The effects of baclofen on the feeding behaviour and body weight of vagally stimulated rats.

UNLABELLED: It is hypothesised that the GABA(B) receptor agonist baclofen increases or has no effect on food intake, and electrical stimulation of vagal nerves decreases food intake. The aim of this study was to evaluate the effects of baclofen in vagally stimulated rats. MATERIAL AND METHODS: Thirty two Wistar rats were divided into five groups: group A scheduled for microchip implantation for vagal stimulation, group B for sham operation, group C for microchip implantation and baclofen medication, group D for baclofen medication only and group E for gastric motility evaluation under influence of baclofen. The following parameters were then evaluated: food intake and body mass, gastric motility, leptin, insulin, and glucose serum levels. RESULTS: In the comparison of groups B and A, daily food intake and body weight gain decreased by 17% (p<0.05) and by 22% (p<0.05), respectively. Baclofen alone (group D) did not significantly change either food intake nor diurnal body weight compared to the controls, but when used in conjunction with the microchip (group C) it did significantly reduce effect of vagal neuromodulation (p<0.05). Furthermore, a significant decrease in leptin and glucose levels was detected in group C: 677 to 165 pg/ml (p<0.05) and 5,93 to 4,88 mmol/l (p<0.05), respectively. The administration of baclofen stimulated significantly gastric motility and elicited irregular motor migrating complex (327+/-200 against control 255+/-52 cmH2O/s). CONCLUSIONS: These results suggest that microchip vagal neuromodulation through increased vagal afferent activity induces an alteration in the feeding behaviour and decreases nocturnal food intake and body weight. These effects were partially attenuated by baclofen. The data suggests that GABA(B) receptors play an important role in the pathomechanism of attenuation of food intake induced by vagal nerve stimulation.

Encoding meal in integrated vagal afferent discharge.

Vagal afferents are integral part of the negative feedback loop induced by constitution and size of food stomach and jejunum. Aim of this study was to assess vagal discharge in response to food and gastric distension in rats. Electrophysiological recordings of vagal afferents in fasted (n=32), fed rats (n=20) and during gastric balloon distension (n=12) were performed. After 60 minutes of fasted nerve recording tube feeding was done. Fasted rats also underwent gastric distension via oesophagus. Vagal afferents discharges were analysed with dual time-amplitude window discriminator. Total vagal afferent discharge in fasted and fed rats revealed 0.3 +/- 0.12 vs 0.56 +/- 0.22 Hz (p<0.05). We observed two distinct discharge patterns: high amplitude low frequency (HALF) and low amplitude high frequency (LAHF). HALF spikes were observed more frequent in fasted than in fed rats (0.05 +/- 0.02 vs. 0.03 +/- 0.016 Hz (p<0.05). Conversely LAHF spikes in fed rats predominated over their occurrence in fasted rats: 0.52 +/- 0.2 vs. 0.25 +/- 0.12 Hz (p<0.05). Left vagal afferents discharge rises with gastric distension of 6, 8 and 10 ml and were: 0.46 +/- 0.22 Hz, 0.65 +/- 0.31 Hz, 0.86 +/- 0.33 Hz (p<0.05) respectively. Similar discharge showed right vagal afferents: 0.41 +/- 0.08 Hz, 0.51 +/- 0.13 Hz and 0.77 +/- 0.27 Hz (p<0.05) for 6, 8 and 10 ml of distension, respectively. We conclude that interdigestive information from gastrointestinal tract is encoded in high amplitude low frequency of spikes pattern in the vagus nerves.

Capasaicin induced deafferentation enhances the effect of electrical vagal nerve stimulation on food intake and body mass.

