Supersensitivity and gastric emptying after vagotomy

Investigations were carried out in man and dog to study the validity of Cannon's law of denervation supersensitivity in relation to parasympathetic denervation of the stomach. Subthreshold doses of carbachol did not accelerate gastric emptying before vagotomy but caused a significant increase in the rate of gastric emptying after vagotomy. These findings may be relevant to aberrations of gastrointestinal motility after vagotomy and may provide the basis of a test for completeness of gastric vagotomy.     

Gastric emptying following vagotomy and antrectomy and proximal gastric vagotomy.

Gastric emptying of solid meals labelled with 129Cs was studied in patients for up to one year after vagotomy and antrectomy or after proximal gastric vagotomy. Significant delay was found one month after vagotomy and antrectomy but this had returned to normal by six months. No delay was found after proximal gastric vagotomy. The effect of posture on gastric emptying was also studied in the same subjects. No significant differences were found between gastric emptying in the supine or sitting positions after solid meals.     

Progression of changes in gastric emptying of hypertonic liquids after proximal gastric vagotomy

Gastric emptying rates of hypertonic (10%) dextrose liquid meals were studied in five dogs before, and 3, 6, and 12 months after proximal gastric vagotomy (PGV) without drainage. The purpose of this study was to determine if operation-related changes in emptying rates normalized or became more disparate during the year after PGV. An increased rate of emptying during the first 5 min after ingestion was seen at 3 months after PGV, which significantly increased (P<0.025) after 6 and 12 months. The remainder of the meal after PGV emptied at a regulated exponential rate unchanged throughout the postoperative year from its preoperative rate. Total volumes of gastric aspirate at four intervals after meal ingestion did not significantly change across the four test periods in respect to endogenous secretion or pH acidity.Supported by The Veterans Administration.     

Effect of calcitonin on gastric emptying

The effect on gastric emptying of synthetic salmon calcitonin administered intravenously (415 pmol bolus injection followed by infusion to reach an overall dose of 62.25 pmol.kg-1 body mass) versus placebo was examined in 13 healthy men. Gastric emptying of a radiolabeled solid meal was assessed with a gamma camera. The gastric emptying course was analyzed with the use of the power-exponential fitting. A marked delay in gastric emptying was observed in all subjects studied: the median gastric half emptying time was 60.3 min after placebo and 196.5 min after calcitonin (p less than 0.001). At the same time, analysis of the parameter S revealed that calcitonin did not elicit any consistent change in the shape of gastric emptying curves.     

Effect of erythromycin on gastric emptying

INTRODUCTIONMotility is a general term that embraces allmovements of the gastrointestinal tract,such as con-tractions of smooth muscle,the intralumunal pres-sures,and the transit of chyme throughout thebowel.These movements are modified by the actionsof specialized segments of the intestine and thesphincters,and the whole is integrated by neural andhumoral levels of control.Motility is best understoodteleologically,i.e.as a process that facilitates theother,more fundamental functions of the gut.Thestomach has three major functions:     

Erythromycin enhances gastric emptying in patients with gastroparesis after vagotomy and antrectomy

We studied the effect of erythromycin on gastric emptying in nine patients with gastroparesis following truncal vagotomy and antrectomy, and assessed their clinical response to chronic oral erythromycin. Gastric emptying was evaluated using a solid-phase radio-labeled meal. Patients were studied after erythromycin 200 mg intravenously (N=9) and after an oral suspension of erythromycin 200 mg (N=7) each given 15 min after ingestion of the meal. Three parameters of gastric emptying were analyzed: half-emptying time (T1/2), area under the curve, and percent gastric residual at 2 hr. Nine patients were subsequently placed on oral suspension erythromycin 150 mg three times a day before meals (range 125–250 mg three times a day) and symptoms of nausea, vomiting, postprandial fullness, and abdominal pain were assessed before and after erythromycin. Intravenous erythromycin markedly accelerated the gastric emptying (all three parameters studied) of solids (P<0.01) in seven of nine patients with postsurgical gastroparesis [baselineT1/2 154±15 min; after intravenous erythromycin,T1/2 56±17 min (mean ±sem)]. Oral erythromycin enhanced (P<0.05) the gastric emptying rate (T1/2, area under the curve) in five of seven patients (baselineT1/2 146±16 min; after oral erythromycin,T1/2 87±20 min). Of the nine patients who were placed on oral maintenance erythromycin, three showed clinical improvement after two weeks. In summary, erythromycin significantly enhances gastric emptying in many patients with vagotomy and antrectomy-induced gastroparesis; however, only a small subset of patients respond clinically to chronic oral erythromycin.Dr. Belinda Ramirez is in private practice in San Antonio, Texas.     

