs. 61±4%). Gallbladder sensitivity to endogenous CCK was significantly (P<0.02) reduced in the older subjects when compared to the younger subjects. In conclusion, gallbladder sensitivity to CCK is diminished in older subjects but gallbladder emptying remains unchanged due to a significantly increased endogenous CCK secretion.     

Enhanced Release of Cholecystokinin by Soya-Bean Trypsin Inhibitor in Chickens

Whether ingestion of soya-bean trypsin inhibitor (SBTI) alters the release of cholecystokinin (CCK) was investigated in chickens. A meal of an adequate diet supplemented with SBTI (0, 100, or 1000 mg/kg) was given through a stomach tube, followed by CCK determination with specific CCK-8 antibody. The plasma CCK level increased from a basal level (control diet) of 9.6 ± 0.6 to 13.4 ± 0.6 and 18.1 ± 0.8 fmol/ml plasma at 90 min after feeding the diet supplemented with 100 and 1000 mg SBTI, respectively. Since the SBTI supplementation did not affect crop emptying rates significantly, it was concluded that SBTI by itself enhanced CCK release into circulation in a dose-dependent fashion.     

Antihypertensive treatment: Long-term reversal of progression of albuminuria in incipient diabetic nephropathy. A longitudinal study of renal function

This study was undertaken to clarify whether antihypertensive treatment has any effect on the rate of progression of kidney disease in patients with incipient diabetic nephropathy. Six insulin-dependent diabetic men with incipient nephropathy (urinary albumin excretion above 15 μg/min and total protein excretion below 0.5 g/24 h) were first given metoprolol (200 mg daily) with the subsequent addition of hydroflumethiazide. At the start of antihypertensive treatment, mean patient age was 32±4.2 years (SD) and mean duration of diabetes was 18±1.2 years. The patients were followed with repeated measurements of urinary albumin excretion for a mean of 5.4±3.1 years prior to, and for 4.7±1.3 years (SD) during treatment. Mean arterial blood pressure declined significantly during treatment, e.g., the values at 6 months before initiation of treatment being compared with values during the last 6 months of treatment fell from 107 mmHg±7.6 to 93±3.8 (2p=1.5%). Albumin excretion decreased from 131.0 μg/min ×/∇ 2.9 (geometric mean ×/∇ tolerance factor) to 41.7 μg/min ×/∇ 2.9 (2p=1.2%). Albumin clearance in per cent of glomerular filtration rate decreased from a mean of 0.0030±0.0019% (SD) to 0.0011±0.0010% (2p=4.6%). The mean yearly increase in urinary albumin excretion before treatment was 18.0±17.0% (mean±SD); during treatment urinary albumin excretion decreased 19±10% per year (2p=0.7%). No changes were seen in renal plasma flow (516±31.0 ml/min to 520±66 ml/min (n=5)). However, a small but significant fall was seen in glomerular filtration rate (149±6 to 138±10 ml/min, 2p=4.5%, n=5). No significant side effects were seen. Antihypertensive treatment begun at the time of incipient nephropathy may have a more beneficial effect on the progression of disease than when treatment is started during overt nephropathy.     

Gastric emptying and myoelectrical activity in children with nonulcer dyspepsia

We examined the effect of oral cisapride on gastric emptying time and myoelectrical activity using real-time ultrasonography and cutaneous electrogastrography in 10 children with nonulcer dyspepsia. A clear dominant frequency close to 3 cpm was present both at baseline and after eight weeks of cisapride. After cisapride, nine children had an increase in the normal slow wave percentage and the mean percentage of normal slow wave was significantly different (71.90±5.19% vs 79.16±5.54%;P<0.01). Moreover, an increased stability of the dominant frequency, determined by computing the coefficient of variation before and after cisapride, was found (28.12±1.72% vs 23.61±3.47%;P<0.01). At baseline the gastric emptying time, expressed asT1/2, was 139.76±40.04 min and at eight weeks 119.76±30.04 min (P=0.06). As regards the relationship between EGG and gastric emptying, the proportion of children with improved normal slow wave percentage was similar to that with improvedT1/2 emptying (z=0.57,P=0.57). Thus, gastric electrical activity seems to be an important factor in the pathophysiology of nonulcer dyspepsia in children.     

Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia

Summary Patients with early non-insulin-dependent diabetes mellitus (NIDDM) empty glucose solutions from their stomachs more rapidly than non-diabetic control subjects, and this exacerbates postprandial hyperglycaemia.To determine if accelerated gastric emptying occurred in a rat model of NIDDM and influenced postprandial hyperglycaemia, gastric emptying of glucose was measured, and the effect of slowing the gastric emptying rate on postprandial hyperglycaemia was observed. We tested eight male obese Zucker diabetic rats and eight age-matched lean Zucker controls at 10–13 weeks of age to measure gastric emptying of glucose (by gamma scintigraphy). Rats fasted overnight were gavaged with 30 % glucose at 1 ml/100 g body weight. Separately, six Zucker diabetic rats and six lean controls were tested for sensitivity to the inhibitory effects of cholecystokinin and secretin on gastric emptying. The diabetic rats emptied glucose significantly faster than controls (t_1/2 = 37.3 ± 1.5 vs 58.8 ± 2.3 min in controls), and aging exaggerated this differential. Camostat, a stimulant of cholecystokinin and secretin release, added to the glucose meal significantly slowed gastric emptying (t_1/2 = 123 ± 23 and 166 ± 19 min, diabetic vs lean, respectively), and significantly reduced postprandial hyperglycaemia in diabetic rats. Compared to Zucker lean controls, Zucker diabetic rats were as sensitive (cholecystokinin) or more sensitive (secretin) to gastrointestinal hormones that inhibit gastric emptying. The results demonstrate accelerated gastric emptying in a rat model of NIDDM, consistant with similar observations in humans with early NIDDM. These results also support the proposal that interventions to slow gastric emptying may improve glucose control in this disease. [Diabetologia (1997) 40: 136–142] Received: 11 July 1995 and in final revised form: 11 October 1996     

A Synthetic Prostaglandin E2 Analogue,Enprostil, Hastens Gastric Emptying of Solids in Patients with an Active Duodenal Ulcer

The effect of gastric emptying of two doses (35 and 70μg) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 ± 0.38 min^?1· 10^?2 after placebo to 2.77 ± 0.56 min^?1 · 10^?2 after 35 μg enprostil (p < 0.05 versus placebo) and to 3.65 ± 0.64 min^?1 · 10^?2 after 70 μg enprostil (p < 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 ± 6.9% after placebo, 35.2 ± 7.4% after 35 μ enprostil, and 24.1 ± 8.4% after 70 μg enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.     

Effects of Posture on Gastric Emptying, Transpyloric Flow, and Hunger After a Glucose Drink in Healthy Humans

Previous studies suggest that posture has relatively little effect on gastric emptying of high-nutrient liquids; these studies have, however, only assessed overall rates of gastric emptying, whereas gastric emptying is known to be predominantly a pulsatile phenomenon. In healthy subjects perceptions of appetite, such as hunger, are inversely related to antral area and content; hence, changes in intragastric meal distribution induced by posture may affect appetite. Gastric emptying is a major determinant of postprandial glycemia. The aims of this study were to evaluate the effects of posture on patterns of transpyloric flow (TF), gastric emptying (GE), antral area (AA), hunger, and the glycemic response to oral glucose. Eight healthy young subjects (five males, three females; mean age, 24.0 ± 2.4 years; BMI, 21.2 ± 0.6 kg/m²) were studied twice in random order, once in the sitting position and once in the lying (supine) position. After consuming 600 ml water with 75 g glucose, labeled with 20 MBq ^99mTc-sulfur colloid, subjects had simultaneous measurements of (i) TF during consumption of the drink by Doppler ultrasonography, (ii) GE with scintigraphy, (iii) AA at t = −5 and t = 30 min by ultrasonography, and (iv) perceptions of appetite with a visual analogue scale. During drink ingestion TF was greater in the sitting, compared with the lying, position (586 ± 170 vs. 177 ± 65 [cm/sec]×sec; P < 0.05). Posture affected intragastric distribution; more of the drink was retained in the distal stomach in the sitting position (e.g., at 30 min: sitting, 29 ± 3%, vs. lying, 12 ± 3%; P < 0.0001) but had no effect on the overall rate of GE or the blood glucose response. AA at t = 30 min (P < 0.005) was greater in the sitting position; there was an inverse relationship between hunger and AA at 30 min (r = −0.53, P < 0.05). We conclude that posture influences initial TF and intragastric distribution, but not the overall rate of GE of, or the glycemic response to, a large-volume nutrient liquid. The increases in AA and content in the sitting position are associated with a reduction in hunger.     