Study was based on hypothesis that electrical stimulation (ES) with parameters obtained from analysis of vagal afferent discharge fed state may fake brain with satiety state. We evaluated effect of denervation of vagal capsaicin-sensitive afferents on food intake and body weight in rats with ES of vagal nerves using microchip (MC). Group A was scheduled to MC implantation, B to sham operation only, C to MC implantation and capsaicin vagal deafferentation, and D to capsaicin denervation only. ES lasted 24 days. MC parameters were 0.05 Hz, 0.1s, 0.55 V. ES of left vagus significantly reduced total food intake as well as the mean daily intake in groups A and C in comparison to control and D group (ANOVA, F=18.55, p=0.0038). Body weight was lower in group A (3462 g) and C (2727 g) then in control (3814 g) and D (3568 g) (F=25.68, p=0.00068). Leptin decreased in C (165 pg/mL) in comparison to A (625 pg/mL), B (677 pg/mL), and D (612 pg/mL) (p<0,05), mainly due to ES (F=7.27, p=0.019). Glucose was decreased in A (F=5.55, p=0.036) - by 11% and by 16% in C group. Proper vagal neuromodulation results in central and peripheral effects causing food intake and body weight downregulation.

The effect of transcutaneous nerve stimulation (TENS) on gastric electrical activity.

UNLABELLED: TENS became widely accepted method of treatment pain syndromes in clinical practice. Lately has been shown that its affects also gastrointestinal tract by releasing NANC neurotransmitter VIP. The aim of this study was to evaluate the effects of TENS on gastric myoelectric activities measured by electrogastrography (EGG). Eighteen healthy men (mean age 23 +/- 1.7) were included in the study. Healthy volunteers were divided on 3 groups each 6 persons: with normogastria occurring at 94.5 +/- 7% of recording time--group A, with predominant bradygastria (36.6 +/- 14%)--group B and with tachygastria (33 +/- 14%)--group C. In fasted condition EGG (Synectics, Sweden) was recorded with skin electrodes. TENS 15 min was performed with use of Sinus 5 stimulator (6 Hz, 0.1 ms duration, intensities 10-20 mA, Zimmer, Germany). Stimulating electrodes were placed on non-dominant hand. RESULTS: None of the subjects during TENS reported any side effects or symptoms, during the all studies. In group A in the fasting recordings, after TENS, an decrease of the normal values in the range 2-4 cpm down to 78.5 +/- 21% of recording time (p = 0.03) occurred. The dominant frequency in the bradygastric region increased up to 17.7 +/- 7% of the total recording. In group B TENS decreased bradygastria level from 36.6 +/- 14% to 20.6 +/- 15% (p = 0.02). TENS did not significantly affect tachygastria in group C. Amplitude of the EGG signal after TENS in group B and C increased by 40 and 150% respectively (p < 0.05). Significant decrease of the amplitude was observed in group A (13%). We conclude that TENS by activating centrally mediated somato-visceral reflexes affects gastric electrical activity. Our results suggest that TENS may be useful in treatment of the gastric dysrhythmia.

Effects of vagal neuromodulation and vagotomy on control of food intake and body weight in rats.

Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.

Effects of continuous microchip (MC) vagal neuromodulation on gastrointestinal function in rats.

Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250-350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5-30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 +/- 2.5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid--intragastrically) almost doubled amount of bursts to 12 +/- 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 +/- 4.8 vs control 35.5 +/- 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 +/- 9.08 vs control 23.56 +/- 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 +/- 9.3 vs control 98.5 +/- 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 +/- 0.8 vs 1.17 +/- 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 +/- 0.35 vs 0.68 +/- 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 +/- 0.14 vs 0.14 +/- 0.12 mmol/30 min, p < 0.05) but MAO did not change in MC rats (0.37 +/- 0.25 vs 0.42 +/- 0.28 mmol/30 min, p 0.05). Gastric emptying of isotonic solution increased by 10% (90.46 +/- 5.34 vs 80.39 +/- 9.95) percent of marker passing to duodenum/5 min, p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight.

Role of prostaglandins in alkaline secretion from the gastroduodenal mucosa exposed to acid and taurocholate.

