Cholecystokinin octapeptide increases rectal sensitivity to pain in healthy subjects

Hypersensitivity during rectal distension has been demonstrated in irritable bowel syndrome (IBS). Studies performed in animals and indirect data in humans suggest that cholecystokinin (CCK) could modulate visceral sensations. The aim of this study was to assess the effects of i.v. infused sulphated cholecystokinin octapeptide (CCK-OP) on rectal sensitivity in response to distension. In eight healthy subjects, rectal sensitivity and compliance were determined during a randomized double-blind study, with four sessions each separated by 7 days. Sensory thresholds and rectal compliance were assessed during slow-ramp (40 mL min-1) and rapid-phasic distensions (40 mL s-1, 5 mmHg stepwise, 1-min duration), and were compared before and during continuous infusion of either saline or CCK-OP at 5, or 20 or 40 ng kg-1 h-1. During rapid phasic distension but not during slow ramp distension, CCK-OP at 40 ng kg-1 h-1 produced a significant decrease in sensory thresholds compared with the basal period. Rectal compliance was not modified by any infusion. At pharmacological doses, CCK-OP decreases sensory thresholds during rapid phasic distension that may preferentially stimulate serosal mechanoreceptors, but has no effect on mucosal mechanoreceptors stimulated during slow ramp distensions. Modulation of rectal sensitivity by CCK could be implicated in the pathogenesis of the rectal hypersensitivity observed in IBS.     

Influence of age on rectal tone and sensitivity to distension in healthy subjects

Hypersensitivity to rectal distension is frequently observed in patients with irritable bowel syndrome (IBS). However, few data are available about the influence of age on rectal sensory thresholds and tone. The aim of this study was to measure rectal sensory thresholds and tone with a barostat in 12 healthy subjects (aged 86 +/- 4 years, eight females, four males) as compared with 12 young healthy male controls (26 +/- 1 years). Isobaric phasic distensions were performed in the fasted state (increment of 4 mmHg, steps of 5 min, interval of 5 min). Rectal tone changes were then measured as changes in volume of the barostat bag, the pressure being kept constant. After a baseline recording of 1 h, a 1000-kcal meal was served and the tone recorded until return to baseline. Rectal sensory thresholds were significantly higher in aged subjects. First sensation, sensation of urge to defaecate and sensation of pain were triggered at 21.1 +/- 3.2 mmHg, 30.4 +/- 5.4 mmHg and 40.5 +/- 5.0 mmHg, respectively, in aged subjects, vs 13.3 +/- 4.6 mmHg (P < 0.05), 20.7 +/- 1.0 mmHg (P < 0.001) 31.3 +/- 1.7 mmHg (P < 0.001) in controls. Rectal compliance was not significantly different between the two groups. Mean barostat bag volume was 104 +/- 13 mL in fasting aged subjects and 125 +/- 23 mL in controls (NS). After the meal, the barostat bag volume decreased by 69 +/- 11% during 85 +/- 17 min in aged subjects and 75 +/- 14% during 89 +/- 15 min in young controls (NS). Rectal sensory thresholds triggered by distension are increased in aged healthy subjects while compliance and tone are not different. Age should be considered as a confounding factor when studying rectal sensitivity and further studies in aged patients with IBS should include a group of control subjects within the same range of age as studied patients.     

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.     

A disturbance of gastric function in bulimia nervosa.

BACKGROUND: Because the stomach plays an important role in the development of satiety, gastric function was examined in bulimia nervosa (BN). METHODS: Sixteen patients with BN and 16 controls swallowed an inflatable bag, which was positioned in the proximal stomach. Minimal distending pressure (MDP), the pressure needed to overcome intraabdominal pressure, was determined. Gastric volume was recorded after subjects drank a liquid meal. RESULTS: MDP was similar in patient and control groups (7.56 +/- 2.13 vs. 7.13 +/- 2.06 mmHg; t =.57, df = 30, p =.58). Average postmeal gastric relaxation was significantly lower in the patient group (29.7 +/- 97.8 vs. 105.1 +/- 103.3 mL; t = 2.13, df = 30, p =.042). CONCLUSIONS: Stomach relaxation following food consumption is significantly diminished in patients with BN. Physiologic abnormalities of stomach function in BN may contribute to the perpetuation of disturbances in behavior in this disorder.     