The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers

Background—Octreotide is used in many centres toprevent complications after pancreatic surgery. Delayed gastricemptying is a another complication occurring in around 30% of patients after pancreatoduodenectomy (PD) and causes prolonged hospital stay.The influence of octreotide on this complication is doubtful.
Aims—To assess the effect of octreotide, at theclinical dosage used after pancreatic surgery, on gastric emptying inhealthy volunteers.
Subjects and methods—Eight healthy malevolunteers (mean age 22.5 years) participated in this double blind,placebo controlled study. On day 1 subjects received 100 µg ofoctreotide or placebo subcutaneously, three times daily and on day 2, one hour after the fourth injection, gastric emptying, postprandialcholecystokinin (CCK) release, and mouth to caecum transit time (MCTT)were measured. This protocol was repeated after one week, in acrossover design. On the test day subjects received a liquid test meal(1.57 MJ/300 ml) and gastric emptying measurements were performed withapplied potential tomography, a non-invasive, validated technique which measures gastric emptying through impedance differences. From thegastric emptying curves, lag time, t₅₀, and postlagemptying rate were measured. MCTT was measured using the hydrogenbreath test.
Results—Lag time decreased from 29.6 (6.3) (mean(SEM)) to 12.2 (4.6) minutes (p<0.05) during octreotide treatment;t₅₀ decreased from 87.8 (12.0) to 47.5 (8.2) minutes(p<0.02) and there was a trend towards an increased postlag emptyingrate (0.8 to 1.6% per minute; p=0.07). MCTT increased from 150 (12.7)to 229 (17.9) minutes during octreotide treatment (p<0.01). Octreotidesuppressed postprandial CCK release (p<0.05).
Conclusions—MCTT was delayed by octreotide,suggesting impairment of small bowel transit. Octreotide administeredat the clinical dosage for pancreatic surgery accelerates gastricemptying, mainly by shortening the lag time. Suppression ofpostprandial CCK release may be involved in this process. Octreotideadministration is therefore not a contributing factor in thepathogenesis of delayed postoperative gastric emptying after PD andmight even play a role in preventing this complication.

     

Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man

Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187±27; mean ±sem) and maximal (>85% of fasting volume) gallbladder contraction (3172±361; AUC) as compared to the other two meals (P<0.05). The mixed and the fat-free meal caused similarly low (<50% of fasting volume) gallbladder contraction (6052±342 and 6134±500, respectively), although they induced markedly different CCK levels (157±12 and 87±13, respectively;P<0.05). Gastric emptying rates were similar for all meals (18,500±3300, 18,600±2700 and 19,800±3100, respectively). The results of this study suggest that CCK plays a major role in the stimulation of gallbladder contraction but that other factors besides CCK are implied when fat-free or low-fat meals are ingested. Furthermore, our findings suggest that a fat intake of 25 g induces maximal gallbladder contraction and may thus prevent an understimulation of gallbladder contraction and the formation of gallbladder stones.     

Effect of cholestyramine and cholecystokinin receptor antagonist CR1505 (loxiglumide) on lower esophageal sphincter pressure in man

Cholecystokinin (CCK) decreases lower esophageal sphincter pressure (LESP) in man. Cholestyramine, a nonabsorbable bile salt binding resin, stimulates endogenous CCK secretion. We have investigated the effect of oral ingestion of 16 g cholestyramine without and with infusion of the CCK receptor antagonist CR1505 (loxiglumide, 15 mg/kg/90 min) on LESP in seven healthy subjects. LESP was recorded for 90 min, in 10-min intervals, with the pull-through technique using a four-lumen water-perfused catheter. Oral ingestion of cholestyramine resulted in a significant (P<0.05) decrease in LESP, starting from 10 min and continuing during the entire experiment (basal LESP: 11.8±2 mm Hg, minimal value reached during cholestyramine: 7.3±1 mm Hg;P<0.05). Pretreatment with loxiglumide completely antagonized the effect of cholestyramine on LESP. Infusion of loxiglumide without cholestyramine did not affect basal LESP. It is concluded that: (1) cholestyramine significantly reduces LESP; (2) this reduction in LESP does not occur after pretreatment with loxiglumide, indicating that cholestyramine influences LESP through CCK release; and (3) basal LESP is not regulated by CCK.     

