Initiation of peristalsis by circumferential stretch of flat sheets of guinea-pig ileum.
1. Segments of isolated guinea-pig intestine, 12 mm long, were distended slowly by intraluminal fluid infusion or by mechanical stretch as either a tube or flat sheet. In all cases, at a constant threshold length, a sudden, large amplitude contraction of the circular muscle occurred orally, corresponding to the initiation of peristalsis. 2. Circumferential stretch of flat sheet preparations evoked graded contractions of the longitudinal muscle (the 'preparatory phase'), which were maintained during circular muscle contraction. This suggests that the lengthening reported during the emptying phase of peristalsis is due to mechanical interactions. 3. The threshold for peristalsis was lower with more rapid stretches and was also lower in long preparations (25 mm) compared with short preparations (5-10 mm), indicating that ascending excitatory pathways play a significant role in triggering peristalsis. 4. Stretching a preparation beyond the threshold for peristalsis evoked contractions of increasing amplitude; thus peristalsis is graded above its threshold. However, during suprathreshold stretch maintained at a constant length, contractions of the circular muscle quickly declined in amplitude and frequency. 5. Circular muscle cells had a resting membrane potential approximately 6 mV more negative than the threshold for action potentials. During slow circumferential stretch, subthreshold graded excitatory motor input to the circular muscle occurred, prior to the initiation of peristalsis. However, peristalsis was initiated by a discrete large excitatory junction potential (12 +/- 2 mV) which evoked bursts of smooth muscle action potentials and which probably arose from synchronized firing of ascending excitatory neuronal pathways. (+info)
Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism.
BACKGROUND: Atropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR). AIMS: To compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD. METHODS: Oesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 microg/kg bolus, 4 microg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period. RESULTS: Atropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0. 55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0. 15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8. 1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0. 60)) (p>0.05). CONCLUSION: In contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade. (+info)
Does the stomach remain silent after neonatal loss of its original pacemaker?: gastric motility in long-term survivors of neonatal gastric rupture.
Gastric peristaltic contractions are controlled by an intrinsic electrical pacemaker located in the mid-body along the greater curve. This study was undertaken to investigate gastric motility in long-term survivors of neonatal gastric rupture who were surgically deprived of their original pacemaker. Four patients, 1 boy and 3 girls, aged between 6 and 12 years were studied. Physiological activity of the gastric remnant was assessed in terms of electrical as well as peristaltic functions by means of electrogastrography and video-recorded barium swallow study. Electrical and mechanical pacing activities were classified into normogastria or dysrhythmia (brady- or tachygastria) according to their frequencies. In these patients, ectopic pacemakers were found to be arising just distal to the site of resection along the greater curve. Electrophysiologically, one patient was diagnosed as having normogastria, and other 3 patients were found to have dysrhythmia (2, bradygastria; 1, tachygastria) on the basis of electrogastrographic analyses. In two of three patients studied further by fluoroscopy, electrical activity agreed well with peristaltic activity. In one patient, however, electrical tachygastria was associated with peristaltic bradygastria. In conclusion, an ectopic pacemaker arises in the stomach that does not remain silent after neonatal surgical loss of its own pacemaker. Noninvasive electrogastrography seems useful in assessing electrical potentials generated by the ectopic pacemaker. (+info)
The physicochemical environment of the neonatal intestine.
Dietary intake, bacterial metabolites, and the secretion of factors (eg, proteins, electrolytes, lipid-soluble molecules, and water) by the body each contribute to the physicochemical environment of the gastrointestinal tract. Peristalsis regulates the changes along the length of the intestine. However, coordinated peristaltic responses develop as premature infants mature. In addition, the physicochemical environment of the center of the intestinal lumen differs from that of the epithelial surface. The area adjacent to the small intestinal epithelium is more acid than the bulk phase. Na+/H+ exchange antiporters in the epithelial cell apical membrane generate this acidity. Mucus maintains the acid microclimate by preventing free diffusion of hydrogen ions into the bulk phase. Development also affects these mechanisms. Changes in the lumenal environment may alter the synthesis of signaling molecules expressed by the intestinal epithelium. Thus, the epithelium, through changes in gene regulation, may act as an active interface that transmits information about the composition of the intestinal lumen to the mucosal immune system. Premature neonates are at risk of necrotizing enterocolitis, a disease almost exclusively associated with oral feeds. The pathogenesis of this condition may, in part, be due to the immaturity of the interactions between the physicochemical environment of the lumen and intestine. (+info)
Quantitative analysis of peristalsis in the guinea-pig small intestine using spatio-temporal maps.
