Glucagon,gastric inhibitory polypeptide and the gastrocolic response

Serosal bipolar electrodes and strain gauge force transducers were placed on the right and left colon in subhuman primates to record spike discharges and circular muscular contractions. The effect of glucagon on colonic motor and electrical activity were studied before and after meals. Serum concentration of gastric inhibitory polypeptide was measured simultaneously 15 minutes before and 45 minutes after eating. Serum levels of gastric inhibitory polypeptide increased in response to eating; pre- and postcibal concentrations were not altered by glucagon. The gastrocolic response of the colon to eating was demonstrated. Glucagon inhibited the intrinsic activity of the entire colon before meals and partly inhibited the right colon after meals. Postcibal left colon activity was not inhibited by glucagon. This indicates that a distinct mechanism accounts for the left colonic postcibal increase in contractile and electrical spike activity. A neural or humoral mechanism is implicated but is not specifically identified.     

The gastrocolic response: Is it gip?

Previous experiments demonstrated that feeding is followed by increased electrical spike discharges and contractions of colon smooth muscle. This gastrocolic response has a definite lag period before onset, and is not due to distention of the colon by food. In these experiments, the possible association between altered serum concentration of certain gastrointestinal hormones and the gastrocolic response was investigated in eight stump-tailed monkeys. The animals had extraluminal miniature strain gauge force transducers and bipolar silver electrodes applied in pairs to the serosal surface of the cecum, ascending colon, and transverse colon to record contractions of circular muscle and electrical spike discharge potentials. The serum concentrations of gastrin, cholecystokinin, and gastric inhibitory polypeptide were measured by radioimmunoassay, and the contractile responses of the bowel were recorded, before and after presentation to fasted animals in random order of a dry meal, a wet saline meal, a wet magnesium sulfate meal, or a continued fast. The dry meal was associated with an increase in frequency of electrical spike discharges and contractions of circular colon muscle, as well as an increase in the serum concentration of gastric inhibitory polypeptide, both events occurring 15–60 min after beginning the meal. Other meals had no effect on colon motility or serum gastric inhibitory polypeptide concentration. Serum gastrin and cholecystokinin concentrations were unchanged by all experimental manipulations. This evidence supports our hypothesis that the gastrocolic response has an hormonal basis.     

Postoperative ileus: a colonic problem?

Postoperative electromechanical activity of the gastric antrum, small bowel, right colon, and sigmoid colon was recorded in stumptail monkeys in response to retroperitoneal dissection and transient clamping of the renal pedicle. Bipolar silver electrodes and extraluminal bonded strain gauge transducers were used to record slow-wave and spike discharges and contractions of intestinal smooth muscle. After operation myoelectric activity was decreased transiently in the antrum and for only a few hours in the small bowel. Right colon contractile activity was decreased significantly for 24 hours and that of the sigmoid colon for 72 hours. Postoperative inhibition of bowel motility appears to be most profound and persistent in the colon.     

Acetylcholine-related bowel dysmotility in homozygous mutant NCX/HOX11L.1-deficient (NCX-/-) mice-evidence that acetylcholine is implicated in causing intestinal neuronal dysplasia

Background/purpose

Homozygous mutant Ncx/Hox11L.1-deficient (Ncx−/−) mice develop mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors investigated the mechanism of intestinal dysmotility in these mice.

Methods

Five-week-old Ncx−/− mice with mega ICC were compared with age-matched BDF1 control mice. Jejunum, ileum, and colon were excised from all mice and 1.0-cm-long strips of each organ, each with a resting tension of 0.5g, were suspended in an organ bath filled with Tyrode’s solution at 37°C and bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Contractile responses to acetylcholine chloride (ACh), histamine, serotonin, and barium chloride (BaCl₂) were recorded isometrically.

