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Reparative myogenesis in long-term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population.

This study, conducted on 25-month denervated rat hindlimb muscles, was directed toward elucidating the basis for the poor regeneration that is observed in long-term denervated muscles. Despite a approximately 97.6% loss in mean cross-sectional area of muscle fibers, the muscles retained their fascicular arrangement, with the fascicles containing approximately 1.5 times more fibers than age-matched control muscles. At least three distinct types of muscle fibers were observed: degenerating, persisting (original), and newly formed (regenerated) fibers. A majority of newly formed fibers did not appear to undergo complete maturation, and morphologically they resembled myotubes. Sites of former motor end-plates remained identifiable in persisting muscle fibers. Nuclear death was seen in all types of muscle fibers, especially in degenerating fibers. Nevertheless, the severely atrophic skeletal muscles continued to express developmentally and functionally important proteins, such as MyoD, myogenin, adult and embryonic subunits of the nicotinic acetylcholine receptor, and neural-cell adhesion molecule. Despite the prolonged period of denervation, slow and fast types of myosin were found in surviving muscle fibers. The number of satellite cells was significantly reduced in long-term denervated muscles, as compared with age-matched control muscles. In 25-month denervated muscle, satellite cells were only attached to persisting muscle fibers, but were never seen on newly formed fibers. Our data suggest that the absence of satellite cells in a population of immature newly formed muscle fibers that has arisen as a result of continuous reparative myogenesis may be a crucial, although not necessarily the only, factor underlying the poor regenerative ability of long-term denervated muscle.

Age Factors↗

Efferent limb myoneural and luminal continuity and postgastrectomy gastric emptying.

Delayed gastric emptying and altered upper gut transit or both are common following Roux-en-Y gastrojejunostomy and are thought to be due to altered efferent limb transit secondary to isolation of the Roux limb from the duodenal pacemaker. We postulated that preservation of myoneural continuity of the Roux limb with the duodenal pacemaker would enhance solid gastric emptying, while division of the afferent limb of a Billroth II gastrojejunostomy (B-II), isolating the efferent jejunal limb from the duodenal pacemaker, would slow gastric emptying. Solid gastric emptying was measured in 14 dogs, who then underwent gastric vagotomy and antrectomy. Eight animals were reconstructed with a Roux-en-Y gastrojejunostomy, preserving myoneural but not luminal continuity of the Roux limb with the afferent limb via a muscularis bridge, while six dogs underwent standard B-II gastrojejunostomy. Serosal electrodes were placed on the afferent and efferent jejunal limbs. Gastric emptying was restudied, with fed and fasted myoelectric recordings. The bridge was then divided to create a standard Roux, while the afferent limb was transected and reanastomosed just proximal to the gastrojejunostomy in the B-II dogs to isolate the efferent limb from the duodenal pacemaker, with repeat studies. Bridge dogs had delayed solid gastric emptying compared to their preoperative state, despite normal efferent limb motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Roux-en-Y↗

Numerical simulation of motility patterns of the small bowel. 1. formulation of a mathematical model.

A complete mathematical model of the periodic myoelectrical activity of a functional unit of the small intestine is presented. Based on real morphological and electrophysiological data, the model assumes that: the functional unit is an electromyogenic syncytium; the kinetics of L-type Ca2+, T-type Ca2+, Ca2+-activated K+, voltage dependent K+and Cl-channels determine the electrical activity of the functional unit; the enteric nervous system is satisfactorily represented by an efferent cholinergic neuron that provides an excitatory input to the functional unit through receptor-linked L-type Ca2+channels and by an afferent pathway composed of the primary and secondary sensory neurons; the dynamics of propagation of the wave of depolarization along the unmyelinated nerve axons satisfy the Hodgkin-Huxley model; the electrical activity of the neural soma reflects the interaction of N-type Ca2+channels, Ca2+-activated K+and voltage dependent Na+, K+and Cl-channels; the smooth muscle syncytium of the locus is a null-dimensional contractile system. With the proposed model the dynamics of active force generation are determined entirely by the concentration of cytosolic calcium. The model describes: the mechanical excitation of the free nerve endings of the mechanoreceptor of the receptive field of the pathway; the electrical processes of the propagation of excitation along the afferent and efferent neural circuits; the chemical mechanisms of nerve-pulse transmission at the synaptic zones; the slow wave and bursting type electrical activity; cytosolic calcium concentration; the dynamics of active force generation. Numerical simulations have shown that the model can display different electrical patterns and mechanical responses of the locus. The results show good qualitative and quantitative agreement with the results of experiments conducted on the small intestine.

