Effect of cisplatin on myoelectric activity of the stomach and small intestine in dogs

The effect of cisplatin on interdigestive myoelectric activity (IDMA) of the gastric antrum, duodenum and jejunum, plasma concentration of motilin, and animal behavior was studied in seven conscious dogs with gastric cannulas and platinum electrodes implanted on the serosal surface of antrum and upper small intestine. Cisplatin given intravenously in a dose of 2 mg/kg resulted in complete interruption of IDMA and produced predominantly phase II-like activity, lasting as long as 24 hr. Six of the seven dogs exhibited retropropagation of spike bursts from the jejunum to the antrum which was accompanied by emesis. Retropropagation of spike bursts did not occur in one dog who did not exhibit emesis. In addition, abnormal spike bursts occurred frequently, including simultaneously occurring spike bursts in both duodenum and jejunum and nonpropagating short spike bursts in isolated segments of the upper small intestine. As phase III of IDMA disappeared, plasma motilin concentrations remained comparable to those in phase II of normal IDMA but without the cyclic increases. These studies indicate that cisplatin interrupts the regular cycle of IDMA as well as the plasma motilin cycle and produces retropropagation of spike bursts and abnormal spike bursts. These changes in both motility and plasma motilin levels may play a part in the mechanism of emesis induced by cisplatin in dogs.This work was supported in part by The Genesee Hospital Gastrointestinal Research Fund and by U.S. Public Health Service Research Grants CA11198 and CA11083.     

Electrical activity of the stomach and upper intestine

Thecontrol andresponse electrical activities of the stomach and upper intestine have been described. Control activities are spontaneous, rhythmic activities which do not induce contractions directly but which do control contractions by controlling the appearance of response activities. Properties of the control activity (pacesetter potentials) of the stomach have been described and compared to the properties of the control activity of the upper duodenum. Differences between these control activities were stressed: only in the stomach can single pacesetter potentials be induced locally as desired (by intraarterial acetylcholine) and obliterated locally as desired (by intraarterial catecholamines). Using these procedures, it was shown that the pacesetter potential of the stomach is followed by a refractory period; can be abolished temporarily by collision with a premature potential which spreads in a retrograde direction, or by a local injection of catecholamines proximal to a recording site. These findings and other evidence suggest that the pacesetter potentials of the stomach may differ from those of the intestine, and present a challenge to current models (eg, coupled relaxation oscillators) for the control activities of the gastrointestinal tract. The electrical activity of the stomach can be manipulated experimentally, and this would be advantageous in testing the applicability of models to gastrointestinal electrical activity.Supported by a grant from the Life Insurance Medical Research Fund.     

A-V conduction in hyper- and hypothyroid dogs

Dogs were made hyper- or hypothyroid by daily feeding of thyroid powder or intraperitoneal injection of ¹³¹I, and serum thyroxine levels were determined to confirm their abnormal thyroid states. Conduction time (CT) and functional refractory period (FRP) of the A-V conduction system were studied in these dogs for comparison with those of control dogs. In the hyperthyroid group, A-V CT and FRP were markedly shortened, and the frequency at which the A-V conduction system can transmit rapid atrial impulses was significantly increased. The opposite changes were observed in the hypothyroid group. A-V CT and FRP decreased in the control and hyperthyroid groups during infusion of epinephrine at a rate of 1 mcg. per kilogram per minute, and these changes were comparable in both groups in terms of per cent changes. The results indicate that thyroid hormone markedly facilitates the impulse transmission through the A-V conduction system, and the action appears to be direct and independent of the sympathetic activity. This action may explain extremely rapid ventricular responses and increased digitalis requirements seen in thyrotoxic patients with atrial fibrillation.     

Myoelectrical activity and intraluminal flow in human sigmoid colon

Myoelectric spike bursts were recorded in the sigmoid colon by means of an intraluminal silastic tube equipped with 3 Ag–AgCl ring electrodes fixed 15 cm apart on the tube that was introduced by flexible sigmoidoscopy. In six subjects, the tube was also equipped with three catheters whose tip opened 1 cm aborad from each electrode, for pressure recordings. In six other subjects, the tube was equipped with both electrodes and a catheter opening at the tip of the probe for infusing fluids at a rate of 12 ml/min into the colonic lumen. The fluid was collected with another tube inserted in the rectum and the volume was measured at 1-min intervals. Colonic spiking activity was made of rhythmic stationary bursts (RSB) and of sporadic bursts that were either propagating (SPB) or not propagating (SNPB). All sporadic bursts were associated with intraluminal pressure waves whose amplitude was significantly higher than that associated with rhythmic bursts. In the infusion experiments, the volume of fluid collected did not change significantly whether rhythmic bursts were present or not (3.9±1.7 ml/min and 3.3±1.9 ml/min respectively) (mean±sd). However, the volume was significantly higher when sporadic nonpropagating bursts were present (9.4±4.1 ml/min), and even higher when the sporadic bursts were propagating (21.6±8.8 ml/min). These results indicate that (1) the occurrence of sporadic bursts, particularly when propagating, is associated with intraluminal pressure waves that lead to significant propulsive movements; and (2) rhythmic bursts do not seem to be involved in colonic propulsive activity.This work was supported by the grant DG282 from the Medical Research Council of Canada.     