Gastroduodenal mucosa produces alkaline secretion (AS) that is several times greater in the duodenum, particularly in its proximal part, than in the fundic or antral portions of the stomach. Exogenous prostaglandins (PGs) of E and F but not of I series are capable of augmenting AS. Similar stimulatory effects on AS were observed after topical administration of arachidonic acid and HCl solution. Endogenous PGs appear to mediate this AS as their release from the mucosa is increased upon exposure to arachidonic acid and the pretreatment with indomethacin reduced the alkaline response to arachidonic acid and HCl. Taurocholate-induced alkaline response is probably due to increased mucosal permeation for HCO3 as it was accompanied by a decrease in PD value and indomethacin failed to affect this response.

Immediate effects of endoscopic sphincterotomy on sphincter of Oddi motility.

The evidence exists that incomplete sphincterotomy in patients with biliary tract diseases may result in early symptoms reoccurrence or lack of improvement. Sphincter of Oddi manometry (SOM) can be used to verify the completeness of the procedure. The purpose of the study was to investigate the immediate effects of biliary endoscopic sphincterotomy (BES) and common bile duct stones (CBDS) clearance on biliary sphincter of Oddi (SO) motility. Moreover the percentage of incomplete sphincterotomies was estimated. 26 patients (6 male, 20 female, 24-93 years) with confirmed choledocholithiasis were investigated. All underwent BES followed by CBDS extraction, and then SO manometry (SOM) was performed. Moreover 6 patients underwent SOM prior to BES. SOM was performed with a triple lumen 5 Fr catheter attached to the water perfused low compliance system. Immediately after sphincterotomy and extraction of the CBDS common bile duct pressure dropped from a mean of 10.9 mmHg to 2.9 mmHg (p < 0.05). Similarly basal biliary sphincter pressure decreased from 22.7 mmHg to 7.3 mmHg (p < 0.05). 20 patients presented duodeno-choledochal gradient of less than 5 mmHg. However only 10 patients had also basal sphincter pressure lower than 5 mmHg. The phasic sphincter activity was abolished in 16 patients, whereas phasic contractions persisted in 10 patients. Seven patients displayed uncoordinated, low amplitude contractility. BES significantly decreases SO and CBD pressures, but when performed for CBDS extraction, commonly does not abolish SO motor activity nor ablate choledocho-duodenal gradient. Therefore to confirm the completeness of sphincterotomy, SO manometry is recommended.

The effect of the year angiotensin-converting enzyme inhibitors (ACE I) intake on circadian heart rate variability in patients with primary hypertension.

INTRODUCTION: The autonomic nervous system (ANS) disturbances have been considered as one of the important factors in development of essential hypertension. However information about the effect of antyhypertensive treatment (angiotensin-converting enzyme inhibitors--ACEI) on cardiac ANS activity is ccscarce. AIM: The purpose of the study was to evaluate the HRV circadian changes in patients with essential hypertension, treated with ACEI throughout the period of one year. METHODS: Ten patients with essential hypertension, aged 26 to 64 years (mean 54.3 +/- 12.3) and 10 healthy volunteers, matched for age and gender were qualified for the investigation. Twenty four-hour arterial blood pressure measurements with simultaneous ECG monitoring were conducted in both mentioned groups. The hypertensive patients were examined before and after 1 year of ACE inhibitor (enalapril) intake. HRV analysis was carried out by the fast Fourier transformation (FFT). The time and spectral parameters were compared in 8 examined subjects characteristic for dippers, in time periods of day (6 a.m.-10 p.m.) and night (10 p.m.-6 a.m.). RESULTS: The results obtained before the treatment, likewise in control group, presented night's increases of RMSSD (p < 0.05), pNN50 (NS, p > 0.05), VLF, LF (p < 0.05) and HF (NS) mean values with a decrease of LF/HF ratio (p < 0.05). Similar tendencies in the cardiac ANS activity were observed after 1 year of the enalapril intake. A comparison of day's HRV before and after one year of the ACE inhibition presented the increase in values of the parasympathetic system reflecting parameters: RMSSD, pNN50 (p = 0.01) and HF (NS) with a decrease of LF/HF ratio (p < 0.01). The evaluation of the night's HRV parameters presented the increase of HF mean value (p < 0.05), without any other significant changes between the trials. CONCLUSIONS: After 1-year of ACE inhibitor administration the only improvement of the day's parasympathetic activity was observed. The night's vagal activity suggested as one of the essential factor in development of hypertension remained unchanged in patients qualified into "dippers" hypertension group.