Results

For ACh, Ncx−/− mice had decreased distal colon circular muscle contraction only at lower doses and decreased distal colon longitudinal muscle contraction for all doses compared with controls (P < .05 or P < .01). In the proximal colon, Ncx−/− mice had increased circular muscle contraction only at higher doses and decreased longitudinal muscle contraction only at lower doses compared with controls (P < .01 or P < .05). ACh did not affect jejunum, and there were no significant effects on ileum. There was no response to histamine and serotonin by any part of the bowel, and the response to BaCl₂ was the same for both Ncx−/− mice and controls.

Conclusions

Only ACh differentially affected muscle contraction in Ncx−/− mice in the proximal and distal colon. Thus, ACh is implicated in causing the bowel dysmotility seen in Ncx−/− mice and human IND.     

The mechanism of intestinal motility in homozygous mutant Ncx/Hox11L.1-deficient mice--a model for intestinal neuronal dysplasia

Purpose

Homozygous mutant Ncx/Hox11L.1-deficient (Ncx−/−) mice develop mega-ileo-ceco-colon with a caliber change in the proximal colon. This study investigated the mechanism of intestinal motility in these mice.

Method

Five-week-old male and female Ncx−/− mice with mega-ileo-ceco-colon (n = 8) were compared with age-matched male BDF1 mice used as controls (n = 8). All mice were sacrificed, and uniform-sized strips of jejunum, ileum, proximal colon, and distal colon were exposed to electrical field stimulation and pretreatment with atropine sulfate, guanethidine, or tetrodotoxin. Contractile responses were recorded and compared.

Results

Longitudinal muscle from strips of jejunum and ileum from all mice (BDF1 and Ncx−/−) did not respond to electrical field stimulation, whereas ileal circular muscle contracted in BDF1 mice and contracted and relaxed in Ncx−/− mice. Pretreatment with atropine sulfate and guanethidine inhibited the responses of circular muscle of distal colon and ileum in BDF1 mice significantly (P < .05), but no effect was observed in Ncx−/− mice.

Conclusion

In ileum, BDF1 mice have cholinergic and adrenergic dominant contraction patterns, whereas Ncx−/− mice have relaxation-dominant patterns because of nonadrenergic, noncholinergic nerves. Based on this, there would appear to be some kind of variation in the gastrointestinal nerve supply in Ncx−/− mice.     

Effect of whole gut irrigation solutions on gastrointestinal smooth muscle activity

Background/Purpose

It has been suggested that whole gut irrigation (WGI), which is a preparation method for large bowel surgery or colonoscopy, increases gastrointestinal motility by creating a gastrocolic reflex. An experimental study was performed to evaluate the effect of different WGI solutions on gastrointestinal smooth muscle activity.

Materials and Methods

Thirty Wistar albino rats weighing 200 to 250 g were enrolled in the study. After anesthetization with thiopental sodium (50 mg/kg), proximal ileum, terminal ileum, and colon segments were removed via median laparotomy to obtain a control group. Four different groups (n = 6) were designated as having WGI with saline solution (SS), lactated Ringer's solution (RL), polyethylene glycol (PEG), and dibasic sodium phosphate (DNP). Bowel cleaning was performed by infusing solutions at a rate of 2 mL/min via gastric tube, until the stool was cleared. After completing the bowel cleaning, 2 cm of tissues were removed and suspended in Tyrode solution in an isolated organ bath with a resting tension of 1 g, to obtain carbachol and potassium chloride (KCl) responses.

Results

The mean bowel cleaning times were 87.5 ± 9.35, 81.6 ± 9.83, 86.6 ± 11.6, and 85.0 ± 0.0 minutes in SS, RL, PEG, and DNP groups, respectively. The total amounts of solutions needed for cleaning were 156.67 ± 21.6, 195.0 ± 20.0, 197.5 ± 32.8, and 70.0 ± 0.0 mL, respectively. Although there was no difference in cleaning time between the groups, the amount of solution required was significantly less in the DNP group (P = .02). In the proximal ileum segments, though there was no difference in carbachol responses between groups, KCl responses were significantly increased in the RL group (P < .05). When we evaluated the terminal ileum responses, carbachol responses were significantly increased in RL and PEG groups (P = .011) and decreased in the DNP group (P = .049). The KCl responses were also significantly increased in the RL group with respect to the other groups (P < .05). Colon segments showed no difference in contractile responses with respect to different WGI solutions (P > .05, analysis of variance, post hoc Dunn's test).

