Effects of morphine on colonic myoelectric and motor activity in subhuman primates

1990 ◽  
Vol 258 (2) ◽  
pp. G247-G252 ◽  
Author(s):  
C. T. Frantzides ◽  
R. E. Condon ◽  
W. J. Schulte ◽  
V. Cowles

We investigated the effects of numerous doses of morphine on colonic myoelectric and motor activity in monkeys. In each of four monkeys (Macaca arctoides), combined strain gauge transducers and bipolar electrodes were chronically implanted at four defined sites in the colon and recordings were made for 3 h in fasted, unanesthetized animals before and after intravenous administration of morphine sulfate (10-1,000 micrograms/kg). The basal fasting pattern of colonic motility was characterized by random contractions, nonmigrating clusters of contractions, and migrating individual contractions. Morphine at very low doses (10-25 micrograms/kg) had no effect on colonic motility at any site. At doses of 50-200 micrograms/kg, clusters and migrating contractions were eliminated, but there was an overall increase in the frequency of random contractions without an alteration in contraction amplitude or duration. At morphine doses of 500 and 1,000 micrograms/kg, contraction clusters and migrating contractions also were not seen, but there was a decrease in the colonic motility index caused entirely by a decreased frequency of random contractions. Both stimulation and inhibition were most marked in the sigmoid colon. Morphine has a dose-dependent biphasic effect on colonic myoelectric and contractile activity and alters colonic motility patterns by inhibiting migrating contractions and clusters of contractions.

1983 ◽  
Vol 245 (4) ◽  
pp. G582-G588 ◽  
Author(s):  
W. J. Snape ◽  
S. Shiff

Colonic motility was examined in the proximal (taeniated) and distal (nontaeniated) colon of New Zealand White rabbits. Colonic myoelectric and contractile activities were recorded by bipolar electrodes and extraluminal strain gauges sewn on the antimesenteric serosal surface of the proximal and distal colon. Slow-wave frequency consistently was slower in the proximal colon (13.2 +/- 0.9) compared with the distal colon (15.8 +/- 1.2) (P less than 0.05). During the control period 81.8 +/- 5.2% of slow waves have superimposed spike potentials in the proximal colon. The distal colon had similar amounts of spike activity. The distal colon had increased base-line contractility (P less than 0.02). Atropine inhibited spike and contractile activity on both sides of the colon, but the distal colon still had more contractile activity than the proximal colon (P less than 0.02). The alpha-adrenergic agonist phenylephrine and antagonist phentolamine had no effect on colonic motility. Isoproterenol inhibited colonic smooth muscle spike and contractile activity. This effect was blocked by propranolol. Administration of trimethaphan camsylate caused an increase in spike and contractile activity only in the distal colon. The effect of trimethaphan on the distal colon was inhibited by atropine. These studies show that 1) tonic cholinergic stimulation exists both in the proximal and in the distal colon, 2) circulating catecholamines have minimal effect on base-line colonic motility, and 3) tonic nonadrenergic inhibition of the distal colon modulates the tonic cholinergic stimulation.


2006 ◽  
Vol 290 (6) ◽  
pp. R1537-R1541 ◽  
Author(s):  
Kiyoshi Tsukamoto ◽  
Yukiomi Nakade ◽  
Christopher Mantyh ◽  
Kirk Ludwig ◽  
Theodore N. Pappas ◽  
...  

Corticotropin releasing factor (CRF) is one of the most important factors in the mechanism of stress-induced stimulation of colonic motility. However, it is controversial whether stress-induced stimulation of colonic motility is mediated via central or peripheral CRF receptors. We investigated the hypothesis that peripherally injected CRF accelerates colonic motility through the central CRF receptor, but not the peripheral CRF receptor. A strain gauge transducer was sutured on the serosal surface of the proximal colon. Colonic motility was monitored before and after the peripheral injection of CRF. An in vitro muscle strip study was also performed to investigate the peripheral effects of CRF. Subcutaneous injection of CRF (30–100 μg/kg) stimulated colonic motility in a dose-dependent manner. The stimulatory effect of peripherally administered CRF on colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and intracisternal injection of astressin (a CRF receptor antagonist). No responses to CRF (10−9 −10−7 M) of the muscle strips of the proximal colon were observed. These results suggest that the stimulatory effect of colonic motility in response to peripheral administration of CRF is mediated by the vagus nerve, nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem. It is concluded that peripherally administered CRF reaches the area postrema and activates the dorsal nucleus of vagi via central CRF receptors, resulting in stimulation of the vagal efferent and cholinergic transmission of the proximal colon.