Computer aided analysis of electrical and mechanical activity of stomach and duodenum

In studies of gastroduodenal motility several imaging techniques and also recordings of signals of implanted transducers are used. Combination of methods and prolonged observation times produce so much information that an automatic analysis is advantageous, the more so because more complex parameters can be analysed. Using a desktop computer, it is possible to analyse long time-series of antral and duodenal signals, obtained with implanted electrodes and strain gauges. The developed program can discriminate between the signal and the majority of artefacts. An easy manual interaction on the computer display enables the operator to either accept or adjust the indicators of recognized signals. The times of occurrence and the amplitudes of the detected peaks are retained for further analysis e.g. production of histograms of interval time, amplitude, antroduodenal time lag, or calculation of coordination parameters.     

Myoelectrical activity of the Billroth II gastric remnant.

This study was undertaken to investigate the extent to which gastric electrical control activity and phasic contractile activity are preserved after Billroth II resection and to assess the relation between these activities and postprandial symptoms in patients who have undergone Billroth II resection. Thirty three patients were studied after Billroth II resection without vagotomy. Gastric electrical activity was recorded from surface electrodes and intraluminal pressure was recorded simultaneously. The electrogastrographic signals were analysed by Running Spectrum Analysis. In addition, three dogs with a Billroth II stomach and implanted serosal electrodes were studied. Phasic gastric pressure waves were observed in most patients. Electrogastrographic signals recorded from 82% of the Billroth II patients contained a mean (SD) peak at 3.1 (0.2) cycles per minute (cpm). Fasting and postprandial frequencies correlated significantly (p less than 0.02) with the score for nausea and vomiting. In 61% of the patients, the electrogastrographic signal contained a stable component with a frequency of 10.5 (0.6) cpm that was not caused by respiration. We suggest that this activity is of intestinal origin. In all three dogs studied, retrograde conduction of jejunal electrical control activity (16 cpm) into the distal part of the gastric remnant was observed. In the Billroth II patients, the presence of a 10 cpm component correlated negatively with symptoms.     

Inhibition of gastric acid secretion normalizes interdigestive motor activity in the stomach in dogs

Recently, intragastroduodenal acidity has been shown to play an important role in interdigestive gastrointestinal motility. In this study, gastrointestinal motility and intragastric pH changes were monitored simultaneously in dogs, to characterize 1) the relationship between intragastric pH changes and IMC, and 2) the effects of intragastric acidity on motilin-induced phase III contractions in the gastric antrum by using secretagogues and an H2 receptor antagonist (cimetidine). As a result, intragastric pH showed periodic changes with gastric IMC in conscious dogs. Furthermore, motilin-induced gastric phase III contractions were inhibited by gastric acidification. But inhibition of gastric acid secretion by cimetidine normalized both the motor index and migration of the contractions. In conclusion, gastric acid secretion may influence the sensitivity to motilin of the stomach, and play an important role in the regulation of interdigestive gastric motility.     

Small intestine pouches as a therapeutic principle in stomach and large intestine replacement

Small bowel pouches are being utilized in several versions as substitute reservoirs after total gastrectomy and after continence preserving proctocolectomy. Throughout the world, most frequently the pouch is formed by simple duplication of the gut. The principles of reservoir formation, the special functional requirement in the upper and lower GI-tract are delineated. Follow-up studies prove the successful use of gastric and ileoanal pouches.     