Conclusion

The different WGI solutions demonstrated no significant differences in colon contractions. The increased contractile responses in the proximal and terminal ileum segments after WGI with RL may be related to the electrolyte composition of RL. Although the lower amount of DNP solution required to achieve bowel cleaning seems to be an advantage, the decreased ileal contractions can be assessed as a disadvantage of DNP irrigations.     

Evaluation of the longitudinal musculature of segments of the distal colon interposed following extended jejunum-ileum resection

Several morbid conditions may necessitate extensive intestinal resection, leading to short-bowel syndrome. When clinical treatment becomes inefficient, a surgical approach is necessary. Distal colon interposition is one of the viable techniques. The interposition of colon segments between remnants of the small bowel improved lifestyle, increased transit time, and diminished diarrhea. The aim of this study is to observe the longitudinal muscular contractions after distal colon interposition. Sixteen male Wistar rats (EPM-1) were submitted to an 80% small bowel resection associated with a partial colectomy of the distal colon immediately after the bifurcation of the middle colic artery followed by a 3-cm isoperistaltic distal colon interposition. After 70 days, the animals were submitted to euthanasia and segments of the jejunum, ileum, remnant colon, and interposed colon were prepared for pharmacological tests. The isometric contractions were measured by a polygraph. After 30 minutes, the dose/effect curves were obtained for both metacholine and barium chloride stimulation through the extraluminal surface (serosa). After this period, we observed a significant increase in the length, diameter, and thickness of the intestinal wall. Regarding the sensibility (pD(2)), no difference was found (interposed colon = 7.21 +/- 0.2; remnant colon = 7.65 +/- 0.1; remnant jejunum 7.46 +/- 0.1; and remnant ileum 7.57 +/- 0.1), even though the animals were submitted to different procedures. In relation to the maximal effect (E(max)), the longitudinal muscle contraction responses (interposed colon = 11.79 +/- 0.1; remnant jejunum = 15.42 +/- 0.2; and remnant ileum = 11.48 +/- 0.2) were lower than those of the remnant colon (E(max) = 22.42 +/- 0.1). This means that there was a possible adaptation of colonic segments to their new location.     

Inhibition of ileal and colonic ornithine decarboxylase activity by alpha-difluoromethylornithine in rats: transient atrophic changes and loss of postresectional adaptive growth

To determine the role of putrescine synthesis in adaptive hyperplasia of the ileum and colon, DL-alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC), the enzyme controlling putrescine biosynthesis, was fed to rats after excision of the proximal half of the small bowel. A rise in ODC activity (280% in the proximal ileum, 62% in the proximal colon) and a rise in putrescine content (220% in the proximal ileum, 250% in the proximal colon) normally accompanied characteristic cytochemical adaptive increases in the ileum and colon at day 6. Inclusion of 1% DFMO (2.1 gm/kg/day) in drinking water for 12 hours before operation and for 14 days thereafter decreased ODC activity by 85% to 96%, reduced levels of putrescine and spermidine and measurements of the adaptive response by 50% in the ileum, and abolished the adaptive response in the colon. During the first 10 days of DFMO feeding, villous atrophy and other hypoplastic changes occurred in control rats, but by 14 days of DFMO feeding atrophy and hypoplasia were no longer present. Although DFMO inhibits adaptive hyperplasia occurring in the ileum and colon of rats after resection of the proximal half of the small bowel, spontaneous recovery of villous atrophy occurs during further DFMO feeding and may protect the host during chemotherapy.     