Enteric Nervous System↗

Numerical simulation of motility patterns of the small bowel. II. Comparative pharmacological validation of a mathematical model.

A model of a locus of the small bowel, described earlier by the authors (Miftakhov et al., 1999) was validated in a comparison of the results of numerical simulations of pharmacological compounds to their effects in biological studies. The actions of the following four classes of drugs were simulated, those: (i) acting on the sarcoplasmic reticulum, (ii) altering the permeability of L- and T-type Ca(2+)channels on the smooth muscle membrane, (iii) motilides, and (iv) benzodiazepines. The strong qualitative resemblance between the theoretical and experimental results supports the robustness of the model.

Benzodiazepines↗

Gastrointestinal recovery following laparoscopic vs open colon surgery.

BACKGROUND: We prospectively studied the recovery of gastrointestinal motility in patients undergoing laparoscopic (LAP, n = 7) or open (OPEN, n = 7) colon resections. METHODS: At operation, bipolar recording electrodes were placed on the proximal and distal antrum, the proximal site of the colonic anastomosis, and the rectosigmoid for postoperative myoelectric recordings. RESULTS: Shorter postoperative hospitalization and earlier resumption of a regular diet of the LAP group just barely failed to achieve significant differences when compared with the OPEN group (p = 0.091, p = 0.050, respectively). There were no differences between groups for slow wave frequency, amplitude, or dysrhythmias in the antrum, nor for return of discrete (DERA) and continuous (CERA) electrical response activity in the colon. Percentage of slow waves with spike activity tended to increase with passage of time postoperatively in both groups. There was a significant difference between POD 3 and 7+ in the LAP group (p < 0.05). However, there were no significant differences in the percentage of slow waves with spike activities between groups on any postoperative day. CONCLUSIONS: The potential benefits of using a laparoscopic approach to colon resection are not clearly confirmed by these data. While such an approach may possibly result in shorter hospitalization, it appears to offer at best only modest increases in the rapidity of recovery of gastrointestinal function.

Anastomosis, Surgical↗

[Model of electromyographic study of small intestinal transplants in the rat].

Adequate motility of a small bowel transplant is a prerequisite for its resorptive function as well as its self-purging capacity. The literature contains some reports on changes in motility following denervation or transplantation, but none on the impact of acute rejection on motility of small bowel grafts. Therefore an experimental model was established to meet the following criteria: orthotopic position of graft, adequate nutritional status even when graft is functionally impaired, chronically implantable electrodes attached to graft and corresponding segment of native bowel, isogeneic or allogeneic set-up. 10 cm of proximal jejunum were transplanted from Lewis donors to five Lewis recipients in an orthotopic position just distal of the ligament of Treitz without resection of native small bowel. Three bipolar electrodes were sutured to the graft and the same number to the subsequent recipient bowel. Serial myoelectric measurements were taken until the end of week 3. From day 5 on, migratory myoelectric complexes independent of myoelectric activities of native bowel were recorded. Pacemaker frequency of the graft was found to be the same as that of the transsected native small bowel. This early reappearance of myoelectric activities makes this model suitable for comparative studies of small bowel transplant motility and in particular its changes during rejection, since even in strongly allogeneic combinations Lewis small bowel does not show histological signs of rejection before day 6.

Animals↗

Correlation between pressure changes and solid transport in the human left colon.

A study was made to correlate colonic pressure changes and solid transport in six volunteers with a left terminal colostomy. A minimally deformable solid (sham fecaloma) 2 cm in diameter was placed in the colonic lumen together with three perfusion catheters connected to the exterior via a semi-rigid rod to record movement and pressure changes. The results obtained indicate the presence of two types of segmentary motor phenomena: those that cause displacement and those that do not. Both reflect synchronous pressure increments, although the Displacing Motor Phenomena exhibit an aborally-directed pressure gradient in contrast to the orally orientated gradient in Non-displacing Motor Phenomena (P = 0.003). The Displacing Motor Phenomena cause rapid exit of the solid from the colostomy, but with a short mean trajectory (4.2 cm). Thus, segmentary contractions may generate forward propulsion provided that aborally-directed pressure gradients occur. A slow aboral displacement also occurs during periods of motor quiescence. This may be explained by tonic contractions undetected by conventional manometry.

Catheterization↗

Suppression of myoelectrical activity of gastric smooth muscle by endogenous gastric prostaglandin E2.