The role of vagal efferents in regulation of gastric emptying and motility in rats.

UNLABELLED: Nonpharmacologic regulation of gastrointestinal motility may become competitive to actually applied methods in the nearest future. The Aim of this study was to evaluate effect of vagal stimulation on gastric motility and emptying. Experiments were performed on 30 male Wistar rats in vivo. Electrodes (120 um O Cr/Mo Microfil Industries) were placed on right vagal trunk below diaphragm without affecting its integrity. The fistula was implanted in gastric antrum. Stimulation parameters were: 0.3 V; 0.5 Hz, impulse duration--10 msec, time stimulation--5 min. Gastric pressure (balloon, Synectics pressure transducer, Sweden) and gastric emptying (red phenol method) were measured subsequently during and between stimulations. RESULTS: Stimulation significantly decreased amplitude of gastric contractions about 14% (52.7 +/- +/- 24.5 vs control 66.8 +/- 15.0; p < 0.05) and increased liquid gastric emptying from isotonic solution about 10% (87.35 +/- 4.75 vs control 75.31 +/- 11.24; p < 0.001), hypertonic liquid about 15% (49.05 +/- 12.16 vs control 34.1 +/- 13.68; p < 0.001) and hypotonic liquid about 7% (83.05 +/- 8.8 vs control 76.29 +/- 11.88). The frequency of gastric contractions did not change significantly in Fast Fourier Analysis of the period of stimulations and in control group. CCK concentrations were not significantly different between stimulated and control group (0.3 +/- 0.08 vs control 0.27 +/- 0.06 pmol/L). L-NAME infusion abolished completely acceleration of gastric emptying of isotonic solution (50.38 +/- 12.66 vc control 87.82 +/- 5.49; p < 0.05), hypertonic solution (32.17 +/- 15.09 vs control 51.65 +/- 10.74; p < 0.05) and hypotonic solution (60.42 +/- 12.05 vs control 82.67 +/- 8.06; p < 0.05) during electrical stimulation. DISCUSSION: In this experiment efferent stimulation of abdominal vagal nerve release neuromediators from afferent and efferent fibers. The main regulator seems to be nitric oxide. These results indicate the effective vagal nerve stimulation affects gastric motility and emptying. It is likely that observed effects reflect integrated response with activating vago-vagal reflexes and neurohumoral factors.

[Disturbances of the autonomic nervous system in gastroesophageal reflux disease]. / Zaburzenia ukladu autonomicznego w chorobie refluksowej przelyku.

GERD (Gastroesophageal Reflux Disease) is a common clinical problem, which affects the upper part of the gastrointestinal tract. The pathophysiology of GERD is associated with dysfunction of the various mechanisms called "the anti-reflux barrier". Lately, the disturbances of the autonomic nervous system (ANS) have been stressed in the pathogenesis of the different diseases (including GERD). The HRV examination (Heart Rate Variability) seems to be the best non-invasive method to evaluate the disturbances of ANS. The aim of our study was to detect possible ANS disturbances in GERD patients. 23 persons (healthy volunteers and GERD patients) took part in the examinations. 24-h-esophageal pH-metry and the resting, "deep breathing" (DB) test, as a short-term measurement of heart rate variability, were performed in every person. The results proved that the GERD patients have abnormal low values of the basic components that make up the HRV spectrum (LF and HF obtained from rest record and HF from record during DB). We demonstrated the evidence of functional ANS disturbances, which may be responsible for the changing the HRV parameters of the frequency domain analysis in GERD patients. The disturbances mentioned above are supposed to influence the normal modulation of the X (vagus) nerve, which plays an important role in the maintaining the physiological LES function.