Intestinal motility changes in experimental large bowel obstruction

Bipolar electrodes for recording electrical discharges of colon smooth muscle and strain gages for recording associated contractions of circular muscle were implanted in six rhesus monkeys. After recovery, baseline records were made. The animals then had an obstruction device implanted in sigmoid colon which resulted in progressive compromise of the lumen terminating in complete obstruction after 13 +/- 2 days. Recording were made daily during development of obstruction. As obstruction became more complete, contraction frequency decreased in right colon, increased in left colon proximal to the obstruction, and was unchanged in left colon distal to the obstruction. The frequency of distentions increased in colon proximal to the obstruction but was unchanged distally. Simultaneous mass actions, a complex of nonperistaltic high amplitude contractions and distentions occurring nearly simultaneously throughout the colon which is not seen in normal colon, appeared in colon both proximal and distal to the obstruction and became more frequent as the degree of obstruction progressed. Colon obstruction results in abnormal motility complexes, but not in hyperperistalsis. Mass actions probably are the basis for colic and rushing bowel sounds noted clinically in colon obstruction.     

Vasoactive intestinal polypeptide potentiates the hypoxemia-induced decrease in splanchnic circulation in the rat

The effects of acute infusion of vasoactive intestinal polypeptide (VIP) and hypoxemia on splanchnic circulation were examined in 35 awake Sprague-Dawley rats. Indwelling catheters were placed in the superior vena cava and the proximal aorta via the internal jugular vein and internal carotid artery, respectively, while the rats were under ether anesthesia. Four hours later, when the rats were awake and active, VIP (molecular lot 3226) was infused intraarterially for 30 minutes. The distribution of cardiac output was measured at the end of VIP infusion using 125I-labeled microspheres. VIP was administered at a low (1.5 ng/min) and a high infusion rate (44.1 ng/min) for 30 minutes. The effect of hypoxemia on circulatory response to VIP was examined only in the high VIP infusion group, by placing the rat in a 10% oxygen environment. Appropriate control experiments were performed with each group. The high-dose VIP resulted in a marked reduction in distribution of cardiac output to the splanchnic circulation. This effect was potentiated by hypoxemia, particularly in the distal ileum and colon. The metabolic clearance rate of VIP increased with the rate of VIP infusion and was decreased by hypoxemia. It was concluded that only in high concentration does VIP have any effect on splanchnic circulation. However, in the presence of hypoxemia, VIP may have an important role in cardiovascular compensatory response and may contribute to the development of ischemic bowel injury.     

Comparison of the myoelectrical activity of the lateral and J-shaped ileal reservoirs

Ileal myoelectrical activity was studied in ten 10-cm J-shaped and ten lateral ileal reservoirs (IR) in rabbits. Electrodes and a strain gauge were placed on both ileal segments of the reservoirs as well as the proximal and distal ileum entering and leaving the reservoirs. In three additional rabbits without reservoirs (controls), electrodes and a strain gauge were sutured to the distal ileum in a similar manner. Myoelectrical activity was recorded as (1) short spike burst complexes (SSBC) lasting greater than 25 seconds but less than three minutes, and (2) long spike burst complexes (LSBC) lasting more than three minutes. SSBC propagated through the lateral IR two weeks after its construction and were synchronous with intestinal contraction. In contrast, SSBC did not become organized or propagate distally through the J-shaped IR until eight weeks after reservoir construction. LSBC occurred infrequently in control rabbits and in those after construction of the J-shaped and lateral IRs. Propagation of LSBC in control rabbits was synchronous with prolonged propulsive intestinal contraction. In both the J-shaped and lateral reservoirs, LSBC occurred randomly and did not propagate from proximal to distal ileum through the IR until three months after reservoir construction. The frequency and duration of LSBC remained diminished for the J-shaped IR at three months when compared with the lateral IR. It is concluded that the return of normal propulsive activity occurs earlier in the lateral iso-peristaltic IR than in the J-shaped IR but that both are effective at three months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analyses of small bowel propulsion, ileo-caecal passage and serum gastrin after truncal vagotomy. A methodological study in the rat with continuous intraduodenal infusion.