Ghrelin-producing endocrine tumors of the stomach and intestine

Ghrelin is a novel gastrointestinal hormone produced by about 20% of the rat and human gastric neuroendocrine cell population, which possesses strong GH-releasing activity, but also plays other central and peripheral roles, including influence on food intake, gastric motility, and acid secretion. The aim of the present study was to determine whether gastrointestinal endocrine hyperplastic and neoplastic lesions produce ghrelin, at both protein (immunohistochemistry) and mRNA (in situ hybridization and/or RT-PCR) levels, and express the GH secretagogue receptor mRNA by RT-PCR. Sixteen gastric and 20 intestinal carcinoids as well as normal gastrointestinal mucosa and atrophic gastritis-associated neuroendocrine cell hyperplasia were studied. The majority (12 of 16, 75%) of gastric carcinoids and only 5 of 18 (27%) of intestinal endocrine tumors were immunoreactive for ghrelin. In situ hybridization confirmed the immunohistochemical data, but also showed ghrelin mRNA in 1 gastric and 8 intestinal additional tumors. RT-PCR showed ghrelin mRNA in 14 of 14 cases, indicating a low level of ghrelin gene expression in all gastrointestinal endocrine tumors tested. Gastric neuroendocrine hyperplastic cells were also strongly positive for ghrelin. GH secretagogue receptor mRNA was absent in 3 gastric, but present in 7 of 11 intestinal carcinoids studied by RT-PCR. These findings demonstrate that most gastric carcinoids (and related neuroendocrine cell hyperplasias) and some intestinal carcinoids produce ghrelin. These hyperplastic/neoplastic conditions could represent the clinical model to clarify the existence and impact of ghrelin hypersecretion on endocrine and nonendocrine functions.     

Inhibition of interdigestive contractile activity in the stomach by peptide YY in Heidenhain pouch dogs

The inhibitory effect of peptide YY on contractile activity in the innervated main stomach and the vagally denervated fundic pouch in conscious Heidenhain pouch dogs was investigated. Peptide YY was given in i.v. bolus injections of doses between 12.5 and 100 pmol/kg body wt. During the digestive state, 2-3 h after feeding, peptide YY was found to have no effect on contractile activity in either the innervated or the vagally denervated stomach. In the interdigestive state, it was found that peptide YY inhibited the interdigestive migrating contractions in the innervated main stomach dose-dependently for 1.2 +/- 0.1 to 5.8 +/- 0.3 min, but did not affect pouch contractions at all. This peptide, however, did not influence the cycle of the interdigestive migrating contractions. Pentagastrin, on the other hand, suppressed the interdigestive migrating contractions in the innervated main stomach when the bolus doses were greater than 300 pmol/kg body wt, but did not inhibit pouch contractions completely with this dose. Atropine (0.05 mg/kg body wt) suppressed contractions in both the main stomach and the vagally denervated pouch. Peptide YY inhibits the interdigestive migrating contractions in the stomach through the extrinsic nerves.     

Nitric oxide synthase activity in hyperthyroid and hypothyroid rats

OBJECTIVE: Thyroid disorders are accompanied by important changes in haemodynamic and cardiac functions and renal sodium handling. Since nitric oxide (NO) plays a crucial role in regulating vascular tone and renal sodium excretion, the present paper was designed to determine whether changes in the activity of NO synthase (NOS) participate in the cardiovascular and renal manifestations of thyroid disorders. METHODS: We measured NOS activity in the heart (left and right ventricles), vessels (aorta and cava) and kidney (cortex and medulla) of euthyroid, hyperthyroid and hypothyroid rats after 6 weeks of treatment. NOS activity was determined by measuring the conversion of L-[(3)H]-arginine to L-[(3)H]-citruline. RESULTS: NOS activity was higher in all tissues from hyperthyroid rats when compared with controls, except in the right ventricle. In the hypothyroid group, NOS activity showed a more heterogeneous pattern, with significant increases in both ventricles but significant reduction in the aorta, while in the vena cava, renal cortex and medulla the enzyme activity also tended to be higher, but significance was not reached. CONCLUSIONS: These data indicated that NOS activity was upregulated in tissues primarily related to blood pressure control in hyperthyroid rats, suggesting that an increased NO production may contribute to the hyperdynamic circulation in hyperthyroidism and may have a protective homeostatic effect in the target organs of the hypertension that accompanies this endocrine disease. The aortic and renal findings in hypothyroid rats suggested a possible role for NOS in the increased peripheral resistance and the normal pressure-diuresis-natriuresis response of these hypotensive animals, although hypothyroidism produced a heterogeneous tissue response in NOS activity.     

Electrodermal activity in hypothyroid patients and healthy subjects.

The involvement of the central nervous system either in hypothyroidism or in hyperthyroidim has previously been shown on the basis of visual, auditory, somatosensory, and central motor evoked potential studies by some investigators. In to our previous study, we found that abnormal electrodermal activity in nonmedicated hyperthyroid patients was not associated with psychiatric symptoms. In this study, our purpose was to investigate whether hypothyroidism results in electrodermal abnormalities in the absence of measurable psychiatric symptoms. Electrodermal activity was recorded with a skin conductance unit connected to a personal computer. Basal levels of electrodermal activity and responsiveness to repeated acoustic stimulation were studied in 14 nonmedicated hypothyroid patients and 14 healthy controls. Psychiatric rating scores indicated that patients and healthy controls had normal levels of anxiety and depression. Hypothyroid patients had lower skin conductance levels, lower fluctation rates and prolonged onset latencies compared with controls. None of the hypothyroid patients had amplitude changes. In conclusion, hypothyroid patients may have abnormal electrodermal activity that is related to the change of hypothalamic-pituitary-thyroid axis function, without associated psychiatric symptoms.     