The effect of glucagon-induced gastric relaxation on TLOSR frequency

This study aimed to determine the effect of glucagon-induced gastric relaxation on the frequency of transient lower oesophageal sphincter relaxations (TLOSRs). Eight normal subjects (four male, age 18-52 y) were studied after a 6-h fast using a combined manometric barostat assembly. The recording was divided into two 1-h sessions: (1) a baseline period with the barostat set at minimal distending pressure (MDP) + 2 mmHg and (2) a period with continuous glucagon or placebo infusion with barostat set at MDP + 2 mmHg. Patients were studied on two different days and randomly received glucagon (4.8 microg kg(-1) bolus followed by 9.6 microg kg(-1) h(-1) infusion) on 1 day and placebo (saline) on another. Lower oesophageal sphincter (LOS) pressure, frequency of TLOSRs, and barostat bag volumes were determined for both placebo and glucagon infusion. Glucagon induced significant fundal relaxation compared with placebo (P < 0.05) and significantly decreased baseline LEOS pressure (P < 0.05). The frequency of TLOSRs was not altered by glucagon infusion compared with placebo. Despite causing substantial proximal stomach relaxation, glucagon did not increase TLOSR frequency. This suggests that the relevant gastric mechanoreceptors responsible for triggering TLOSRs do not respond to passive elongation.     

Involvement of NO in gastric emptying of semi-solid meal in conscious pigs

The influence of non-selective nitric oxide synthase (NOS) inhibition on gastric emptying of a semi-solid meal was studied in conscious pigs. Antroduodenal motility and fundic compliance were also assessed to evaluate the mechanisms at the origin of potential alteration in gastric emptying pattern. N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg kg(-1) i.v.) delayed gastric emptying (half-emptying time of 128.98 +/- 16.86 min vs 73.74 +/- 7.73 min after saline, P < 0.05, n = 6) as a result of decreased proximal gastric emptying. No changes were observed for distal gastric emptying as a result of unchanged antral motility. Similarly, no changes were noted on duodenal motor patterns either in the fasted or in the fed state. L-NAME decreased fundic compliance in fasted state (49 +/- 11 mL mmHg(-1) vs 118 +/- 15 mL mmHg(-1) after saline, P < 0.05, n = 6). As this phenomenon is expected to increase emptying rate, the gastroparesis induced by NOS inhibition is thus likely to originate from distal resistive forces. It is concluded that NO positively modulates gastric emptying.     

Elicitation of transient lower oesophageal sphincter relaxations in response to gastric distension and meal ingestion

The aim of this study was to compare the effect of graded gastric barostat distension and meal-induced fundic relaxation on the elicitation of transient lower oesophageal sphincter relaxation (TLOSR). In 15 healthy subjects, stepwise fundic distension and oesophageal manometry were performed simultaneously. Next, the effect of meal ingestion on proximal stomach volume and lower oesophageal sphincter function was studied. During stepwise barostat distension of the proximal stomach, a significant linear correlation between intragastric pressure (r = 0.91; P < 0.01) and the TLOSR rate during inflation and subsequent deflation (r = 0.96; P < 0.01) was found. A similar relationship was found for volume. In addition, after meal ingestion, the TLOSR rate increased significantly from 1.40 +/- 3 to 5.4 +/- 1.5 h-1 (P < 0.01) and 5.2 +/- 1.7 h-1 (P < 0.01), respectively, during the first and second 30-min postprandially. However, at similar calculated intragastric volumes, barostat distension led to a significantly higher TLOSR rate than the meal. Similarly, distension-induced increase in gastric wall tension, estimated from the measured bag pressure and volume using Laplace's law, was associated with significantly higher TLOSR rates (P < 0.01). In conclusion, the rate of TLOSRs in healthy volunteers is directly related to the degree of proximal gastric distension and pressure-controlled barostat distension is a more potent trigger of TLOSRs than a meal. The latter finding suggests that tension receptor activation is an important stimulus for TLOSRs.     

