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Biomedical subjects

D L Wingate

Publications and source records attributed to D L Wingate.

At least 73 records · Page 4Linked to original sources

Effect of stress on oesophageal motor function in normal subjects and in patients with the irritable bowel syndrome.

Stress can modulate the motor function of the stomach, small bowel, and colon in healthy subjects, and of the small bowel and colon in patients with the irritable bowel syndrome (IBS). The effect of stress on oesophageal motility in eight healthy subjects and in eight IBS patients was studied, using two pressure transducers positioned just above the lower oesophageal sphincter and 5 cm proximally. Stressors were: a video arcade game, delayed audio feedback, and hand immersion in cold water. Each stress period was followed by five swallows of water. Frequency and amplitude of oesophageal contractions and the number of simultaneous and multipeaked contractions were manually counted for each stress period and compared to the preceding rest period. Frequency of contractions (per minute) tended to decrease during stress periods, but achieved significance only with the video arcade game in the control group (2.0 (0.6) v 1.2 (0.4); p less than 0.01). No other trend was evident in either control or IBS patients. No abnormalities of oesophageal body function were recorded in IBS patients either in basal conditions, or under stress. Unlike the more complex motor programmes elsewhere in the gut, the preprogrammed nature of oesophageal peristalsis is not modulated by stress.

Adult↗

Effects of osmoreceptor stimulation on human duodenal motor activity.

The motor responses of the human duodenum to saline solutions of varying osmolality were examined in order to investigate the possible role played by the upper intestine in the control of gastric efflux of hyperosmolar material. During fasting, delivery of the solutions into the duodenum increased duodenal motor activity and intraduodenal pressure, the magnitude of the response increasing with osmolality. At the highest osmolalities, a regular duodenal motor pattern was induced in some individuals which was indistinguishable from fasting phase III activity. After feeding, hyperosmolar saline again increased motor activity. In addition, the transit of an intraduodenal marker to the caecum was accelerated. These findings support the concept that the duodenum is both sensitive and responsive to its intraluminal content. The motor responses additionally appear to function to clear excessively stimulating intraluminal material from the duodenal lumen and may also contribute to the 'postpyloric' resistance which is known to exert control of normal gastric emptying.

Adult↗

Physiological enteric stimulation elicits cardiovascular reflexes in the rat.

By use of anesthetized rats, parameters for the activation of cardiovascular reflexes by stimulation of gastric or hepatic receptors have been established. For reflex activation, the mean minimum intragastric volume was 4 ml, and the mean minimum rate of hepatic portal vein infusion was 0.3 ml/min. Subdiaphragmatic vagotomy affected the response to gastric distension but did not appear to affect the response to hepatic portal vein infusion, indicating that vagal afferents are involved in mediating gastric-cardiovascular but not hepatic-cardiovascular reflexes. Experiments designed to emphasize the vagal component of the response to gastric distension confirmed this finding. Antagonist effects indicated that the tachycardia was mediated by beta-adrenoreceptor stimulation and that the pressor response was mainly mediated by alpha-adrenoreceptors. The data show that stimuli used in experiments to assess central processing of sensory information from the gastrointestinal tract can activate cardiovascular reflexes. Caution in the design of such experiments and in the interpretation of the data generated is indicated.

Animals↗

Effect of pirenzepine on oesophageal, gastric, and enteric motor function in man.

The effect of pirenzepine on oesophageal, gastric, and enteric motor function was evaluated in six healthy volunteers. Each subject was studied before and after taking pirenzepine, 100 mg/day, for 3 days. Half and complete gastric emptying times of clear liquid, assessed by epigastric impedance, were significantly delayed by the drug: 6.16 +/- 1.74 min and 13.8 +/- 4.64 min versus 16.65 +/- 3.03 min and 25.1 +/- 8.2 min, respectively (p less than 0.05). Enteric motility was assessed by manometry, and variables studied were the duration of the various phases of the migratory motility complex, the frequency of contractions in phase III, and the amplitude of contractions in phases II, III, and in the postprandial period. Only phase I was affected and was significantly prolonged by the drug: 16.08 +/- 5.94 min versus 31.65 +/- 12.88 min (p less than 0.01). Oesophageal motility was assessed by manometry. Variables studied were amplitude and duration of contractions in the body of the oesophagus, and lower oesophageal sphincter pressure. Results were not significantly changed by the drug. We conclude that pirenzepine, given at a dose used for treatment of peptic ulcer disease, significantly delays the gastric emptying of liquids, has minimal effect on enteric motility, and has no effect on oesophageal motility. The effect on gastric emptying may be therapeutically useful by reducing the acid load on the duodenum in duodenal ulcer disease.

Adult↗

Intracellular recordings from myenteric neurones in the human colon.