Gallbladder emptying,plasma levels of estradiol and progesterone,and cholecystokinin secretion in liver cirrhosis

Defective gallbladder emptying has been proposed as a possible accessory pathogenetic factor to explain the increased prevalence of gallstones in liver cirrhosis. In this study we have evaluated the fasting volume and the meal-stimulated emptying of the gallbladder, the plasma levels of estradiol and progesterone, and the basal and postprandial secretion of cholecystokinin in Child A cirrhotic patients compared to normal subjects. Basal (42.2±27 vs 22.8±8.4 ml) (P<0.002) and residual (8.4±8.7 vs 4.6±3.8 ml) (P<0.05) gallbladder volumes were higher in cirrhotics but neither the integrated gallbladder response to meal nor the maximal percentage of emptying was significantly different. Circulating estradiol and progesterone was slightly increased in only 1/13 and 5/13 cirrhotics, respectively. In eight cirrhotics and seven normals taken from the overall populations, the secretion of cholecystokinin was also measured. The fasting plasma level of cholecystokinin was higher in the cirrhotics (6.71±5.08 vs 2.02±0.46 pmol/liter) (P<0.01). The meal-stimulated integrated plasma cholecystokinin response also was greater in cirrhotics (438.5±615 pmol/liter/270 min) than in normals (153±170.4 pmol/liter/270 min), but this difference was not significant because of the small study population. In spite of a normal kinetics of postprandial emptying, cirrhotic patients show increased fasting gallbladder volume and increased plasma levels of basal and postprandial cholecystokinin. Circulating estradiol and progesterone do not seem to be responsible for the large gallbladder volume found in liver cirrhosis.     

Regional myocardial lidocaine concentration following continuous intravenous infusion early and late after myocardial infarction

The regional concentration of lidocaine using a double constant infusion technique (250 μg/kg/min × 15 minutes followed by 35 μg/kg/mg/min × 120 minutes) was studied immediately (2 hours) in seven dogs and 24 hours (six dogs) after myocardial infarction. Tissue levels were determined by gas chromatography and related to regional myocardial blood flow as determined by the radioactive microsphere technique in multiple samples. At 2 hours after infarction a significantly higher lidocaine concentration (4.1 ± 0.42 μg/g) was found in zones with greatly reduced blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that (2.6 ± 0.19 μg/g) in zones with normal blood flow (regional myocardial blood flow greater than 0.8 ml/min per g) (p < 0.01). In contrast, in the 24 hour model the opposite situation was observed. Although the concentration of lidocaine in the infarct zone was substantial, a significant decline in lidocaine tissue concentration was found in the zones of lowest blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that in normal zones (1.76 ± 0.21 versus 3.38 ± 0.21 μg/g, p < 0.001). In addition, no significant differences in lidocaine concentrations were found between endocardium and epicardium in any of the groups other than those related to regional myocardial blood flow.Thus, with the double constant infusion technique, lidocaine reached normal and ischemic myocardium in concentrations equivalent to therapeutic plasma concentrations, even in lower infarct blood flow zones, with no significant differences between endocardium and epicardium. Of perhaps greater significance, the age of the ischemic insult is an important determinant of lidocaine tissue distribution in infarcted myocardium.     

The Effect of Vagal Stimulation on the Release of Cholecystokinin in Anaesthetized Pigs

The effect of electrical vagal stimulation on the release of cholecystokinin (CCK) was studied in nine anaesthetized pigs. Plasma CCK concentrations were measured radioimmunologically by means of an antiserum specific for the sulphated tyrosine region of CCK. Stimulation of both vagal nerves for 10 min induced an increase in CCK concentrations from 1.9 ± 0.4pmol/l to a peak value of 3.6 ± 0.4pmol/l in portal vein plasma and from 1.5 ± 0.3 to 2.7 ± 0.4pmol/l in arterial plasma. Mean integrated increments during stimulation were 12.0 ± 2.5 pmol/1/10 min (p < 0.01) and 8.3 ± 1.0 pmol/1/10 min (p < 0.001), respectively. The results suggest a vagal innervation of the CCK cell in the upper small intestine.     