[Value of electrogastrographic parameters in evaluation of gastric myoelectrical activity]. / Wartosc parametrów elektrogastrograficznych w ocenie czynnosci mioelektrycznej zoladka.

Electrogastrography (EGG) is presently the only non-invasive method for the evaluation of gastric myoelectrical activity. In relation to the more and more described disturbances of the basic electrical rhythm in different pathological units EGG has been applied on a still larger scale. However, the data obtained from the EGG record do not reflect directly the gastric motility. This method allows only to make an indirect evaluation of the gastric motor disturbances. It still entails a great number of investigations so as to attain a better precisions of the evaluations of its clinical usefulness in gastroenterological diagnostics. This thesis presents the basic information on the methodology, the parameters under evaluation and the clinical application of the EGG method.

[Gastric motility disturbances in pancreatic cancer patients]. / Zaburzenia czynnosci motorycznej zoladka u pacjentów z rakiem trzustki.

Eighteen patients with confirmed pancreatic carcinoma without endoscopic evidence of mechanical gastroduodenal obstruction were included in the study. Aim was to determine changes in gastric myoelectric activity and liquid emptying (LGE) induced by pancreatic tumor growth. According TNM/UICC classification patients were divided in two groups A (T2) and B (T3) due to extend of expansion. Dyspeptic symptoms were observed in 4 patients of group A and 8 in group B. In group A dysrhythmic patterns of gastric myoelectric activity mostly bradygastria type were observed in 5 of patients and 8 in group B. LGE were delayed in 2 in group A and 5 in group B respectively. Disordered gastric myoelectric activity and emptying correlated with tumor stage and location. Delayed gastric emptying may be attributed to gastric dysrhythmia and abdominal pain that occur during the course of disease due to splamchnic plex infiltration.

[The effect of chronic alcohol use on heart rate variability]. / Wplyw przewleklego spozycia alkoholu na zmiennosc rytmu zatokowego serca.

A long lasting alcohol intake causes, amongst numerous systemic damages, also the autonomic nervous system (ANS) dysfunction, which causes the autonomic heart rate regulation disorders. The aim of the study was to evaluate the autonomic regulation of the circulation in chronic alcoholism. Seventeen alcoholics, 24-55 years of age (mean 43 +/- 5.2 years) were examined. They have been abstainers for 2-6 years. The cardiac ANS function was evaluated using the HRV measurement. The HRV was registered using V6 EKG lead. The recording was performed through the 15 min of resting conditions and 5 min of the deep breathing test. A group containing healthy volunteers, matched for age and gender, for the comparison of the HRV results was recruited. In the examined group, during the resting conditions, the significant RR period changes weren't observed (999.7 +/- 139.2 vs. 967 +/- 144.9; p > 0.05). The nonsignificant lower values of the spectral analysis parameters of HRV: LF (954.1 +/- 1162.6 vs. 1456.4 +/- 1327.1; p > 0.05) and HF (676.4 +/- 414.2 vs. 1557 +/- 1854.4; p > 0.05) and LF/HF ratio (1.5 +/- 1.14 vs. 1.38 +/- 1.28; p > 0.05) were also noticed. In response to the DB test, the mean value of the RR period wasn't significantly changed (921.4 +/- 152.3 vs. 930.6 +/- 137.8; p > 0.05). In DB test the significant decrease of LF (3465.8 +/- 2750.1 vs. 11558.6 +/- 7902.5; p < 0.001) and HF (406.1 +/- 366.8 vs. 1665 +/- 1757.1; p < 0.01) was observed. No significant change of LF/HF mean ratio (11.6 +/- 6.97 vs. 14.7 +/- 11.6; p > 0.05) was noticed. The results of our study indicate on the maintenance of the HRV disorders in chronic alcoholics, during the abstinence.