The myoelectrical activity of the gastric smooth muscle, recorded by a bipolar electrode placed at the gastric antrum in rats, could be recorded when the stomach was distended with 5 ml of physiological saline. This activity may be induced by a mucosal reflex and was inhibited both by atropine and by pirenzepine. Replacement of physiological saline with solutions of NaCl suppressed this myoelectrical activity. This suppression was dependent on the concentrations of NaCl in the solutions, from 0.3 to 1.0 M. Pretreatment with indomethacin (10 mg/kg, intravenous) completely prevented this suppression induced by different concentrations of NaCl solutions. Intragastric administration of 1.0 M NaCl in solution caused an increase in the levels of PGE2 in the gastric lumen. Intragastric administration of OU-1308, a synthetic derivative of PGE1, also suppressed the myoelectrical activity in a dose-dependent manner. It is concluded that the suppression of gastric myoelectrical activity by hyperosmolar NaCl may be attributable to the generation of endogenous PGE2 in the stomach.

Alprostadil↗

Reversal of gastric electrical dysrhythmias by cisapride in children with functional dyspepsia. Report of three cases.

Three children (ages 5, 7.6, and 8 years), with recurrent unexplained upper abdominal symptoms such as vomiting, epigastric pain, anorexia, early satiety and without structural or mucosal abnormalities of gastrointestinal tract, underwent electrogastrography (EGG)--recording of gastric electrical activity using cutaneous electrodes positioned on the epigastric region and connected to a recording polygraph. Frequency of EGG signals was analyzed by fast Fourier transform. Significant changes of fasting and fed gastric myoelectrical activity (tachygastria, bradygastria, flatline pattern) were recorded in the three patients; furthermore, gastric emptying (GE) of a solid-liquid mixed meal, measured by ultrasonography, was significantly prolonged in them. A follow-up study was carried out after an eight-week course with oral cisapride: in all patients symptoms improved, GE time normalized, and EGG analysis showed normal electrical rhythm. It is suggested that gastric dysrhythmias can play a pathogenetic role in patients with functional gastrointestinal symptoms and that symptomatic improvement is accompanied by normalization of gastric electrical rhythm.

Child↗

Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans.

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenal lipid and antral tachygastria in conscious dog.

The myoelectrical and motor response of the antropyloroduodenal region to intraduodenal nutrient stimulation or antral tachygastria represent useful models for, respectively, physiological and pathophysiological gastric stasis to test the efficacy of prokinetic drugs. We evaluated the effects of an intravenous bolus of cisapride (0.63 mg/kg) on the myoelectrical and motor response of the antropyloroduodenal region to an intraduodenal triglyceride emulsion (10% Intralipid, 0.5 ml/min) or antral tachygastria in conscious dogs. Intraduodenal lipid suppressed antral motility (P < 0.05, compared to intraduodenal saline) and stimulated phasic pyloric contractions (P < 0.01, compared to intraduodenal saline), a motor pattern known to be associated with delayed gastric emptying. During intraduodenal lipid stimulation cisapride virtually abolished all isolated pyloric motor events (P < 0.05) and stimulated antral and duodenal motility (P < 0.05 for both) and antropyloroduodenal coordination (65% versus 15%; P < 0.05). Antral tachygastria was associated with a higher number of isolated pyloric motor events in the fasted state [0.8 (0.7-1.1) per minute versus 0.2 (0-0.3) per minute; P < 0.05], but not during intraduodenal lipid stimulation [1.1 (0.9-1.7) per minute versus 1.2 (1.0-1.9) per minute; NS]. Cisapride decreased the number and duration of spontaneous episodes of antral tachygastria during intraduodenal saline and lipid infusion (P < 0.05 for both) and abolished the tachygastria-associated motor patterns. Cisapride induced a 20% decrease in the antral slow-wave frequency during intraduodenal saline and lipid, irrespective of gastric pacemaker rhythm. We conclude that: (1) cisapride overcomes feedback from small intestinal lipid receptors on myoelectrical and motor activities of the antropyloroduodenal region and decreases antral slow-wave frequency, and (2) cisapride inhibits antral tachygastria and tachygastria-associated motor patterns. These effects may contribute to the effective gastrokinetic properties of cisapride in physiological and certain forms of pathophysiological gastric stasis.

Animals↗

Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy.

