Effect of solid meal on gastric emptying of,and glycemic and cardiovascular responses to,liquid glucose in older subjects

Gastric emptying is a determinant of the postprandial glycemic and cardiovascular responses to oral carbohydrate. We evaluated the effects of a solid meal on gastric emptying and the glycemic and cardiovascular responses to oral glucose in healthy older subjects. Ten subjects aged 72.1 +/- 1.9 yr were studied. Each subject had measurements of gastric emptying, blood glucose, serum insulin, blood pressure, and heart rate after ingestion of a 50-g glucose drink (300 ml) with (mixed meal) or without (liquid only) a solid meal (300 g ground beef). Gastric emptying of liquid was initially slightly more rapid (P < 0.05) after the mixed meal compared with liquid only at 5 min (92.0 +/- 1.5 vs. 96.0 +/- 1.3%) and much slower (P < 0.05) after 120 min. The time to peak blood glucose was less (39.0 +/- 4.0 vs. 67.5 +/- 10.3 min; P < 0.01) and blood glucose subsequently lower (P < 0.01) after the mixed meal. The increase in serum insulin was greater (P < 0.001) after the mixed meal. Blood pressure fell (P < 0.05) in the first 30 min, with no difference between the two meals. Increase in heart rate after both meals (P < 0.005), was greater (P < 0.05) after the mixed meal. The presence of a noncarbohydrate solid meal had discrepant effects on early and subsequent emptying of a nutrient liquid, which affects postprandial glycemia and increased heart rate.     

Relationship of gastric emptying and volume changes after a solid meal in humans

Noninvasive imaging has been developed to measure gastric volumes. The relationship between gastric emptying and volume postprandially is unclear. The aims were to 1) develop a 3-dimensional (3D) single photon emission-computed tomography (SPECT) method to simultaneously measure gastric volume and emptying postprandially, 2) describe the course of gastric volume change during emptying of the meal, and 3) assess a 3D method measuring gastric emptying. In 30 healthy volunteers, we used (111)In-planar and (99m)Tc-SPECT imaging to estimate gastric emptying and volume after a radiolabeled meal. A customized analysis program of SPECT imaging assessed gastric emptying. A Bland-Altman plot assessed the performance of the new SPECT analysis compared with planar analysis. Gastric volume postprandially exceeds the fasting volume plus meal volume. The course of volume change and gastric emptying differ over time. Higher differences in volumes exist relative to fasting plus residual meal volumes at 15 min (median 763 vs. 568 ml, respectively, P < 0.001), 1 h (median 632 vs. 524 ml, P < 0.001), and 2 h (median 518 vs. 428 ml, P < 0.02), in contrast to similar volumes at 3 h (median 320 vs. 314 ml, P = 0.85). Analysis of SPECT imaging accurately measures gastric emptying compared with planar imaging with median differences of 1% (IQR -2.25 to 2.0) at 1 h, 1% (-3.25 to 2.25) at 2 h, and -2.5% (-4 to 0) at 3 h. Gastric volume exceeds meal volume during the first 2 postprandial hours, and simultaneous measurements of gastric volume and emptying can be achieved with a novel 3D SPECT method.     

The effect of macronutrients on gastric volume responses and gastric emptying in humans: A magnetic resonance imaging study

The effects of macronutrients on gastric volume changes, emptying, and gastrointestinal symptoms are incompletely understood. Three liquid meals of 500 ml (fat emulsion, 375 kcal; protein solution, 375 kcal; glucose solution, 400 kcal) were infused into the stomach of 12 healthy volunteers on three occasions. Studies were performed in seated body position using an open-configuration magnetic resonance imaging (MRI) system. MRI imaging sequences, assessing stomach and meal volumes, were performed prior to and at times t = 0, 3, 6, 9, 12, 15, 25, 35, 45, 60, 75, and 90 min after meal administration. Areas under the curve for the early emptying phase (0-15 and 0-45 min) were calculated, and characteristics of the volume curves were analyzed by a gastric emptying model. Gastrointestinal symptoms were assessed by a self-report scale. Initial (t = 0 min) and early postprandial gastric volumes were highest for glucose because of lower initial emptying. However, in the early emptying phase the characteristics of the volume curves for stomach and meal were uniform for all macronutrients. Perceptions of fullness and satiety were linearly associated with postprandial gastric volumes, but not with macronutrient composition. Isovolumic macronutrient meals modulate gastric volume response by initial meal emptying patterns. Macronutrient specific accommodation responses, as shown in barostat studies, are not reflected as gastric volume responses under noninvasive conditions.     

Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans

Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying. The interrelationships between volume, emptying, and postprandial symptoms in response to GLP-1 are unclear. We performed, in healthy human volunteers, a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using (99m)Tc-single photon emission computed tomography imaging, gastric emptying of a nutrient liquid meal (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and retarded gastric emptying; MTV and postprandial symptoms were not different compared with controls. Effects on postprandial gastric function were associated with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms despite significant inhibition of gastric emptying and vagal function; this may be partly explained by the increase in postprandial gastric volume.     

Assessment of antral grinding of a model solid meal with echo-planar imaging

Mathematical modeling of how physical factors alter gastric emptying is limited by lack of precise measures of the forces exerted on gastric contents. We have produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2) was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22 +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N. With the HV meal, emptying of the harder beads was accelerated. The sense of fullness after ingesting the LV meal correlated linearly (correlation coefficient = 0.99) with gastric volume and was independently increased by the harder beads, which were associated with an increased antral diameter. We conclude that the maximum force exerted by the gastric antrum is close to 0.65 N and that gastric sieving is impaired by HV meals.     

Influence of sildenafil on gastric sensorimotor function in humans

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo (n = 13) or sildenafil, 50 mg (n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 +/- 15 vs. 163 +/- 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 +/- 38 vs. 253 +/- 42 ml, P < 0.05) or 60 min (348 +/- 49 vs. 247 +/- 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 +/- 4 vs. 56 +/- 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.     

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.     

Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction

Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories.     

Cholecystokinin pathways modulate sensations induced by gastric distension in humans

Ingested fat releases CCK, causes gastric relaxation, delays gastric emptying, and limits meal size; however, the mechanistic link among these actions has not been established. Fatty acid release of CCK is chain-length sensitive; dodecanoic acid (C12) induces greater CCK release than decanoic acid (C10). The effect of C12 or C10 on tolerance to subsequent intragastric infusion of liquid was determined in healthy subjects, with and without the CCK(1) receptor antagonist dexloxiglumide. Gastric wall relaxation after either fatty acid was assessed by graded volume distension and by barostat; gastric emptying was measured by gastric aspiration and by a [(13)C]octanoic acid breath technique. C12 released more CCK (mean plasma CCK after vehicle, 4.7 +/- 0.8 pM; C10, 4.8 +/- 0.3 pM; C12, 8 +/- 1.2 pM; P < 0.05 C12 vs. C10 or vehicle) and reduced the volume of water (and of 5 and 25% glucose solutions) delivered at maximum tolerance compared with C10 or vehicle (volume of water tolerated after vehicle, 1,535 +/- 164 ml; C10, 1,335 +/- 160 ml; C12, 842 +/- 103 ml; P < 0.05 C12 vs. C10 or vehicle); this effect was abolished by dexloxiglumide. Intragastric volumes were always similar at the limit of tolerance, and, whereas gastric relaxation occurred to similar degrees after the fatty acids, its duration was longer after C12, which also induced a longer delay in half-gastric emptying [t(1/2)(min) after vehicle, 53 +/- 2; C10, 67 +/- 3; C12, 88 +/- 7; P < 0.05 C12 vs. C10 or vehicle]. In conclusion, ingestion of a CCK-releasing fatty acid reduces the tolerated volume of liquid delivered into the stomach, primarily via a CCK(1) receptor-mediated delay in gastric emptying.     