Gastric Emptying, CCK Release, and Satiety in Weight-Stable Obese Subjects

Scintigraphic gastric emptying studies are far from conclusive in obesity. The aim was to investigate gastric emptying and CCK release in weight-stable obese subjects on their usual diet and to study the impact of factors known to determine gastric emptying. Patients entering a weight reduction program were asked to participate in a study examining gastric emptying by scintigraphy and CCK release in response to a meal with questionnaires on feelings of satiety. Forty-five patients (9 M, 36 F) with a mean (SD) BMI of 37.0 (4.0) kg/m² entered the study. The mean T₅₀ (emptying of 50%) of fluids was 20.7 (10.3) min, and that of solids 141.9 (168.3) min. The percentage emptying of solids was 34.5 (19.9)%/hr. CCK values peaked within 42 min and paralleled the subjective ratings of satiety but did not correlate with gastric emptying. Five of 45 subjects (11%) had very prolonged gastric emptying of solids; they showed higher caloric intakes and higher insulin levels. They did not differ in CCK values and ratings of satiety but scored higher in being active and awake. Without these five subjects the T₅₀ of solids was 94.3 (36.1) min, and the percentage of emptying 37.9 (18.4)%/hr. Liquid emptying was faster and solid emptying similar compared with those of normal-weight individuals. Height, fat-free mass, and waist–hip circumference were positively related to solid emptying. In weight-stable obese subjects liquid emptying was faster and solid emptying similar to those in normal-weight subjects. Higher caloric intakes and insulin levels were present in subjects with prolonged solid emptying; they also appeared more vigilant. Body size and composition were the only determinants suggesting a faster solid emptying in taller and muscular subjects or in subjects with more intraabdominal fat.     

Cimetidine effect on dopaminergic modulation of prolactin release in healthy women

The aim of the present study was to test whether cimetidine (Cim) influences PIF (prolactin inhibitory factor), and thereby indirectly affects the release of prolactin (PRL) from the pituitary lactotrophs. For that purpose 10 mg metoclopramide (Met), known for its dopamine-receptor blocking properties, were first given orally to 6 subjects. This raised the PRL level from 13 ± 2 to 97 ± 12 ng/ml in 60 min (p < 0.001). PRL tended to plateau at this level until 120 min. An additional 7 subjects were then injected iv with 400 mg Cim, 90 min after oral administration of placebo. Placebo did not change the basal PRL level, but the subsequent Cim injection raised the PRL level from 14 ± 4 to 66 ± 9 ng/ml (p < 0.01). When, in the same subjects, an oral dose of Met was given (10 mg) PRL increased from 19 ± 4 to 112 ± 10 ng/ml (p < 0.001). A subsequent Cim injection, given on top of the PRL plateau, 90 min after the Met ingestion, however, failed to induce any further increase in PRL. To exclude that this failure was not merely a reflection of a Met-induced depletion of the PRL stores, 25 μg thyrotropin-releasing hormone (TRH) were given iv to an additional 6 subjects, 90 min after ingestion of either placebo or Met. Also in these subjects placebo left basal PRL unaffected. The subsequent TRH injection, however, raised PRL from 10 ± 2 to 55 ± 6 ng/ml (p < 0.001). Met increased PRL from 17 ± 4 to 133 ± 19 ng/ml (p < 0.01) in these subjects, and TRH, subsequently injected, induced a further PRL increase to 174 ± 18 ng/ml (p < 0.01). The observation that Cim fails to elicit an increase in PRL after priming with Met thus indicates that Cim, under normal conditions, stimulates the PRL release via a reduced dopaminergic inhibition of the lactotrophs.     

The effect of duodenumpreserving resection of the head of the pancreas on basal and stimulated insulin, glucagon, pancreatic polypeptide, and cholecystokinin levels in dogs