1. Intracellular recordings were made from cells in the myenteric plexus of the human colon in freshly dissected tissue obtained from patients undergoing surgery for the removal of carcinomas or diverticular bowel. 2. Twenty-seven cells from ten preparations were classified as neurones and had overshooting action potentials, an average resting potential of -54 +/- 9 mV, an average input impedance of 1.05 +/- 0.59 x 10(8) omega and a variety of synaptic inputs. 3. Twenty-three (out of twenty-five neurones tested) received nicotinic fast excitatory synaptic inputs (fast e.p.s.p.s) that were blocked reversibly by hexamethonium and mimicked by acetylcholine. These nerve cells bore a close resemblance to S cells that have been characterized in the guinea-pig small-bowel myenteric plexus. 4. One cell had a long after-hyperpolarization following its impulses and was similar to AH cells in the guinea-pig small bowel. 5. Three neurones received inhibitory synaptic inputs, up to 15 mV in amplitude, lasting up to 10 s, associated with a decrease in input impedance and with a reversal potential between -80 and -90 mV. 6. Slow excitatory synaptic potentials were only detected in the single AH cell. The slow e.p.s.p. was associated with a depolarization of up to 12 mV, an increase in excitability and an increase in the input impedance of the neurone. 7. The proportion of S and AH cells differ considerably from that reported in the guinea-pig small-bowel preparation. Possible causes of the differences are discussed.

Acetylcholine↗

Modulation of human upper gastrointestinal motility by rectal distension.

The effects of rectal distension on upper gastrointestinal motility were investigated in six healthy subjects. On a control day, gastric and duodenal motor activity was recorded for nine hours of fasting and for four hours after a meal, duodeno-caecal transit being assessed in both interdigestive and digestive states. Motor activity and transit were also measured on a test day during which the rectum was distended for one hour during fasting and for one hour postprandially. Control and test days were randomised. During fasting, rectal distension increased the incidence of migrating motor complexes (0.8 +/- 0.3 v 0.5 +/- 0.2 h; p less than 0.01) and reduced the duodenal phase 2 motility index to 66 +/- 45% of that observed on the control day (p less than 0.01). Further, duodeno-caecal transit time was increased by rectal distension (99 +/- 30 v 71 +/- 35 min; p less than 0.05). Postprandially, the period of rectal distension was marked by a reduction in the duodenal motility index to 24 +/- 13% of that observed during the comparable period on the control day (p less than 0.001) and a concomitant increase in duodeno-caecal transit time (113 +/- 22 v 80 +/- 17 min; p less than 0.01). We conclude that upper gastrointestinal motor activity, the effector of luminal transit, may be profoundly influenced by stimulation of distal afferents.

Action Potentials↗

Gastro-oesophageal reflux and the migrating motor complex.

Distal oesophageal pH and gastroduodenal motor activity were recorded simultaneously throughout nocturnal (23 30-08 30 h) and diurnal (08 30-17 30 h) periods of fasting in seven healthy subjects. At night, episodes of gastro-oesophageal reflux (GOR) accounted for 1.2 +/- 0.7% of recording time. Periods of gastric motor activity, representing the gastric component of the migrating motor complex (MMC), recurred every 78 +/- 31 min during the night and were interspersed with periods of gastric motor quiescence. Nocturnal episodes of GOR during periods of gastric motor activity were of longer duration (p less than 0.001) and more frequent (p less than 0.005) than during periods of gastric motor quiescence. At night, periodic gastric motor activity was thus correlated (p less than 0.001) with an increase in the duration and number of GOR episodes and associated with a 100-fold increase in oesophageal acid exposure. During the day, the gastric component of the MMC, recurring every 131 +/- 64 min, was correlated (p less than 0.02) with an increase in the duration and number of GOR episodes, and a three fold increase in oesophageal acid exposure. Further, 89% of nocturnal, and 83% of diurnal gastric MMCs were temporally associated with episodes of GOR. We conclude that fasting episodes of GOR occur coincidentally with the gastric component of the MMC.

Adult↗

Effects of different types of stress and of "prokinetic" drugs on the control of the fasting motor complex in humans.

Upper small bowel motility was continuously recorded for 36-48 h in 37 healthy ambulant volunteers using twin pressure-sensitive radiotelemetric capsules tethered in the small bowel. Each study began with a 24-h period that was free of applied stress. The second 24-h period included 7 h of intermittent psychological stress during the day and brief episodes of acute stress during the following night, except in the members of a control group to whom no stress was applied. Stress responses were assessed from cardiovascular status and self-reported visual analogue scales. Applied stress during the second day significantly inhibited the incidence of fasting migrating motor complexes compared with the first day; when no stress was applied there was no reduction in migrating motor complexes. Nocturnal stress was less effective in the inhibition of migrating motor complexes. All the stressors induced positive cardiovascular and subjective stress responses. The stress-induced inhibition of migrating motor complexes was reversed by oral metoclopramide; however, the drug did not reverse the cardiovascular or subjective response to stress. In contrast, domperidone did not inhibit the gastrointestinal effects of stress. Neither drug appeared to influence small bowel motility under normal conditions.

Adult↗

Convergence of sensory information from abdominal viscera in the rat brain stem.