Effect of the menstrual cycle on gastric emptying

Gastric emptying of both solid- and liquid-phase markers was assessed in 7 normally-menstruating women who had undergone bilateral Fallopian tube ligations. The women were studied once during the follicular phase of their menstrual cycle and again during the luteal phase. Emptying of the liquid-phase marker was not significantly different during the two phases of the menstrual cycle. However, emptying of the solid-phase marker was significantly slower during the luteal phase of the cycle as compared to the follicular phase. This impairment of gastric emptying of solid was correlated with elevated serum levels of progesterone. This study demonstrates that the rate of gastric emptying of solids may vary with the phases of the menstrual cycle.     

Effect of altered gastric emptying on caffeine absorption

The effect of altered gastric emptying on caffeine absorption (tablets; 366.1 mg) was studied in patients with gastric stasis or after Billroth II partial gastrectomy with adequate gastric emptying and in healthy subjects with slowed gastric emptying due to a fibre-free and a fibre-rich liquid test meal of an elemental diet, respectively. Compared with controls (n = 15), a significantly slowed caffeine absorption was found in gastric stasis (n = 8) by means of a lower absorption rate constant KA (0.018 +/- 0.007 vs. 0.122 +/- 0.110 min-1 in controls) and a prolonged peak time tmax (160 +/- 77 vs. 46 +/- 19 min). Similar results were obtained after a fibre-free and a fibre-rich liquid test meal, respectively (n = 8 and n = 8, respectively; KA 0.035 +/- 0.01 and 0.035 +/- 0.023 min-1, respectively; tmax 91 +/- 24 and 93 +/- 23 min, respectively vs. KA 0.10 +/- 0.06 min-1 and tmax 50 +/- 14 min in controls; n = 7). After B II with adequate gastric emptying (n = 11) the absorption rate was within the normal range. The significantly lower average of the peak concentration cmax and of the area under the serum concentration-time curve x elimination rate constant (AUC x KE) in gastric stasis (5.9 +/- 1.8 micrograms/ml and 8.9 +/- 3.2 mg/l, respectively) and after B II partial gastrectomy (8.8 +/- 2.6 micrograms/ml and 10.8 +/- 3.0 mg/l, respectively) compared with controls (17.7 +/- 9.4 micrograms/ml and 20.8 +/- 10.7 mg/l respectively) probably reflect reduced bioavailability, which is apparently unchanged after a liquid test meal.     

Relationship between gastric emptying of a solid meal and emptying of the gall bladder before and after vagotomy.

Little is known of the temporal and quantitative relationships between emptying of the stomach and of the gall bladder in patients with duodenal ulcer before and after vagotomy. A non-invasive double isotope technique was used to investigate these relationships in 27 patients with a duodenal ulcer, before and after operation-truncal vagotomy and pyloroplasty (TV + P; n = 15) and highly selective vagotomy (HSV; n = 12). A further 25 patients were studied after operation (TV + P, n = 20: HSV, n = 5). 99Tcm-EHIDA was used as the biliary tracer and 113Inm bran as the gastric content tracer. In patients with a duodenal ulcer before surgery and in 16 of the 17 patients studied after HSV, the patterns of gall bladder emptying were similar to those previously found in normal subjects. In 60% of patients after TV + P, patterns of gall bladder emptying were altered and the onset of gall bladder emptying was significantly delayed (p less than 0.001) compared with unoperated patients and patients with a HSV. The rate of gall bladder emptying did not correlate with the rate of gastric emptying in any of the patients studied. These observations suggest that TV + P, but not HSV, causes considerable alteration in coordination of gall bladder and gastric emptying.     

Effect of proximal gastric vagotomy on gastric acid secretion and plasma gastrin

Sixteen patients underwent proximal gastric vagotomy (highly selective vagotomy) for chronic duodenal ulceration. All were subjected to preoperative and postoperative acid secretion studies. A reduction in the secretory response to pentagastrin and abolition of the response to meat extract occurred postoperatively.Plasma gastrin levels in response to meat extract were studied by radioimmunoassay. Basal plasma gastrin levels were unaffected by vagotomy and it was found that the plasma gastrin response to meat extract was not impaired after operation if the postoperative insulin test was positive. Only if the insulin test was negative was the amount of gastrin released by meat extract reduced.     

Mechanisms governing the biphasic pattern of gastric emptying after truncal vagotomy and pyloroplasty.