Compliance, tone and sensitivity of the rectum in different subtypes of irritable bowel syndrome

Irritable bowel syndrome (IBS) consists of various subtypes. It is not known whether these subtypes share a common pathophysiology. Evaluation of motor and sensory function of the rectum using a barostat may help to explore a common pathophysiological background or differences in pathophysiology in subtypes of IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both fasting state and postprandially, using a computerized barostat in 15 patients with diarrhoea-predominant IBS (IBS-D), 14 patients with constipation-predominant IBS (IBS-C) and compared the results with those obtained in 12 healthy controls. Rectal compliance as calculated over the steep part of the pressure-volume curve (17-23 mmHg) was decreased in both IBS groups (IBS-D 8.0 +/- 1.4 mL mmHg-1; IBS-C 5.6 +/- 1.1 mL mmHg-1) compared with controls (24.7 +/- 3.5 mL mmHg-1). The perception of urge was increased only in IBS-D patients, whereas pain perception was significantly increased in both IBS groups. Spontaneous adaptive relaxation was decreased in IBS-D patients. Postprandially, rectal volume decreased significantly in the controls and in IBS-D patients, but not in IBS-C patients. In conclusion, both rectal motor and sensory characteristics are different between IBS-D and IBS-C patients. Therefore, testing of rectal visceroperception, adaptive relaxation and the rectal response to a meal may help distinguish groups of patients with different subtypes of irritable bowel syndrome.     

Effect of the selective serotonin reuptake inhibitor sertraline on gastric sensitivity and compliance in healthy humans.

Abstract Visceral hypersensitivity may contribute to symptoms in functional dyspepsia. Selective serotonin reuptake inhibitors (SSRIs) may be beneficial in functional gastrointestinal disorders. The aim of this study was to determine whether the SSRI sertraline affects gastric sensitivity and compliance in healthy humans. Ten healthy humans completed a 6-week randomized, double-blind, crossover trial of sertraline (50 mg day(-1)) vs. placebo. After each 2-week treatment, fullness, pain and nausea were rated at increasing gastric barostat distending pressures. Sensation thresholds above minimal distending pressure (MDP) were determined with a tracking method. Somatic sensory testing was performed by hand immersion in ice water. No differences were found between sertraline and placebo for symptoms as a function of distending pressure (fullness, P = 0.72; pain, P = 0.79; nausea, P = 0.41), gastric compliance (P = 0.15), median and interquartile range thresholds for first sensation [4.1 (3.5-5.7) vs. 6.2 (3.3-10.0) mmHg above MDP, P = 0.19] and pain [15.2 (8.3-21.0) vs. 15.3 (10.3-19.8) mmHg above MDP, P = 0.85], and median tolerance times for hand ice water immersion [27 (19-99) vs. 29 (20-180) s, P = 0.73]. In conclusion, sertraline had no effect on gastric sensitivity or compliance, or somatic pain tolerance in healthy humans. Studies are needed to assess the effects of SSRIs on visceral sensation and clinical symptoms in patients with functional dyspepsia.     