Early clinical diagnosis of stomach and large intestine cancer

Gastric and colonic cancer, which affect alarmingly also younger age groups to a growing extent, are developing into a serious problem of public health. Not recognized in time, the survival probability is low. The 5-year survival time is 10% with a manifest gastric carcinoma, with colonic cancer it is 30%. If these neoplasias are recognized in a stage in which they correspond to the criteria of an early carcinoma, the chance of recovery will be 90% for the patients. The early gastric carcinoma does not occur without any symptoms, but in more than 80% of the cases it causes differently intensely pronounced symptoms in the epigastric region, with pain, dyspepsia, haemorrhage and loss of weight prevailing. Therefore, epigastric, complaint for more than 4 weeks should give reason for a thorough gastroenterological examination, with endoscopy being superior to radiological examination, even when using advanced methods of examination. Special control is needed for patients of the various risk groups. Patients with a morbus Ménétrie, a pernicious anaemia and a chronic-atrophic gastritis with intestinal metaplasia of the colonic type are exposed to a particularly high risk of carcinoma. Of a special practical importance is the circumstance that a peptic ulcus of the stomach may develop in an already carcinomatously changed mucosa and thus the carcinoma continues growing below a healed peptic lesion. Thus, a gastric ulcer requires a regular and short-term endoscopic control until its final macroscopic and histological healing. The malignant diseases of stomach and large intestine show an inverse behaviour over the past 20 years. The colonic carcinoma develops from an adenoma in 90% of the cases. In most of the cases, this development from the precursors is without any symptoms. Symptoms such as blood in the stools, abdominal pain, change in the action of the bowels, loss of weight, decrease in power and the like indicate already an advanced carcinoma. Among the laboratory tests, only the examination of the faeces for concealed haemorrhage is of some importance as a diagnostic test. The CEA test in not suitable therefore. As also larger adenomas bleed intermittently, there is the chance of recognizing also these prestages of carcinomas by regular examinations of the faeces. In contrast to the simple barium enema, the radiological examination in double contrast reveals changes of the mucosa of the colon up to a size of 1 cm in more than 80% of the cases. Coloscopy, however, is superior to X-ray examination, regarding both expressiveness and efficiency.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of hypoxia on the mechanical activity of the canine small intestine

Summary The effects of 4 hr. of hypoxia on the contractile activity of intact jejunal segments of unanesthetized animals was investigated by use of extraluminal force transducers. The frequency of contraction of the longitudinal and transverse axes was less than that in normal segments. Although spikes initiate contraction, the slow-wave frequency determines the maximal contractile frequency of both muscle layers. The myenteric plexus synchronizes the contractile patterns between muscle layers and coordinates contractile activity between adjacent intestinal segments. The plexus appears to regulate the level of intestinal tone.Taken in part from a thesis submitted by Joseph Szurszewski in partial fulfillment of the requirements for the Ph.D. degree, University of Illinois, Urbana, Ill., and published in part as a preliminary report inPhysiologist 9:301, 1966.Supported by Crant I-FI-GM-29-523 from the National Institutes of Health, U. S. Public Health Service.The authors wish to thank Dr. Paul Bass, Parke, Davis & Company, for the use of his facilities in order to learn the method for constructing the force transducers. The senior author is indebted to Professor C. Ladd Prosser for his suggestions and to the Department of Physiology and Biophysics, University of Illinois, for the use of its facilities.     

Effects of hypoxemia on coronary blood flow and cardiac output in normal and hypothyroid dogs

Simultaneous determinations of coronary blood flow by the nitrous oxide desaturation method and of cardiac output by the direct Fick arteriovenous oxygen difference method were made on dogs breathing 100%, 10% and 5% oxygen-nitrogen mixtures under morphine chloralose anesthesia. The observations were repeated with 100% oxygen and 10% oxygen- 90% nitrogen mixtures after a hypothyroid state had been induced by administration of 35 mc. of I¹³¹. Parallel increases in coronary blood flow and cardiac index occurred in the normal dog with progressive hypoxcmia. In the hypothyroid dog the cardiac index did not change significantly, and the increase in coronary blood flow was only about 50 per cent of the value observed in the normal group. The failure of the hypothyroid dog to demonstrate an increased cardiac index in response to hypoxemia is attributed to the removal of the potentiating action of the thyroid hormones upon the catecholamines of the sympathoadrenal system. The reduced but still significant increase in coronary blood flow in the hypothyroid group is brought about by hypoxic stimuli that act independently of hormonal influences.