A test substance containing 51CrO--4 was administered to the duodenum of vagotomized or sham-operated, conscious rats for 5 hours at a rate of 3.3 mul/min. The distribution of 51Cr in the stomach, small bowel, caecum and colon was measured with a scintillation counter. Data reduction was made with automatic methods. The activity distribution in the small bowel was found to be irregular. A transit time of about 3 hours was observed between the duodenum and the caecum. The proximal 40% of the small bowel was passed in about 30 min at a constant rate. No differences between vaotomized animals and controls could be demonstrated. The passage from ileum to caecum in vagotomized animals indicated a process, with constant portions, each discharge containing about 11% of the total administered activity, implying two discharges per hour.     

The effect of raising the concentration of potassium in the blood or intestinal lumen on the transport of potassium in the dog intestine.

The rates of transport of potassium, sodium and water across the intestinal mucosa of Thiry-Vella fistulas of colon and ileum, were studied in dogs in two experimental situations; (1) following intravenous infusion of potassium (15 mEg) over 30 minutes and (2) during variations in the intraluminal concentration of potassium in the range 0.8-16.0 mEg/l. Following intravenous infusion of potassium the rates of potassium secretion into the colon were usually increased; the rates of sodium and water absorption were either unchanged or decreased. The unidirectional rate of movement of potassium into the lumen increased as the concentration difference across the mucosa increased; the movement of potassium in the opposite direction remained relatively constant. The undirectional movement of sodium and water into the lumen of the colon also increased but to a lesser extent. The effect on potassium transport in the ileum was not so marked. With increase in the intraluminal concentration of potassium there was a decrease in the rate of net potassium secretion in both colon and ileum. The rates of net absorption of sodium and water were not significantly altered. Unidirectional potassium movement into the body increased in all the ileal fistulas.     

Motility changes associated with large bowel obstruction and its surgical relief

Strain gauges and electrodes to detect intestinal motility were attached to the terminal ileum, right and left sides of the colon in Rhesus monkeys. Baseline recordings were made. An obstruction device was applied to the left colon at a laparotomy. Compromise of the bowel lumen leading to total obstruction occurred at 13 +/- 2 days. As obstruction progressed, contractions decreased in the terminal ileum and right colon but increased in the left colon proximal to the obstruction. Distention wave forms increased in the colon proximal to the obstruction. Visible intestinal movement, borborygmi and signs suggesting colic were accompanied by a motility phenomenon, simultaneous mass actions, not seen in normal unobstructed bowel. The obstructed segment was resected and an anastomosis made. The motility recordings revealed that postoperative ileus persisted for less than 48 hours and motility returned to normal significantly earlier than after a control laparotomy.     

Effects of cisapride on the motility of the digestive tract in dogs and guinea pigs

Effects of cisapride on the motility of the digestive tract in vivo in dogs and the guinea-pig intestine in vitro were studied. Cisapride (0.05-2.0 mg/kg, i.v.) produced an increase in amplitude of spontaneous contractions and basal tone in the stomach, duodenum, jejunum and proximal and distal colon in dogs. In some animals, however, it induced an inhibition with decrease in amplitude and tone. It also induced an increase in amplitude of contractions in the gallbladder and the sphincter of Oddi in dogs. The tone of the gallbladder was elevated by the same dose of cisapride, but the tone of the sphincter of Oddi was decreased. The drug produced a reverse response in some animals. These excitatory responses to cisapride were abolished by atropine (0.2 mg/kg, i.v.). Motility of the guinea-pig isolated ileum and colon was enhanced with an increase in their amplitude of contractions and basal tone at low concentrations of cisapride (10(-9)-10(-6)M) but it was inhibited at higher concentrations (10(-5)-10(-4)M). Atropine abolished the excitatory response of the ileum to cisapride in all cases. It abolished the excitation of the colon in some preparations but reduced only in some degree in the other. The inhibitory effect of cisapride on isolated preparations was unaffected by tetrodotoxin. From these results, it is concluded that cisapride enhances motility of the gastrointestinal tract and biliary tract by acting on myenteric cholinergic neurons and inhibits it by acting on the smooth muscle itself.     

DOES THE COLON ADOPT SMALL BOWEL FEATURES IN A SMALL BOWEL ENVIRONMENT?