History traces of gastrointestinal motility in Poland.

The objectives of this chapter was to show how motility studies were developed and performed in Poland at the end of century to better understand pathophysiology and improve the clinicians ability to evaluate and treat patients with motility-related disorders. Some of the important historical points along the path to current understanding of the form and function of gastrointestinal motility are presented. Scarce information exists about other than Cracow and Wroclaw motility centers in Poland in previous century. Lately sophisticated technology became available in Poland and more centers have begun to yield more effective strategies of treatment and enhanced understanding of the pathophysiologic mechanisms underlying GI motility disorders.

Gastroduodenal alkaline response to acid and taurocholate in conscious dogs.

Alkaline secretion was measured in the fundic and antral portions of the stomach and in the upper and distal portions of the duodenum in conscious dogs under basal conditions, in response to luminal exposure of HCl and taurocholate, and after feeding. Topical application of HCl (6.7-100 mM) resulted in an increase in HCO-3 output, particularly from the upper duodenum, and this was associated with the rise in prostaglandin (PG) E2 release. Since both these effects were abolished by pretreatment with indomethacin, it was concluded that the stimulation of alkaline secretion by topical HCl is mediated by mucosal PGs. HCl instilled into the main stomach or feeding a meat meal also caused an increase in alkaline secretion from the isolated (non-acid-perfused) gastric and duodenal portions, but this effect was not affected by indomethacin, suggesting that it was not mediated by endogenous PGs. Direct exposure of the mucosa to luminal taurocholate (0.62-20 mM) adjusted to pH 6.0 also increased gastroduodenal HCO-3 output, but this effect was not affected by indomethacin and accompanied by a fall in transmucosal PD value, suggesting that it could be due to the damage of the mucosa and increased mucosal permeability to HCO-3. We conclude that gastroduodenal HCO-3 output increases in response to natural substances such as HCl, taurocholate, or feeding, and the mechanism of this increase differs depending on the stimulant used.

Gut hormones in stimulation of gastroduodenal alkaline secretion in conscious dogs.

Alkaline secretion from the fundic and antral pouches of the stomach and the loops of proximal and distal duodenum was measured in conscious dogs under basal conditions and after intragastric instillation of HCl solution, meat feeding, or intravenous infusion of various gut hormones. In control tests on fasted dogs HCO-3 output from the duodenal mucosa was severalfold higher than that from the gastric mucosa. Instillation of 10 mM HCl into the stomach resulted in a significant increment in HCO-3 secretion from the gastric pouches and proximal duodenal loops, and this was accompanied by a marked increase in plasma secretin, cholecystokinin (CCK), and pancreatic polypeptide (PP) levels. Meat feeding stimulated HCO-3 secretion from proximal duodenum, and it was accompanied by a significant elevation in plasma gastrin, secretin, CCK, gastric inhibitory peptide, and PP. Among exogenous hormones, the most effective stimulant of HCO-3 secretion was PP, which caused a significant increase in HCO-3 output from the gastric and duodenal mucosa at doses (125-500 pmol X kg-1 X h-1) that raised plasma PP to postprandial levels. CCK in physiological doses (21-85 pmol.kg-.h-1) also stimulated HCO-3 secretion from gastric pouches and proximal duodenal loops. Neurotensin stimulated HCO-3 secretion from both gastric pouches and duodenal loops. In contrast, gastrin or secretin did not affect significantly HCO-3 secretion from the gastroduodenal mucosa. This study provides evidence that some gut hormones, particularly PP, CCK, and neurotensin, may be involved in the physiological stimulation of gastroduodenal alkaline secretion.