Role of nitric oxide in the cerebral circulation during hypotension after hemorrhage, ganglionic blockade and diazoxide in awake goats

The role of nitric oxide in cerebrovascular response to hypotension was analyzed by evaluating the changes in cerebrovascular resistance after inhibition of nitric oxide synthesis with Nw-nitro-L-arginine methyl ester (L-NAME) during three types of hypotension in conscious goats. Blood flow to one brain hemisphere was electromagnetically measured, hypotension was induced by controlled bleeding, and by i.v. administration of hexametonium (ganglionic blocker) or of diazoxide (vasodilator drug), and L-NAME was injected by i.v. route (35 mg kg-1). Under control conditions (13 goats), L-NAME increased arterial pressure from 98 +/- 3 to 123 +/- 4 mmHg and decreased cerebral blood flow from 65 +/- 3 to 40 +/- 3 ml min-1 (all P < 0.001); cerebrovascular resistance increased from 1.52 +/- 0.04 to 3.09 +/- 0.013 mmHg ml-1 min-1 (P < 0.01) (delta = 1.59 +/- 0.12 mmHg ml-1 min-1). After bleeding (five goats), mean arterial pressure decreased to 60 +/- 4 mmHg and cerebral blood flow decreased to 37 +/- 4 ml min-1 (all P < 0.01); cerebrovascular resistance did not change (1.56 +/- 0.14 vs. 1.54 +/- 0.12 mmHg ml-1 min-1, P > 0.05). During this hypotension, L-NAME increased arterial pressure to reach the normotensive values an did not affect the hypotensive values for cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 2.91 +/- 0.19 mmHg ml-1 min-1 (P < 0.01) (delta = 1.37 +/- 0.16 mmHg ml-1 min-1), and this increment is comparable to that under control conditions (P > 0.05). Ganglionic blockade (six goats) decreased arterial pressure to 67 +/- 2 mmHg) and did not affect significantly cerebral blood flow; cerebrovascular resistance decreased from 1.71 +/- 0.11 to 1.05 +/- 0.09 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 103 +/- 6 mmHg (P < 0.001), and did not affect cerebral blood flow; cerebrovascular resistance increased from the hypotensive values to 1.68 +/- 0.18 mmHg ml-1 min-1 (P < 0.01) (delta = 0.63 +/- 0.10 mmHg ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Diazoxide (six goats) decreased arterial pressure to 69 +/- 5 mmHg (P < 0.01) without changing cerebral blood flow; cerebrovascular resistance decreased from 1.89 +/- 0.11 to 1.16 +/- 0.14 mmHg ml-1 min-1 (P < 0.01). During this hypotension, L-NAME increased arterial pressure to 87 +/- 6 mmHg (P < 0.05) and did not affect the hypotensive values for cerebral blood flow (P > 0.05); cerebrovascular resistance increased from the hypotensive values to 1.53 +/- 0.13 mmHg ml-1 min-1 (P < 0.05) (delta = 0.36 +/- 0.06 mmHg-1 ml-1 min-1), and this increment was lower than under control conditions (P < 0.01). Therefore, the role of nitric oxide in cerebrovascular response to hypotension may differ in each type of hypotension, as this role during hemorrhagic hypotension may not change and during hypotension by ganglionic blockade or diazoxide may decrease. These differences may be related to changes in nitric oxide release as stimuli on the endothelium (shear stress and sympathetic activity) may vary in each type of hypotension.     

Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man

Abstract  Ghrelin increases gastric tone in the fasting state and enhances gastric emptying in gastroparesis. The aims of the study were to evaluate the effect of ghrelin on postprandial gastric tone and on meal-induced satiety in health. Ten healthy volunteers underwent a barostat study on two occasions. After determination of intra-abdominal pressure (minimal distending pressure, MDP), isobaric volume measurement was performed for 90 min at MDP + 2 mmHg. After 20 min, ghrelin (40 μg) or saline was administered i.v. over 30 min in a double-blind-randomized cross-over design, followed 10 min later by a liquid meal (200 mL, 300 kcal). Stepwise isobaric distentions (+2 mmHg per 2 min) were performed 60 min after the meal. Data (mean ± SEM) were compared using paired Student's t -test and anova . Separately, a satiety drinking test (15 mL min⁻¹ until satiety score 5) was performed on 10 subjects twice, after treatment with placebo or ghrelin. Ghrelin infusion significantly inhibited gastric accommodation (mean volume increase adjusted means 108.0 ± 50 vs 23.0 ± 49 mL, P  = 0.03, ancova with the premeal postinfusion volume as covariate) and reduced postprandial gastric volumes (197.2 ± 24.6 vs 353.5 ± 50.0 mL, P  = 0.01). Pressures inducing perception or discomfort during postprandial gastric distentions were not altered. During satiety testing, ghrelin did not alter nutrient volume ingested till maximal satiety (637.5 ± 70.9 vs 637.5 ± 56.2 mL, ns). Ghrelin administered during the meal significantly inhibits gastric accommodation in health, but this is not associated with early satiation.     