Background: Isoperistaltic colon interposition is one of several surgical options available in the treatment of short bowel syndrome. It functions primarily by slowing the rapid intestinal transit that follows small bowel resection (SBR). Previous studies have interposed distal colonic segments and although there is evidence of adaptation by the interposed colon it is not known whether these segments develop histologic or functional small bowel characteristics. Methods: In this study evidence was sought of metaplasia in the interposed segments after 80% SBR and, because proximal colon is a midgut derivative, the differences between proximal and distal colonic segments were examined. Results: There was no qualitative histological evidence of metaplasia by the interposed segments. There was a significant increase in crypt depth, mucosal thickness and maltase concentration of the interposed segments compared with the non-transposed colon of the controls. The maltase concentations were increased to the extent that they were not significantly different from the concentration present in normal ileum. Conclusions: Although there was no gross evidence of small bowel intestinalization by the interposed segments, there was evidence of adaptation which was not merely an extension of the adaptive process seen after SBR alone. These changes resulted in the colon taking on some small bowel features. There was no significant difference between proximal vs distal interposed segments.     

The effect of small bowel bypass and subsequent resection on gastric acid secretion and serum gastrin

Evaluation of gastric acid secretion and serum gastrin response to proximal or distal intestinal bypass and subsequent resection was undertaken. Ten dogs with gastric fistulas underwent control secretory studies consisting of basal acid output (BAO), maximal vagal stimulation (2 deoxy-d-glucose (2DG) 150 mg/kg iv), maximal histamine stimulation (160 μg/kg/hr iv), and test meal stimuli. Serum gastrin was measured basally and following gastric stimulation. Dogs were then divided into two bypass groups: Group I, distal bypass, leaving 40 cm jejunum and 4 cm ileum; and Group II, proximal bypass, leaving 4 cm jejunum and 40 cm ileum. Postoperatively, repeat studies were performed. Both groups then underwent resection of the bypassed segments followed by repeat secretory and gastrin tests. BAO was significantly increased in Group I dogs. BAO increased from a control of 0.04 ± 0.02 to 0.51 ± 0.19 meq H⁺/60 min (±SEM). No significant changes in BAO were observed in Group II following bypass. Acid secretion to maximal vagal or maximal histamine stimulation was not significantly different in either group. Serum gastrin response was unchanged in either group following a test meal. In Group I dogs, resection of the previously bypassed bowel produced a further significant increase in BAO (1.44 ± 0.4 meq H⁺/60 min). After resection of the bypassed bowel, there was no significant change in basal or stimulated gastrin. Gastric fistula BAO increased following 90% distal but not proximal bypass; subsequent resection of the bypassed segment produced a further increase in BAO. Acid secretory responses to both histamine and 2DG were not influenced by either bypass or resection. An increase in BAO without a change in the background of serum gastrin may suggest the presence of a gastric secretory inhibitor in the distal small bowel.     

Gastric emptying in children with gastroesophageal reflux. I. An estimate of effective gastric emptying

The association of gastroesophageal reflux (GER) and gastric emptying has been observed, but its importance is poorly understood. We compared 18- to 24-hour esophageal pH recordings with gastric emptying of radionuclide in apple juice in 109 children (2 weeks to 16 years old) referred for an evaluation of GER. A pH score and the pattern of GER (type I, II, and III) were obtained by esophageal pH monitoring. Gastric emptying was measured at 30 minutes (%GE30) and at 60 minutes (%GE60). The measured gastric emptying of apple juice was similar for the normal child and for those with GER regardless of pattern type. An inverse linear correlation between postcibal reflex and measured gastric emptying was demonstrated only by the eight asymptomatic children with a normal pH score (%GE30, r = -.9603, P less than .001; and %GE60, r = -.8263, P less than .05). If the contribution of postcibal reflux on gastric emptying was eliminated, then the effective gastric emptying was increased in many children with the type I (44%, P less than .05), type II (46%, P less than .05), or type III (60%, P less than .05) pattern of GER as compared with children with a normal reflux pattern (7%). In conclusion, measured gastric emptying of clear liquids is not necessarily decreased in most children with GER. Furthermore, many children with GER demonstrate an increased effective gastric emptying even though measured gastric emptying may not appear increased.     