Some observations of the effects of body weight, temperature, meal size and quality on gastric emptying time in the turbot, Scophthalmus maximus (L.) using radiography

The gastric emptying time (G.E.T.) in turbot was investigated using X-radiography and was found to decrease with temperature. Small fish processed a given ration, expressed as percent body weight, faster than large fish (G.E.T. was found to be proportional to (fish weight)^0.364). Large meals in a given fish were processed at a faster rate than small meals. Gastric emptying rate (G.E.R.) was found to be proportional to (meal size g)^0.613 at 8° C and (meal size g)^0.788 at 19° C. These exponents are in agreement with a recently proposed model relating G.E.T. and G.E.R. to meal size (Fänge & Grove, 1978). Large fish emptied a meal of given absolute size from the stomach at a faster rate (g h⁻¹) than small fish. Experimental meals diluted with kaolin were evacuated in significantly less time than a control diet, suggesting that turbot may adjust feeding rates when food quality varies.     

Gastric accommodation and motility are influenced by the barostat device: Assessment with magnetic resonance imaging

The barostat is considered the gold standard for evaluation of proximal gastric motility especially for the accommodation response to a meal. The procedure is invasive because it involves the introduction of an intragastric catheter and bag and is not always well tolerated. Moreover, the barostat bag itself may influence motility. Nowadays magnetic resonance imaging (MRI) is able to measure several aspects of gastric motility noninvasively. To evaluate whether the accommodation response of the stomach, observed with the barostat, is present during MRI and whether the barostat interferes with gastric physiology, gastric accommodation, motility, and emptying were studied twice in 14 healthy subjects with MRI using three-dimensional volume scans and two-dimensional dynamic scans once in the presence of a barostat bag and once when the barostat bag was not present. Fasting and postprandial intragastric volumes were significantly higher in the experiment with barostat vs. without barostat (fasting: 350 +/- 132 ml vs. 37 +/- 21 ml, P < 0.0001; postprandial: 852 +/- 126 ml vs. 361 +/- 62 ml, P < 0.0001). No significant differences were found in gastric emptying (88 +/- 41 vs. 97 +/- 40 ml/h, not significant) and contraction frequency between both experiments. The accommodation response observed in the presence of the barostat bag was not observed in the absence of the barostat bag. In conclusion, the presence of an intragastric barostat bag does not interfere with gastric emptying or motility, but the accommodation response measured with the barostat in situ is not observed without the barostat bag in situ. Gastric accommodation is a nonphysiological barostat-induced phenomenon.     

The amount of food ingested in a single meal by rainbow trout offered chopped herring, dry and wet diets

Two-year-old 1·5-kg rainbow trout were held in cages and conditioned by feeding either on low-fat chopped herring (H trout) or dry pellets (P trout) for 15 weeks. Their satiation amounts were then determined under standard conditions. On a wet weight basis H trout ate 2·5-3·5 times more food than P trout; this was sufficient to compensate for the high water content of herring and thereby maintain the dry matter intake. When P trout were offered herring (PH trout) they consumed more food than when offered dry pellets but not as much as H trout. Stomach capacity restricted the intake and their dry matter intake was reduced by c. 40%. When H trout were offered dry pellets (HP trout) they adjusted their intake immediately close to the level of P trout although their larger stomachs could have accommodated more than twice this volume of dry food. The return of appetite after a satiation meal was almost linear with time. Appetite increased at c. 556 mg g^-1 body weight h^-1 for H trout and at 142 mg g^-1 bw h^-1 for P trout. The return of appetite in PH trout was significantly slower (c. 370 mg g^-1 bw h^-1) than in H trout; the previous dietary history of the PH trout limited their capacity to process larger volumes of wet food in a single meal. Fish offered dry diet (P and HP trout) had similar rates of appetite return despite their previous feeding history suggesting that the property of the dry feed itself might limit meal size. The total gastric emptying time of diets of similar dry matter content (with and without large amounts of water) was similar, but the delay time before gastric emptying starts tended to be longer for dry diets. Dry pellets appear to impose a demand for water that prolongs the gastric delay. This water demand is met partly by drinking since the trout fed on dry pellets drank significantly more (436 ± 189 mg kg^-1 h^-1) than unfed and herring-fed trout which drank little or not at all (65 ± 113 and 70 ± 66 mg kg^-1 h^-1 respectively). Dietary water facilitated food processing and increased daily dry matter intake of trout when fed four times a day. When only one satiation meal per day was allowed, dietary water had no effect. It is concluded from this work that, in addition to gastric volume, a short-term limitation on the size of satiation meals in the rainbow trout is the availability of water to moisturize the food and thus to promote gastric digestion and emptying.     