2000 ◽  
Vol 279 (2) ◽  
pp. G311-G318 ◽  
Author(s):  
Julia K. L. Walker ◽  
Raul R. Gainetdinov ◽  
Allen W. Mangel ◽  
Marc G. Caron ◽  
Michael A. Shetzline

The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic smooth muscle segments from wild-type and DA transporter knockout (DAT −/−) mice. In wild-type mice, combined blockade of D1 and D2 receptors resulted in significant increases in tone (62 ± 9%), amplitude of spontaneous phasic contractions (167 ± 24%), and electric field stimulation (EFS)-induced (40 ± 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT −/− mice relative to wild-type mice. These differences were eliminated by combined D1 and D2 receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT −/− mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT −/− mice relative to wild-type mice. The fact that spontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon.


1989 ◽  
Vol 257 (4) ◽  
pp. G601-G606 ◽  
Author(s):  
E. E. Soffer ◽  
P. Scalabrini ◽  
D. L. Wingate

The study of human colonic motility under physiological conditions has proved to be an elusive goal. We have used a two-stage pernasal technique to position sensors in the human colon for the prolonged monitoring of motility in freely ambulant subjects. Nine healthy volunteers were studied for a total recording time of 263 h, each study lasting between 13 and 48 (mean 29) h. Motor activity in all regions of the large bowel was characterized by scant and irregular contractions with infrequent bursts that did not conform to any pattern. No motor coordination was apparent between different regions of the large bowel. Contractile activity throughout the large bowel was reduced to a minimum during sleep and was enhanced on waking. Meals were an inconsistent stimulus to motor activity. The technique obviates the need for colonic preparation and allows complete freedom of the subjects throughout the study. In demonstrating the practical feasibility of this mode of studying the colon, these preliminary data highlight a requirement for the availability of appropriate equipment but raise questions about the design and use of such equipment and methods of data analysis.


2015 ◽  
Vol 309 (5) ◽  
pp. G368-G376 ◽  
Author(s):  
Haifeng Jin ◽  
Jiemin Liu ◽  
Robert D. Foreman ◽  
Jiande D. Z. Chen ◽  
Jieyun Yin

Electroacupuncture (EA) has been shown to improve impaired gastric motility and slow waves in both humans and animals. However, its effects on colonic motility have rarely been investigated. The aim of this study was to investigate the effects and underlying mechanisms of EA on impaired colonic motility induced by rectal distension (RD)in dogs. Colon contractions and transit were measured in various sessions with and without EA in hound dogs chronically placed with a colonic cannula. Colonic contractile activity was assessed by motility index (MI). Autonomic functions were determined by the spectral analysis of the heart rate variability derived from the electrocardiogram. It was found 1) RD suppressed colonic motility by 40.5% (10.8 ± 0.9 with RD vs. 6.4 ± 0.8 at baseline, P < 0.002). EA at ST36 normalized colonic contractions suppressed by RD (12.9 ± 2.8, P < 0.002 vs. RD and P = 0.1 vs. control). 2) Administration of atropine blocked the ameliorating effect of EA on colon motility. 3) RD also delayed colonic transit (65.0 ± 2.0% with RD vs. 86.0 ± 1.9% without RD, P < 0.001) that was restored with EA (84.0 ± 1.9%, P = 0.178 vs. control). 4) EA increased vagal activity suppressed by RD (0.37 ± 0.07 with RD + EA vs. 0.09 ± 0.03 with RD without EA, P < 0.001). In conclusion, RD inhibits colonic contractions and delays colonic transit in dogs; EA at ST36 restores the RD-induced impairment in both colonic contraction and transit by enhancing vagal activity and mediated via the cholinergic pathway.


1993 ◽  
Vol 265 (4) ◽  
pp. G767-G774 ◽  
Author(s):  
J. C. Eagon ◽  
K. A. Kelly

Gastric pacing has been achieved in dogs and humans, but its effects on gastric motility and emptying have not been thoroughly explored. Seven dogs had bipolar electrodes placed 1 and 10 cm proximal to the pylorus for reverse and forward pacing and monopolar recording electrodes and strain gauges placed 3, 5, and 7 cm proximal to the pylorus. After recovery, myoelectrical and contractile activity and gastric emptying of a mixed meal (50 g 99mTc-labeled liver and 250 ml 111In-labeled 5% dextrose broth solution) were measured in each of three conditions: no pacing, reverse pacing, and forward pacing (frequency 0.5 cycles/min above intrinsic pacesetter potential frequency). Reverse pacing reversed the direction of > 90% of antral pacesetter potentials and peristaltic waves in six of seven dogs, prolonged the lag phase of solid emptying, prolonged the half emptying time of solids and liquids, and increased the antral motility index. Forward pacing entrained pacesetter potentials but had no consistent effect on emptying or antral contractions. In conclusion, reverse gastric pacing slows gastric emptying of digestible solids and liquids by reversing the direction of antral peristalsis and increasing the antral motility index, whereas forward pacing has no such effects.