The pattern of gastric emptying after truncal vagotomy and drainage is usually biphasic. An early rapid phase is followed by a characteristically abrupt transition to slow emptying. The mechanisms responsible for this pattern were studied in six dogs with truncal vagotomy and pyloroplasty, fitted with a proximal duodenal cannula. Gastric emptying was measured using gamma camera imaging of a radiolabelled 15% dextrose test meal. Sixty one hour studies were done using five designs. (1) With the cannula closed gastric emptying was initially rapid, followed by stasis (emptying at 15 min - 32% (5.3), 60 min - 34% (4.8); mean (SE)). (2) With the cannula open emptying was very rapid (15 min - 76% (4.2) p less than 0.001, 60 min - 88% (2.6) p less than 0.001 ANOVA). (3) Distal duodenal instillation of isotonic saline, at a rate equivalent to gastric emptying with the cannula closed, did not retard this rapid emptying (15 min - 78% (10.6), 60 min - 90% (5.4)). (4) With duodenal instillation of 15% dextrose, gastric emptying remained faster than in studies without diversion (15 min - 50% (7.0) NS, 60 min - 65% (6.8) p less than 0.01), but was slower than during diversion alone (p less than 0.05). (5) Finally, duodenal instillation of 15% dextrose before administration of the test meal produced slower initial emptying without subsequent stasis (15 min - 24% (4.5), 60 min - 47% (10.6)), although the amounts emptied were not significantly different from those with the cannula closed. These results indicate that after truncal vagotomy and pyloroplasty small bowel resistances play a significant role in controlling gastric emptying. Osmoreceptor responses persist after truncal vagotomy, but sympathetic inhibitory responses to small bowel distension are not involved in the regulatory process.     

Gastric emptying after vagotomy and pyloroplasty

Emptying of liquids from the stomach was studied in 19 patients who had had a vagotomy and pyloroplasty and the results compared with 12 patients with duodenal ulcers and 9 patients with normal upper gastrointestinal tracts. The patterns of gastric emptying after vagotomy and pyloroplasty was found to consist of a very rapid initial emptying phase followed by emptying at a rate rather faster than in the other two groups. There was no difference in the gastric emptying of patients with duodenal ulcer and those with a normal gastrointestinal tract. Patients who complained of postprandial fullness and dumping after vagotomy and pyloroplasty had extremely rapid initial gastric emptying, more than half the test solution leaving the stomach almost immediately. Three patients who had postoperative gastric ulcers, 2 patients with vomiting since operation and 1 with postvagotomy persistent diarrhea showed a starting index and half-life similar to those of asymptomatic postoperative patients and only minor differences in the emptying time.Serial tests at varying intervals during the weeks after operation showed the gastric emptying of liquids was faster than normal from the earliest postoperative test. Over the succeeding weeks, emptying became still faster and probably reached a static state in 2 or 3 months.Supported by the South African Council for Scientific and Industrial Research and the Medical Research Council of South Africa, the Ben May Gastroenterology Research Fund and the Herman Staff Research Fund.The authors would like to thank Dr. J. G. Burger, Medical Superintendent, for permission to publish.     

Effect of sildenafil on gastric emptying in healthy adults

Background and Aim: Phosphodiesterase type 5 hydrolyzes and inactivates cyclic guanosine monophosphate produced by the nitric oxide‐stimulated guanylate cyclase. Sildenafil is a potent, reversible, and highly selective inhibitor of this phosphodiesterase. It causes smooth muscle relaxation by increasing intracellular concentrations of cyclic guanosine monophosphate. The aim of this study was to test the hypothesis that sildenafil alters gastric emptying and the intragastric distribution of food in healthy adults. Methods: Nine normal subjects (mean age 28 years, range 25–33) were given a placebo or a tablet of sildenafil (50 mg) at different times along with radio‐opaque markers. A gastric emptying scan was used to calculate the t_1/2 for gastric emptying (the time taken for the initial radioactivity to fall by 50%). Intragastric food distribution was also assessed using the gastric emptying scan to calculate proximal gastric emptying t_1/2, the proximal volume (the highest activity value in the proximal stomach at any time point in the study), and the distal volume (the highest activity value in the distal stomach at any time point in the study. Gastric emptying of an indigestible solid meal was assessed by calculating gastric clearance of radio‐opaque markers. Results: Sildenafil did not change total gastric emptying or gastric clearance of radio‐opaque markers. It shortened the proximal T_1/2, decreased proximal volume, and significantly increased distal volume. Conclusion: Sildenafil alters the intragastric distribution of food rather than causing gastric stasis.     

Effect of nifedipine on gastric emptying in normal subjects

We studied the effects of the calcium-channel blocker, nifedipine, on solid and liquid phases of gastric emptying in 10 healthy male volunteers. Each subject underwent a dual-isotope radionuclide gastric emptying determination with and without the preadministration of nifedipine, 30 mg orally, given 20 min prior to ingestion of the test meal over 10 min, following which the subject lay supine under the gamma-counter for 2 hr. Blood samples for measurement of plasma nifedipine concentration were obtained at the time of drug administration and every 30 min throughout the gastric emptying determination. There was a threefold variation in the areas under the plasma nifedipine concentration vs time curve (AUC) obtained in these 10 subjects. Percent gastric retention of either the liquid (water) or the solid (chicken liver) marker was not significantly different after 30 mg oral nifedipine, as compared to the nontreatment day. We concluded that plasma nifedipine concentrations previously reported to be associated with significant esophageal motility effects in humans were not associated with effects on gastric emptying of either liquids or solids.