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.     

Effect of intragastric barostat bag on proximal and distal gastric accommodation in response to liquid meal

The barostat is the gold standard for measurement of proximal gastric accommodation. Ultrasonography can be used to measure gastric volume. The aim was to investigate the effects of the barostat bag on gastric accommodation and transpyloric flow. Accommodation after a liquid meal (300 ml, 450 kcal) was measured twice at random in eight healthy volunteers. Proximal accommodation was measured once using barostat and once using ultrasound (US). Antrum accommodation was measured using US. Bag volume (BV), antral area (AA), proximal gastric area, and proximal gastric diameter (PGD) data were assessed before and 1, 5, 15, 30, 40, 50, and 60 min postprandially. Transpyloric flow was measured using Doppler 1-5 min postprandially. Fasted, AA size was not affected by the barostat bag (1 mmHg > minimal distension pressure; 2.7 +/- 0.5 vs. 2.6 +/- 0.3 cm(2)). Postprandially, AAs were larger with the bag present (ANOVA, P < 0.04). Maximum AA was reached with the bag in 5 min, without the bag in 1 min postprandially (15.1 +/- 2.3 vs. 9.4 +/- 1.5 cm(2); P < 0.03). Furthermore, AAs were related to BVs (r = 0.57; P < 0.01). After bag deflation, AA decreased (11.9 +/- 1.8 to 7.0 +/- 0.9 cm(2); P = 0.02) and was comparable with the 60-min AA size without the bag (7.1 +/- 1.2 cm(2); P = 0.76) present. Proximal gastric radius calculated from the BVs and PGDs was larger with the bag present (ANOVA, P < 0.001). No effect on early gastric emptying was observed. Postprandially, the barostat bag causes dilatation of the antrum due to meal displacement without influencing early gastric emptying. This antral dilatation is likely to induce exaggerated proximal gastric relaxation observed in studies using the barostat to evaluate fundic accommodation.     

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.     

Meal occurrence in Japanese quail in relation to particle size and nutrient density

Japanese quail ate shorter meals with pellets than with mash, and longer and more frequent meals with diluted mash (40% cellulose) than undiluted mash. The differences with particle size were due to different rates of ingestion, and those with nutrient density to different meal volumes and different rates of passage. Average meal size was about the same with all foods in terms of weight eaten, but not nutrients digested. Short-term adjustments in feeding were concerned mainly with changes in meal frequency, and longer-term adjustments mainly with changes in meal size. It is concluded that the control of meal-eating is concerned with emptying and filling of the digestive tract and not with changing levels of circulating nutrients, and parts of the gut that may be involved are suggested.     

Modulation of gastric motor activity by a centrally acting stimulus, circular vection, in humans

The aims of this study were to investigate gastric motor correlates of vection, a centrally acting stimulus, and relate these responses to the induction of motion sickness symptoms. Antral contractile activity and gastric volume retained after a liquid nutrient meal (600 ml) were assessed by magnetic resonance imaging in healthy subjects during two different protocols. Vection was induced by an optokinetic drum, and subjects repeatedly rated the intensity of vection and nausea on 0-10 analog scales. Vection delayed gastric emptying [99% (89-102%) [median (interquartile ranges)] of volume retained at 28 min; control situation: 79% (69-81%), P < 0.05]. Antral contractile activity followed a distinct time course of rapid decrease [-64% (-72 to -59%) change from baseline activity] immediately after onset of drum rotation followed by gradual recovery upon withdrawal of the stimulus. No relationship was found between the severity of nausea and inhibition of gastric emptying or antral contractile activity. The inhibition of antral contractile activity appears to be a good measure of the peripheral response to vection but is probably independent of subjective symptom induction.     