Role of NK2 receptors in gastric barosensitivity and in experimental ileus in rats

This study was performed to evaluate the role of tachykinin NK2 receptors in gastric barosensitivity and in postsurgical intestinal atony, using a selective NK2 antagonist (MEN 11420). Gastric distensions were performed in rats equipped with a gastric balloon and electrodes implanted in the neck muscles. Ileus was produced by laparotomy and caecum palpation in rats previously prepared with electrodes implanted on the proximal jejunum. Fifteen minutes before gastric distension or laparotomy, the animals received MEN 11420 (10, 100 or 200 microg kg-1 intravenously) or saline. The first distending pressure to increase the integrated neck electromyogram > 100% was considered the pain threshold. MEN 11420 (100 microg kg-1) increased significantly pain threshold (20.5 +/- 1.2 vs. 17.0 +/- 0.8 mm Hg) but did not modify gastric volumes at the three doses tested. Abdominal surgery was followed by a total inhibition of jejunal spiking activity lasting 80.4 +/- 18.7 min. MEN 11420 (10 and 100 microg kg-1) shortened the duration of motor inhibition by 36 and 39%, and induced a premature recovery of the phase III of migrating myoelectric complex at the lowest dose tested (130 +/- 32 vs. 192 +/- 28 min). We conclude that NK2 receptors, probably located on afferent fibres, are involved in gastric barosensitivity and in postsurgical intestinal atony.     

Effect of a κ-opioid agonist, i.v. JNJ-38488502, on sensation of colonic distensions in healthy male volunteers

Abstract  Kappa-opioid receptors are located on visceral pain fibres. JNJ-38488502 is a highly selective tetrapeptide κ-opioid agonist with little access to the central nervous system and low risk of central nervous system side effects. The aim of the study was to evaluate the effects of i.v. JNJ-38488502 on sensations, including pain, during colonic distension. In a single-centre study, 23 healthy adult males underwent a single-dose, randomized, double-blind crossover study of JNJ-38488502 (0.42 mg kg⁻¹ i.v. infusion) vs placebo on left colon compliance, sensory thresholds and ratings during standard distensions. One participant could not undergo sensation studies. In the other 22, JNJ-38488502 increased colonic compliance (pressure at half-maximum volume 17.9 ± 0.8 mmHg) compared to placebo (21.6 ± 0.9 mmHg, P  = 0.007). There was no significant effect on sensory thresholds which, however, were not reached by 44 mmHg in >50% of participants in both treatment phases. There were no significant treatment effects on sensory ratings to distensions at 8, 16, 24, 32 and 36 mmHg above baseline operating pressure. JNJ-38488502 was associated with increased urine output and plasma prolactin, consistent with κ-opioid receptor activation. This study concluded that i.v. JNJ-38488502 induced κ-opioid effects, but did not attenuate colonic sensations following random order colonic distension. Further studies of effects on pain sensations in health and disease are required.     

Influence of abuse history on gastric sensorimotor function in functional dyspepsia

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self-report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty-four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P  = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P  = 0.007]. The corresponding intra-balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P  = 0.013 and 579 ± 19 vs 423 ± 79 mL, P  = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P  = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.     