Polyethylene glycol rapidly restores physiological functions in damaged sciatic nerves of guinea pigs

OBJECTIVE: We have studied the ability of the hydrophilic polymer polyethylene glycol (PEG) to anatomically and physiologically reconnect damaged axons of the adult guinea pig spinal cord. Here we have extended this approach to test whether completely severed guinea pig sciatic nerves in isolation could be fused and whether PEG was able to repair severe standardized crush injuries to sciatic nerves in vivo. METHODS: The fusion test was performed with isolated sciatic nerves maintained in a double-sucrose gap recording chamber. For in vivo experiments, the sciatic nerve was surgically exposed in the hind leg of deeply anesthetized adult guinea pigs and was crushed proximal to its insertion in the gastrocnemius muscle. PEG was injected just beneath the epineurium with a 29-gauge needle, allowed to remain in the damaged axon region for 2 minutes, and removed. Sham-treated guinea pigs received an injection of water or Krebs' solution. Three indices of recovery were simultaneously monitored in response to electrical stimulation of the proximal nerve, i.e., 1) recovery of compound muscle action potentials (in millivolts), 2) contraction force of the muscle (in dynes), and 3) displacement of the muscle (in millimeters). RESULTS: When isolated sciatic nerves were severed within the double-sucrose gap chamber, compound action potential propagation through the transection plane was eliminated. After abutment of the two segments and 2-minute PEG application to this site, variable compound action potential recovery was measured in all four cases. The crush injuries to the sciatic nerve in vivo eliminated the three functional responses to sciatic nerve stimulation in all animals. Within the first 30 minutes after treatment, only 1 of 12 control animals exhibited spontaneous recovery in any of these measures, compared with six of eight PEG-treated animals. By 45 minutes, two more sham-treated animals and one more PEG-treated animal had recovered at least one functional response. This difference in proportions between PEG-treated and sham-treated animals was statistically significant (P < or =0.02). CONCLUSION: We conclude that these preliminary data suggest that PEG application may be a way to interfere with the steady dissolution of peripheral nerve fibers after mechanical damage and to even functionally fuse or reconnect severed proximal and distal segments.     

Characterization of the spontaneous electrical and contractile activity of smooth muscle cells in the rat upper urinary tract.

PURPOSE: We morphologically and electrophysiologically identified the cells that generate the electrical activity underlying the peristaltic contractions of the rat upper urinary tract. MATERIALS AND METHODS: Electron microscopy and tension recording techniques were used to characterize the smooth muscle cells underlying spontaneous contractions in the wall of the rat ureter, and proximal and distal renal pelvis. Intracellular microelectrodes, containing 4% neurobiotin were used to record data from the cells of the renal pelvis, which were later viewed on a confocal microscope. RESULTS: Spontaneous myogenic contractions (average 22.3 +/- 2.2 minutes(-1)) originated in the proximal renal pelvis and propagated into the distal renal pelvis and ureter in 6 preparations. Smooth muscle cells in the renal pelvis and ureter were typical in appearance with greater than 85% of their sectional area containing clumped contractile filaments. In contrast, contractile fibrils occupied only 65% of the sectional area of the smooth muscle cells within the most proximal region of the renal pelvis (pelvicaliceal junction). In strips of the renal pelvis spindle shaped cells 83 to 200 microm. long fired spontaneous action potentials (6 minutes(-1)) consisting of an initial spike, a quiescent plateau phase and abrupt hyperpolarization to a peak diastolic potential of -60 mV. Other spindle shaped cells 94 to 112 microm. long displayed small membrane transients (15 minutes(-1)) 9 to 19 mV. in amplitude, firing from a diastolic potential of -40 mV. CONCLUSIONS: It is likely that the spontaneous contractile activity of the rat upper urinary tract arises from the discharge of action potentials in typical smooth muscle cells of the proximal renal pelvis that are directly driven by the spontaneous membrane oscillations of atypical smooth muscle cells.