Several major pancreatic resections have been proven effective for the relief of pain caused by chronic pancreatitis. Distinct morbidity, however, and interference with gastrointestinal hormone response patterns have been documented. We have tested the effect of the duodenumpreserving resection of the head of the pancreas on basal and meal-stimulated (TMA) blood glucose and plasma insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin levels (CCK) in dogs(n =9). Intravenous glucose tolerance tests (IVGTT) were performed in addition. Tests were performed before and at six and 12 wk after operation. Results of TMA were expressed in basal and integrated levels for glucose, insulin and glucagon. PP and CCK responses were expressed in incremental levels, results of IVGTT as K-values and integrated insulin response. Basal glucagon, insulin, and PP levels (mean ± SEM) decreased from 86 ± 23 to 44 ± 10 pg/mL, from 14 ± 3 to 8±1 μU/mL, and from 75 ±11 to 24±3 pM, respectively (p<.05), basal CCK values were not affected. Incremental PP response decreased from 363 ±39 to 10±4 pM at 12 wk. Incremental CCK, integrated insulin, and glucagon values showed no significant changes. K-values dropped from 3.5 ±0.3 to 1.5 ±0.2 at six weeks, and glucose-induced integrated insulin from 1488 ±235 to 701 ± 108. All parameters measured stabilized as of six weeks after operation. It is concluded that duodenumpreserving resection of the pancreatic head leads to vagal denervation of the pancreas and accelerated gastric emptying. Probably as a result of the unaffected CCK response, no quantitative changes in integrated insulin and glucagon response were observed after operation. The decrease in glucose tolerance may be caused by a combination of decreased islet-mass and qualitative changes in insulin delivery, as a result of distinctive histological changes after ductal injection with Tissucol.     

Reduced myocardial blood flow resulting from dynamic changes in coronary artery stenosis

To evaluate the interaction of coronary vasomotor tone and stenosis, we studied the effects of ergonovine and adenosine on partially obstructed coronary arteries in 6 closed chest dogs. Coronary stenosis was created by partially inflating a balloon catheter with a distal lumen in the left anterior descending or circumflex coronary artery. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow measured with 15 micron radioactive microspheres. Coronary artery vasoconstriction, induced by ergonovine (0.6 mg i.v.), caused a small, but nonsignificant, increase in stenotic resistance (1.42 ± 0.25 to 2.68 ± 0.64 mm Hg/ml per min) and had no effect on myocardial blood flow. Coronary arteriolar dilation induced by adenosine increased stenotic resistance (1.52 ± 0.25 to 9.01 ± 2.49 mm Hg/ml per min, P < 0.05) and the pressure gradient across the stenosis (18.8 ± 3.0 to 41.3 ± 7.5 mm Hg, P < 0.05). Adenosine increased myocardial blood flow from 0.52 ± 0.05 ml/min per g to 1.43 ± 0.20 ml/min per g (P < 0.05) in the regions supplied by unstenosed arteries, while in the region perfused by the stenosed artery blood flow fell from 0.51 ± 0.06 to 0.29 ± 0.13 ml/min per g (P < 0.05), with the endocardium most severely affected (0.55 ± 0.04 ml/min per g to 0.26 ± 0.09 ml/min per g, P < 0.05).Thus changes in severity of stenosis produced by altered coronary pressure and flow can influence blood flow to the myocardium. Such dynamic changes in coronary artery stenosis may be important in the pathogenesis of angina and myocardial infarction.     

Cold pain prolongs gastric emptying of liquid but not solid meal: an electrical impedance tomography (EIT) study

Stressful stimuli are reported to affect gastric emptying. However, methods for measuring gastric emptying are, in themselves, stressful. Electrical impedance tomography (EIT) is a method for measuring gastric emptying noninvasively. We used EIT to measure gastric emptying of liquid and solid meals to determine the effect of cold pain stress on gastric emptying. EIT (DAS-01P APT system; University of Sheffield, UK) was carried out in six healthy women (age, 21.6 ± 0.4 [mean ± SD] years) who had ingested a liquid (potage, 263 g; 139 kcal) or solid (beef patty, 205 g; 435 kcal) test meal. Cold pain stimuli consisted of repeated immersions of the subject's non-dominant hand into ice water (4°C) for 1 min, with a 15-s recovery period between immersions, for a total of 20 min. For the control stimulus, water at 37°C was used. The cold pain stimulus was applied immediately after the ingestion of a test meal. All studies were carried out randomly in each subject at intervals of more than 1 week. With cold pain, the half emptying time of the liquid meal was significantly greater than that with the control stimulus (47.6 ± 26.1 min vs 28.1 ± 10.8 min, P < 0.05). For the solid meal, the half emptying time did not differ between stimuli (101.9 ± 44.8 min with cold pain vs 92.6 ± 30.5 min with control stimulus). There were no significant differences in lag time between the liquid and solid meals. Cold pain stress delayed gastric emptying of liquid but not solid meals. Received: September 28, 1999 / Accepted: February 25, 2000