1. Peristalsis was evoked in guinea-pig small intestine by slow fluid infusion and recorded onto video and digitized. Spatio-temporal maps of diameter and longitudinal movement were constructed and parameters of motion were calculated. 2. During the filling of the isolated segments of intestine, rhythmic local longitudinal movements were observed at several points along the preparation. These phasic longitudinal muscle contractions were associated with small but significant local increases in diameter and probably reflect a passive mechanical coupling by connective tissue in the gut wall. In addition, occasional synchronized longitudinal muscle contractions caused net shortening of the preparation and always preceded the onset of peristaltic emptying. 3. Peristaltic emptying was characterized by a contraction of the circular muscle which usually started at the oral end of the preparation, that propagated aborally, propelling the contents. However, in 19 % of trials, the first circular muscle contraction occurred in the aboral half of the preparation. 4. The propagation of peristalsis consisted of separate sequential circular muscle contractions several centimetres long, particularly in the oral half of the preparation, giving a 'step-like' appearance to the spatio-temporal map. The gut was transiently distended aboral to the propagating circular muscle contraction due to the propulsion of contents. 5. At each point in the preparation, the longitudinal muscle remained contracted during the propulsive part of the circular muscle contraction. Only when the circular muscle contraction became lumen occlusive did lengthening of the longitudinal muscle take place. 6. Spatio-temporal maps are a powerful tool to visualize and analyse the complexity of gastrointestinal motility patterns. (+info)
Does the guinea-pig ileum obey the 'law of the intestine'?
1. We report the first simultaneous mechanical reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers of the guinea-pig ileum following mucosal stimulation and distension in vitro. 2. Dissection techniques were used to prevent mechanical interaction between the LM and CM layers both oral and anal to a stimulus site. 3. All graded stimuli produced graded contractions of both the LM and CM orally and anally to the stimulus. Contractions occurred synchronously in the LM and CM and under no circumstances were inhibitory responses recorded in either muscle layer, despite the presence of ongoing cholinergic tone in both the LM and CM. Contractions were abolished by tetrodotoxin (1.6 microM). 4. Local brush stroking of the mucosa evoked a peristaltic wave which readily conducted distally over 13 cm, without the presence of fluid in the lumen. No descending relaxation was observed. 5. Apamin (300 nM) disrupted evoked peristaltic waves and significantly increased the rate-of-rise of the LM and CM contractions anal to a stimulus, and the LM oral to a stimulus. 6. Nomega-nitro-L-arginine (100 microM), a nitric oxide synthesis inhibitor, had no overall significant effect on the characteristics of the LM and CM contractions, although on occasion an enhancement in their peak amplitude was noted. 7. It is suggested that the guinea-pig ileum does not conform to the 'law of the intestine' as postulated by Bayliss & Starling (1899). Rather, local physiological stimulation of the ileum elicits a contraction both orally and anally to a stimulus, which occurs synchronously in both the CM and LM layers. Apamin-sensitive inhibitory neurotransmission modulates the rate-of-rise of the anal contraction of the CM, possibly to generate distal propulsion. (+info)
Stimulant action of pituitary adenylate cyclase-activating peptide on normal and drug-compromised peristalsis in the guinea-pig intestine.
1. Pituitary adenylate cyclase-activating peptide (PACAP) is known to influence the activity of intestinal smooth muscle. This study set out to examine the action of PACAP on normal and drug-inhibited peristalsis and to shed light on its site and mode of action. 2. Peristalsis in isolated segments of the guinea-pig small intestine was elicited by distension through a rise of the intraluminal pressure. Drug-induced motility changes were quantified by alterations of the peristaltic pressure threshold at which aborally moving peristaltic contractions were triggered. 3. PACAP (1-30 nM) stimulated normal peristalsis as deduced from a concentration-related decrease in the peristaltic pressure threshold (maximum decrease by 55%). The peptide's stimulant effect remained intact in segments pre-exposed to apamin (0.5 microM), N-nitro-L-arginine methyl ester (300 microM), naloxone (0.5 microM), atropine (1 microM) plus naloxone (0.5 microM) or hexamethonium (100 microM) plus naloxone (0.5 microM). 4. PACAP (10 nM) restored peristalsis blocked by morphine (10 microM), noradrenaline (1 microM) or N6-cyclopentyladenosine (0.3 microM) and partially reinstated peristalsis blocked by Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine (100 microM) but failed to revive peristalsis blocked by hexamethonium (100 microM) or atropine (1 microM). The peptide's spectrum of properistaltic activity differed from that of naloxone (0.5 microM) and forskolin (0.3 microM). 5. The distension-induced ascending reflex contraction of the circular muscle was facilitated by PACAP (1-30 nM) which itself evoked transient nerve-mediated contractions of intestinal segment preparations. 6. These data show that PACAP stimulates normal peristalsis and counteracts drug-induced peristaltic arrest by a stimulant action on excitatory enteric motor pathways, presumably at the intrinsic sensory neurone level. The action of PACAP seems to involve multiple signalling mechanisms including stimulation of adenylate cyclase. (+info)
Myogenic mechanism for peristalsis in the cat esophagus.
A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 microM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K(+) concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves. (+info)