2021 ◽  
pp. 089719002110215
Author(s):  
Sara A. Atyia ◽  
Keaton S. Smetana ◽  
Minh C. Tong ◽  
Molly J. Thompson ◽  
Kari M. Cape ◽  
...  

Background: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that produces dose-dependent sedation, anxiolysis, and analgesia without respiratory depression. Due to these ideal sedative properties, there has been increased interest in utilizing dexmedetomidine as a first-line sedative for critically ill patients requiring light sedation. Objective: To evaluate the ability to achieve goal intensive care unit (ICU) sedation before and after an institutional change of dosing from actual (ABW) to adjusted (AdjBW) body weight in obese patients on dexmedetomidine. Methods: This study included patients ≥ 18 years old, admitted to a surgical or medical ICU, required dexmedetomidine for at least 8 hours as a single continuous infusion sedative, and weighed ≥ 120% of ideal body weight. Percentage of RASS measurements within goal range (−1 to +1) during the first 48 hours after initiation of dexmedetomidine as the sole sedative agent or until discontinuation dosed on ABW compared to AdjBW was evaluated. Results: 100 patients were included in the ABW cohort and 100 in the AdjBW cohort. The median dosing weight was significantly higher in the ABW group (95.9 [78.9-119.5] vs 82.2 [72.1-89.8] kg; p = 0.001). There was no statistical difference in percent of RASS measurements in goal range (61.5% vs 69.6%, p = 0.267) in patients that received dexmedetomidine dosed based on ABW versus AdjBW. Conclusion: Dosing dexmedetomidine using AdjBW in obese critically ill patients for ongoing ICU sedation resulted in no statistical difference in the percent of RASS measurements within goal when compared to ABW dosing. Further studies are warranted.


1989 ◽  
Vol 67 (6) ◽  
pp. 553-560 ◽  
Author(s):  
R. B. Scott ◽  
D. G. Gall ◽  
S. C. Diamant

To determine if Yersinia enterocolitica (YE) enteritis is associated with an alteration of intestinal myoelectric and motor activity, and with an increased rate of aboral transit, New Zealand white rabbits (500–900 g) were surgically prepared with ileal bipolar electrodes and a manometry catheter adjacent to the distal electrode. One week later animals were inoculated with 1010 organisms of YE in 10 mL NaHCO3 (infected group) or 10 mL NaHCO3 (sham-infected pair-fed and control groups). Daily food intake, weight gain, YE excretion, and stool pattern were noted. Intestinal myoelectric and motor activity over a 6- to 8- h period before and 3, 6, and 14 days after inoculation was compared in infected (I), pair-fed (PF), and control (C) groups. Intestinal transit was evaluated in I and C animals on days 3 and 6 after inoculation by measuring the distribution in the intestinal lumen of 51Cr 20 min after it was instilled directly into the jejunum. Infected animals exhibited diarrhea, fecal excretion of YE, and significantly decreased food intake, weight gain, and survival (11.4 ± 0.6 days). Infection was associated with a significant (p < 0.05) decrease in both the cycle period of the migrating myoelectric complex (MMC) and the total number of single, paired, and (or) clustered contractions per MMC, and a significant (p < 0.001) increase in duration of phase III of the MMC. There was no change in intestinal slow wave frequency (19 cycles/min), motility index per MMC, or the percentage of contractions that propagated in an orad (7%) or aboral (69%) direction or that appeared stationary (25%). The changes in myoelectric and motor activity were specific for YE infection (not related to decreased food intake and weight gain) and were associated with a significantly increased rate of aboral transit. Thus, the inflammatory enteritis induced by YE is associated with alterations of intestinal myoelectric and motor activity, and an increased rate of aboral transit.Key words: Yersinia enterocolitica, infection, intestine, motility, transit.


2003 ◽  
Vol 37 (2) ◽  
pp. 178-181 ◽  
Author(s):  
Hideko Tanaka ◽  
Kana Matsumoto ◽  
Kazuyuki Ueno ◽  
Mayumi Kodama ◽  
Kohji Yoneda ◽  
...  

OBJECTIVE: To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors. METHODS: Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin. RESULTS: Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 ± 0.329 ng/mL; after, 1.36 ± 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration. CONCLUSIONS: Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.


2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.


Sign in / Sign up

Export Citation Format

Share Document