Influence of tegaserod on proximal gastric tone and on the perception of gastric distention in functional dyspepsia

Background Abnormalities in gastric sensorimotor function (hypersensitivity to distention and impaired meal accommodation) have been implicated in the pathophysiology of functional dyspepsia (FD). To study the effect of the 5‐HT₄ agonist tegaserod on sensitivity to gastric distention and gastric accommodation in FD. Methods Thirty FD patients (7 males, mean age 42 ± 2 years) underwent a gastric barostat study on two separate occasions, 2 weeks apart, after 5 days of pretreatment with placebo or tegaserod 6 mg b.i.d. in a double‐blind randomized order. After introduction of the barostat bag, graded isobaric distentions (2 mmHg increments/2 min) were performed to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra‐abdominal pressure [minimal distending pressure (MDP)] + 2 mmHg for 90 min, with administration of a liquid meal (200 mL; 300 kcal) after 30 min. Key Results Tegaserod had no influence on MDP (7.9 ± 0.4 vs 7.4 ± 0.4 mmHg) or fasting gastric compliance (44 ± 10 vs 61 ± 6 mL mmHg^?1) and on fasting thresholds for first perception (3.6 ± 0.4 vs 4.2 ± 0.2 mmHg above MDP) or discomfort (9.9 ± 0.7 vs 10.5 ± 0.5 mmHg above MDP). Tegaserod did not alter intra‐balloon volumes before and after the meal [respectively 146 ± 14 vs 120 ± 11 and 297 ± 28 vs 283 ± 29 mL, not significant (NS)], or the amplitude of the meal‐induced gastric relaxation (151 ± 23 vs 162 ± 23 mL, NS). In the subgroup with normal gastric emptying (n = 22), tegaserod significantly enhanced meal‐induced accommodation (126 ± 23 vs 175 ± 29 mL, anova P < 0.001). Conclusions & Inferences Tegaserod does not alter gastric sensorimotor function in FD patients as a group. In the subgroup with normal gastric emptying, tegaserod 6 mg b.i.d enhanced gastric accommodation.     

Continuous volume infusion improves circulatory stability in anesthesized rats

'Optimized' management (OM) was provided to chloralose-anesthetized rats for 12 h by combining continuous infusion (7 ml.kg-1). mechanical ventilation and strict control of acid-base equilibrium (n = 7). The chloralose-anesthetized rats managed conventionally (conventional management: CM, n = 9) received neither volume infusion, nor mechanical ventilation, nor correction of acid-base disturbances. All the OM rats completed the study while 6 out of 9 CM rats died before the end of the study period. Mean arterial pressure (MAP) remained at 100 mmHg for 12 h in the OM group. MAP stayed close to 70 mmHg in the CM group for 6 h and declined to very low levels thereafter (mean +/- S.E.M.: 46.0 +/- 3.9 mmHg at 12 h, P less than 10(-4) when compared to the other group). Central venous pressure and cardiac output remained close to baseline values for 12 h in the OM group. Acid-base equilibrium was preserved in the OM group in contrast to a severe metabolic acidosis in the CM group (pH = 7.14 +/- 0.03 at 12 h; P less than 10(-4). Such as 'optimized' management involving mechanical ventilation with oxygen, continuous infusion and acid-base monitoring may be of value to maintain circulatory stability in anesthetized rodent preparations during long periods of time, as in neurophysiological experiments.     