Influence of enkephalinase inhibitors on gastric emptying in mice depends on the nature of the meal

The effects of two enkephalinase inhibitors (thiorphan and acétorphan) and DALAMIDE on gastric emptying of fat or non-fat meals were evaluated in mice. When administered intraperitonally at low doses (0.1 and 0.2 mg/kg) 30 min prior to a fatty (milk) meal, both thiorphan and acetorphan increased significantly (P less than 0.01) gastric emptying; these effects were maximal for 0.2 and 0.1 mg/kg respectively and decreased progressively to be not significant for doses higher than 5 mg/kg for thiorphan and 0.5 mg/kg for acetorphan. Similarly DALAMIDE given IP increased significantly (P less than 0.05) gastric emptying at doses of 0.5 and 1 mg/kg while a slowing of gastric emptying was obtained for 10 times higher doses. The effects of thiorphan (0.2 mg/kg) and DALAMIDE (0.5 mg/kg) were blocked by previous administration of naloxone (0.3 mg/kg) and methyl-naloxone (0.5 mg/kg) while only naloxone (0.3 mg/kg) blocked the slowing effect of high dose of DALAMIDE. Administered prior to a non-fat meal, thiorphan (1 mg/kg) stimulated gastric emptying and inhibited it at higher dosage (10 mg/kg). Neither acetorphan nor DALAMIDE at similar dosages affected the gastric emptying of a non-fat meal and the effects of thiorphan (1 and 0.1 mg/kg) were not blocked by naloxone (0.3 mg/kg). It is concluded that enkephalinase inhibitors (thiorphan and acetorphan) administered systemically stimulate the gastric emptying of a fat meal by increasing enkephalin levels in peripheral tissues, while thiorphan exhibits non-opiate effects on gastric emptying of a non-fat meal.     

Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution (n = 6 each group). Final plasma viscosities were 1.4 +/- 0.2, 2.2 +/- 0.1, and 2.7 +/- 0.2 cp, respectively, (P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 +/- 0.2, 2.9 +/- 0.4, and 3.9 +/- 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 +/- 16%, whereas the two high-viscosity solutions were 71 +/- 15% and 76 +/- 12% (P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po(2) was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po(2) showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline (P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher (P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.     

5-Hydroxytryptophan modulates postprandial motor patterns of canine proximal small intestine

The aim of the study was to clarify whether 5-hydroxytryptophan (5-HTP) stimulates the postprandial motor pattern of the duodenum in a similar way as that of the adjacent jejunal segment in dogs. Computerized analysis of motor patterns recorded by closely spaced strain gauges focused on the temporal and spatial distribution of the contractions. Results indicate that 5-HTP increased the incidence and the length of the spread of contraction waves after both an acaloric and a nutrient meal in the duodenum as well as in the adjacent jejunal segment. Effects were more pronounced after the nutrient than after the acaloric meal. After the nutrient meal, but not after the acaloric meal, 5-HTP additionally enhanced the number of both duodenal and jejunal contractions per minute and increased the force of duodenal contractions. The acaloric meal induced significant differences in the motor patterns between the duodenum and the adjacent jejunum. 5-HTP abolished these differences owing to a relatively stronger stimulation of duodenal motility. 5-HTP did not affect gastric emptying of both meals. We conclude (i) that 5-HTP is a potent stimulator of propagated contractions both in the duodenum and the adjacent jejunal segment and (ii) that intestinal motor patterns can be regulated independently of gastric emptying.