This study was carried out to establish whether there was convergence of sensory information in the rat brain stem stimulated by physiological activation of gastric mechanoreceptors and hepatic glucoreceptors. Extracellular recordings were made from single neurons in the region of the dorsal vagal nucleus and nucleus of the solitary tract in the medulla. The responses of these neurons to gastric distension, hepatic portal vein perfusion of isotonic D-glucose, and hepatic portal vein infusion of isotonic saline were studied. Fifty-six neurons were studied; it was found that there was no significant difference in the proportion of neurons responding to gastric distension compared with the number responding to either form of hepatic stimulation. In 20 neurons (all 3 types of stimulation were tested on the same neuron), both excitation and inhibition were observed with both forms of visceral stimulation. Of the seven of these neurons that responded to hepatic portal vein infusion, four of them also had an input from gastric mechanoreceptors. Only three of the neurons that responded to hepatic stimulation showed a specific response to hepatic glucose perfusion; in the remainder a component of the response was due to the infusion of the volume itself. The results from these experiments have demonstrated an apparently weak functional synaptic projection carried by hepatic vagal afferents, particularly those responding to changes in portal glucose concentration, which may indicate a rather diffuse and nonspecific sensory system in the liver. These results have also demonstrated the convergence onto neurons in the brain stem of information from gastric and hepatic enteroceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The irritable bowel syndrome: a paroxysmal motor disorder.

Upper small bowel motility was recorded for more than 30 h in each of 22 patients with the irritable bowel syndrome (IBS) and in two control groups, one consisting of 10 healthy volunteers and the other of 5 patients with inflammatory bowel disease. When subjects underwent a long period of intermittent mental stress, one or more of three motor abnormalities occurred in 19 patients; and only one abnormality was seen in 1 control (p less than 0.0001). These abnormalities were the total abolition of migrating motor complexes under stress, and abnormal irregular contractile activity, which was either spontaneous or evoked by stress. Sometimes the irregular contractile activity coincided with the occurrence of typical IBS symptoms. Males predominated (p = 0.05) among those with spontaneous irregular motor activity, who tended to have more symptoms (p = 0.014) than did those affected only by stress. The data suggest that irritable bowel syndrome is a paroxysmal motor disorder which may be detected in the small bowel and which may be either spontaneous or evoked.

Adult↗

The effect of diet on small intestinal and biliary tract function.

During fasting, the motor and secretory activity of the small intestine and biliary tract is characterized by periodic oscillation between activity and quiescence. On fasting, motor and secretory activity is continuous although variable. Different phases of activity are marked by variations in plasma levels of gastrointestinal regulatory peptides, but current evidence indicates that the interdigestive periodicity is generated in the intrinsic innervation, while the response to food is mediated by vagal sensory receptors. It is now clear that the extent and complexity of neurochemical regulation of gut function by both the enteric and central nervous systems has been hitherto underestimated.

Animals↗

Organization of fasting and postprandial myoelectric activity in stomach and duodenum of conscious dogs.

In conscious dogs, contractile and myoelectric activity was recorded from force transducers and monopolar electrodes chronically implanted in the serosal surface of the proximal and distal stomach. Periodic activity during fasting was characterized at each site. Proximally, activity fronts consisted of a series of regular large-amplitude contractions, without correlated myoelectric changes, occurring at 50-s intervals. The distal activity front comprised a series of bursts of two to three contractions 11 s apart, with each burst in phase with a proximal contraction. Only during the burst sequence was each electrical slow wave associated with a spike burst (1:1 phase locking). In contrast, 1:1 phase locking characterized the electrical correlates of the duodenal activity front. Oral feeding abolished periodic activity for at least 3 h. Postprandially, the proximal stomach remained electrically silent; in the duodenum spike bursts were intermittently associated with regular slow waves, but in the distal stomach regular low-amplitude contractions were characterized electrically by 1:1 phase-locked spike bursts and slow waves. These observations suggest that the proximal stomach regulates the canine fasting activity front and require modification of the concept that 1:1 phase locking is a necessary condition of the activity front.

Action Potentials↗

Central representation of arrival of nutrient in the duodenum.

This study was carried out to assess the extent to which the appearance of a nutrient (D-glucose) in the duodenum of the anesthetized rat is signaled within the medulla. Recordings were made from single neurons in the region of the dorsal vagal nucleus and the nucleus tractus solitarius during constant single-pass perfusion of the duodenum with isotonic saline or D-glucose at 37 degrees C. In some experiments, the response of medullary neurons to acute gastric distension was also recorded. Of the 41 spontaneously firing neurons that were studied, 20 showed changes in firing rate when glucose replaced saline in the duodenal perfusate, 9 showed decreasing firing rates, and 11 showed increased firing rates. The spontaneous firing rate of glucose-sensitive neurons was significantly slower than that of glucose-insensitive neurons. In 14 neurons tested with both glucose perfusion and gastric distension, 6 responded to only one of the two stimuli, while only 2 responded to both. It is clear that the arrival of nutrient within the duodenum is rapidly signaled within the central nervous system, suggesting the possibility of neural as well as humoral modulation of the physiological changes seen on feeding.

Animal Nutritional Physiological Phenomena↗