Effect of stimulation of the vagus nerves and vagotomy on myoelectric activity of small bowel.

Experiments have been done on conscious dogs (6 animals) to study vagal influences on small bowel motility. First group (3 dogs) was prepared with gastric and esophageal fistulas, the second group (3 dogs) with gastric fistulas. Both groups had monopolar silver electrodes placed along small bowel. Stimulation of vagus with sham feeding (SF) increased MMC period of about 21%. Insulin and 2DG infused intravenously increased MMC period at lower dose range and in high doses induced fed-like pattern of motility. Supradiaphragmatic vagotomy done in the second group animals does not change significantly fasted as well as fed motility pattern. These data suggest that central and peripheral vagal input is required for inhibition MMC activity and development fed motility pattern.

Cholecystokinin in the regulation of intestinal motility and pancreatic secretion in dogs.

Peptidal (CR-1409) and nonpeptidal (L-364,718) cholecystokinin (CCK) receptor antagonists were used to determine the possible involvement of CCK in the fasted and fed intestinal motility patterns and the related alterations in pancreatic secretion. Dogs were implanted with electrodes along the small bowel and with chronic pancreatic fistulas. In fasted dogs, the typical migrating motor complex (MMC) cycles and accompanying fluctuations in pancreatic secretion were recorded. Neither of the CCK antagonists affected these motor and secretory components of the MMC. Feeding interrupted the MMC and increased spike activity at all levels of the small bowel, and this was accompanied by a significant increase in pancreatic secretion and in plasma hormone [gastrin, CCK, and pancreatic polypeptide (PP)] levels. Both CCK antagonists significantly reduced the postprandial spike activity but failed to restore the fasted pattern. Exogenous gastrin and CCK, as well as bombesin, induced fedlike motility patterns accompanied by marked pancreatic protein secretion. These effects were completely reversed to the fasted patterns during intravenous infusion of CCK antagonists. In contrast, cholinergic stimulation (bethanechol) induced a fedlike pattern that was more resistant to CCK antagonists. We conclude that CCK does not play a major role in the fasted motility pattern and related fluctuations in pancreatic secretion but may be partly involved (by itself and by released PP) in the induction of the fed motility pattern and the postprandial stimulation of the exocrine pancreas.

Relationships between duodenal motility and pancreatic secretion in fasted and fed dogs.

A relationship between duodenal myoelectric or motor activity and exocrine pancreatic secretion as well as plasma gut hormone levels has been investigated in fasted dogs, fed dogs, and dogs that were stimulated with exogenous gut hormones. Pancreatic secretion showed typical periodicity in phase with the myoelectric or motor activity of the duodenum. Fasting pancreatic bicarbonate and protein secretion reached peaks during phase III of the interdigestive migrating motor complex (MMC) cycle that were significantly larger than nadir levels occurring during phase I of the cycle. These fasting bicarbonate and protein peaks reached, respectively, approximately 9 and 30% of the highest postprandial outputs and 4 and 14% of the maximal secretory capacity elicited by secretin or CCK. They were accompanied by a significant rise in plasma motilin, gastrin, and pancreatic polypeptide (PP), but only exogenous motilin given in physiological dose induced motility pattern and pancreatic secretion similar to those observed during phase III. Feeding interrupted both motor and secretory MMC cycle, increased the pancreatic secretion to approximately 40-60% of the maximal secretory capacity, and was accompanied by increments in plasma gastrin, cholecystokinin (CCK), secretin, and PP. None of these hormones applied alone in physiological dose was capable of reproducing the postprandial inhibition of MMC cycles. We conclude that the pancreatic secretion in fasted dogs fluctuates periodically in phase with duodenal motility, but the phase III peak secretory outputs represent only minute fractions of the maximal secretory capacity and can therefore be ignored in regular testing of pancreatic secretion.