Neural mechanisms involved in the delay of gastric emptying of liquid elicited by acute blood volume expansion in awake rats

We have previously reported that acute blood volume expansion in awake rats delays the gastric emptying of a liquid meal, using the phenol red method. In this study we attempted to investigate the neural mechanisms involved in this phenomenon. Blood volume expansion, due to Ringer-bicarbonate infusion up to a volume equivalent to 5% of body weight, decreased the gastric emptying of a liquid meal by half (38.2 +/- 1.8 vs 18.7 +/- 3.2%, P < 0.05). The blood volume expansion effect on gastric emptying of liquid was prevented by separate pretreatments, consisting of subdiaphragmatic vagotomy or i.v. injection of hexamethonium (20 mg kg-1) or yohimbine (3 mg kg-1). Intravenous injection of atropine (0.5 mg kg-1), guanethidine (10 mg kg-1), L-NAME (3 mg kg-1), prazosin (1 mg kg-1) or propranolol (2 mg kg-1) did not prevent the blood volume expansion effect on gastric emptying. Bilateral adrenalectomy or coeliac ganglionectomy were also ineffective. The results indicate that blood volume expansion decreases gastric emptying of liquid through vagal-dependent pathways, sensitive to hexamethonium and yohimbine. Evidence for the participation of the peripheral sympathetic nervous system was not found.     

High-viscosity liquid meal accelerates gastric emptying

Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.     

Sensations of gas and pain and their relationship with compliance during distension in human colon

Background Colonic mechanosensory afferents ‘in parallel’ to circular muscle activate prevertebral ganglion reflexes; ‘in series’, afferents convey visceral sensation to the central nervous system; and pain receptors are activated with muscle distension. Our aim was to analyze the relationships of gas and pain sensations during graded distensions, and the association of sensations with colonic compliance in conscious humans. Methods The data were acquired in a prior study performed on 60 healthy volunteers (aged 18–75 years) under baseline conditions... Colonic compliance was measured in response to 4 mmHg stepwise balloon distensions to estimate pressure at half‐maximum volume (Pr_50%). Sensation ratings for gas and pain were averaged over distensions at 16, 24, 30 and 36 mmHg above baseline operating pressure. Associations between mean gas and pain ratings, and colonic compliance were assessed with Pearson correlations. Key Results Gas and pain sensations were significantly correlated at all levels of distension (all P < 0.001). Significant inverse correlations between Pr_50% and sensations of gas and pain were observed, suggesting that lower compliance was associated with lower sensations. Up to 25% of the variance in sensation may be attributed to colonic compliance. Conclusions & Inferences These data are consistent with the hypothesis that, if circumferential colonic receptors are stimulated by distension to mediate gas and pain in humans, they are, at least partly, arranged ‘in parallel’ to the muscle layer.     

Endothelin-1 stimulates sphincter of Oddi motility and decreases trans-sphincteric flow: a possible mechanism contributes to cholestasis in disease states

Endothelin-1 (ET-1) is a potent stimulator of gallbladder contractility. Its role in modulation of sphincter of Oddi (SO) motility and trans-sphincteric flow (TSF) has not been evaluated. To characterize the effects of ET-1 on SO motility and TSF, 10 anaesthetized Australian possums (in vivo, n = 6) were given graded doses of ET-1 (5-200 pmol kg-1) via closed intra-arterial injection. Blood pressure, TSF and SO motility (basal pressure, phasic amplitude, contraction frequency) were analysed. For in vitro studies, eight SO rings were subjected to 10-12-10-7 mol L-1 cumulative concentrations of ET-1 in organ bath and SO motility was measured. Data are expressed as mean +/- SEM. Statistical analysis used anova. ET-1 induced a dose-related increase in blood pressure with a maximal increase of 37.5 +/- 2.5 mmHg at 200 pmol kg-1, (P < 0.001). ET-1 also increases SO basal pressure (P < 0.001) and contraction frequency (P < 0.0001). However, the contraction amplitude was not significantly affected. ET-1 decreased TSF in a dose-related manner (P < 0.001) with cessation of TSF at the highest dose (P < 0.001). In vitro studies showed a significant increase in mean SO motility index, and frequency of contractions at higher ET-1 concentrations (10-9-10-7 mol L-1). ET-1 is a potent stimulator of SO motility resulting in a reduction in TSF.