In patients with diabetes mellitus and gastroparesis, dysrhythmias of gastric myoelectrical activity, especially tachygastrias, are thought to be involved in the pathogenesis of dyspeptic symptoms. Using surface electrogastrography we studied the prevalence of these abnormalities, and their relationships to dyspeptic symptoms and the extent of cardiac autonomic neuropathy in 30 euglycemic patients with type I diabetes mellitus and 12 controls. Neither in the fasting nor in the postprandial state were differences in mean frequency of gastric electrical control activity and its variability found between patients and controls. In the fasting state, the power content of the 3 cpm component in the power spectrum of the electrogastrogram was even higher in patients than in controls (P = 0.049). In the fasting state, second harmonics of the 3 cpm fundamental gastric signal were seen more often in patients than in controls (P = 0.03). In patients with symptoms during the study, no second harmonics were found after the meal. The postprandial/fasting power ratio was decreased in patients with symptoms during the study as compared to patients without symptoms and controls (P < 0.05). The incidence of dysrhythmias, such as tachygastrias and bradygastrias, was not higher in patients than in controls (17% and 8%, respectively). No correlation was found between electrogastrographic parameters and the severity of autonomic neuropathy or dyspeptic symptoms scored before the study. In conclusion, this study has shown that patients with type I diabetes mellitus and autonomic neuropathy studied under euglycemic conditions do not have grossly disturbed myoelectrical activity, except when symptomatic during the study.

Autonomic Nervous System Diseases↗

Effect of ileal oleate on interdigestive intestinal motility of the dog.

To determine the effect of ileal oleate on fasting intestinal motility, pairs of duodenal and ileal catheters and bipolar duodenal and jejunal seromuscular electrodes were surgically implanted in six dogs. The ileum was perfused with either normal saline (154 mM NaCl) or oleic acid emulsion (152 mM), while intestinal myoelectric activity was continuously monitored. For transit studies, a bolus of [3H]PEG was injected into the duodenum, and jejunal and ileal alliquots were collected every 15 min for a 6-hr study period. Plasma samples were collected for radioimmunoassays of peptide YY and enteroglucagon. Ileal oleate infusion increased the MMC cycle length and decreased the number of MMCs (P < 0.001) and the myoelectric spike-burst frequency/10 min in the duodenum (P < 0.05). Both duodenal-jejunal (P < 0.05) and duodenal-ileal transit (P < 0.01) were delayed markedly by ileal perfusion with oleic acid emulsion as compared to control studies. Ileal oleate increased plasma levels of peptide YY (P < 0.01) and enteroglucagon (P < 0.01). Ileal perfusion with oleate therefore activated the so-called "ileal brake," diminishing duodenal myoelectric spike bursts and slowing intestinal transit while concurrently increasing plasma levels of peptide YY and enteroglucagon.

Animals↗

Bipolar electrode implantation for myoelectrical recordings of rat bowel.

This report describes a technique to implant bipolar electrodes into the rat bowel. We implanted a total of 129 pairs of bipolar electrodes into the bowel of rats. 124 pairs of electrodes (96.3%) have continuously functioned allowing repeated myoelectrical readings. Of these, 69 electrodes functioned over 8 weeks. Only 5 electrodes (3.7%) failed. The advantage of our technique includes: (1) high success rate in implantation, (2) long term durability, and (3) less technical difficulty.

Animals↗

Electrogastroenterographic examination of 22 patients before and after cholecystectomy.

The object of this study was to define the pattern of gastrointestinal myoelectrical activity before and after cholecystectomy. After surgery, on the first postoperative day, the mean and maximal activities of the gastrointestinal tracts decreased significantly, but there was no significant change in the pattern and the duration of the nonreactive period. A dyskinetic effect and/or weakness of electrical activity was observed in all patients before operation, and the same pattern persisted after operation for one month. This suggests the future onset of the so-called postcholecystectomy syndrome, which may result from the fundamental pathological effect of gallstones.

Adult↗

Role of sham feeding in postprandial changes of gastric myoelectrical activity.

The aim of this study was to evaluate the role of sham feeding in postprandial changes of gastric myoelectrical activity. Eighteen asymptomatic healthy volunteers (10 men, 8 women; mean age: 31), with no history of gastrointestinal disease were studied. Gastric myoelectrical activity was recorded for 30 min at baseline, 30 min after sham feeding, and 1 hr after eating, using surface electrogastrography. The electrogastrogram (EGG) was analyzed by spectral analysis. It was found that the changes of postprandial EGG parameters were significantly correlated with those after sham feeding (EGG dominant power: r = 0.6, P < 0.01; dominant frequency: r = 0.8, P < 0.001; percentage of regular slow waves: r = 0.7, P < 0.003). We concluded that intrinsic gastric electrical activity can be altered by sham feeding and the cephalic phase of digestion plays an important role in the postprandial response of gastric myoelectrical activity.

Adult↗