Evaluation of Neuromuscular Blockade Reversal on Postoperative Mechanical Ventilation Time in a Cardiovascular Surgery Population.

OBJECTIVE: To report on postoperative outcomes related to the administration of neostigmine for reversal of nondepolarizing neuromuscular blocking agents in cardiovascular surgery patients, with a specific focus on the duration of postoperative mechanical ventilation as the primary endpoint. DESIGN: A retrospective cohort study design was followed to achieve the study objectives. SETTING: This was a single-center, chart review study conducted at a large academic medical center of adult patients post-cardiovascular surgery. PARTICIPANTS: Patients were included if they had received a bolus dose of perioperative nondepolarizing neuromuscular blocking agent and underwent one of the targeted cardiovascular surgeries. INTERVENTIONS: Final analysis comprised of 175 patients, 95 of whom received neostigmine and 80 who did not receive neostigmine. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the duration of postoperative mechanical ventilation. When controlling for all covariates, neostigmine use was associated with a 0.34-hour reduction (∼20.4 min) in duration of mechanical ventilation (parameter estimate: 0.66, 95% confidence interval 0.49-0.89; p = 0.0071). More patients who received neostigmine met the early extubation benchmark of less than 6 hours (55 v 34 patients; p = 0.04). Finally, neostigmine use was not found to be associated with increased risk of respiratory complications or postoperative nausea and/or vomiting. CONCLUSIONS: The use of neostigmine was found to have a protective effect on the duration of postoperative mechanical ventilation without increasing the risk of adverse complications.

Possible role of hydrogen sulfide as an endogenous relaxation factor in the rat bladder and prostate.

AIMS: To clarify the roles of hydrogen sulfide (H2 S), an endogenous gasotransmitter, in the rat bladder and prostate, we investigated the distribution of enzymes related to H2 S biosynthesis (cystathionine ß-synthase [CBS], cystathionine γ-lyase [CSE], 3-mercaptopyruvate sulfurtransferase [MPST], cysteine aminotransferase [CAT], and D-amino acid oxidase [DAO]) and the content of H2 S. We also investigated the effects of H2 S donors (NaHS and GYY4137) on the contractility of both tissues and on micturition. METHODS: The distribution of these enzymes was investigated by real-time PCR, Western blot, and immunohistochemistry. Tissue H2 S content was measured by the methylene blue method. The effects of NaHS (1 × 10-9 to 3 × 10-4 M) were evaluated on carbachol (10-5 M)-induced pre-contracted bladder strips, and on noradrenaline (10-5 M)-induced pre-contracted prostate strips, which were pretreated with propranolol (10-6 M). In addition, in urethane-anesthetized male Wistar rats, the effects of intravesically instilled GYY4137 (10-8 , 10-7 , and 10-6 M) on micturition were evaluated by cystometry. RESULTS: MPST and CAT were detected in the bladder and prostate, CBS was only detected in the prostate, while CSE and DAO were not detected in both tissues. Immunoreactivity of these enzymes was mainly detected in the urothelium and smooth muscle layer of the bladder and in the prostate glandular epithelium. H2 S was detected in both tissues. NaHS dose-dependently induced relaxation of pre-contracted bladder and prostate strips. Intravesically instilled GYY4137 significantly prolonged intercontraction intervals. CONCLUSIONS: It is possible that H2 S can function as an endogenous relaxation factor in the rat bladder and prostate.

Are There Pharmacotherapeutic Options for Underactive Bladder?

Currently, underactive bladder, the symptom-based correlate of the urodynamic diagnosis of detrusor underactivity, has no effective drug treatments. Use of sympathomimetics, targeting cholinergic receptors, is not supported by current evidence. Several potential targets are the subject of ongoing investigation.

Sudden-onset unilateral ptosis induced by pituitary Macroadenoma, with false-positive jolly and neostigmine tests.

The development of ptosis as a consequence of pituitary tumor is an exceptionally rare occurrence. Here, we describe the case of sudden-onset unilateral ptosis induced by pituitary macroadenoma. The condition was characterized by false-positive Jolly and neostigmine tests. These findings mimic oculomotor nerve palsy and make the correct diagnostics rather challenging. The case points to the fact that patients with acquired ptosis need detailed neuroophthalmological examination.

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers.SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system.

Regulating autonomic nervous system homeostasis improves pulmonary function in rabbits with acute lung injury.

BACKGROUND: This study aimed to investigate the effects of regulating autonomic nervous system (ANS) homeostasis by inhibiting sympathetic hyperactivity and/or enhancing parasympathetic activity on pulmonary inflammation and functional disturbance. METHODS: An animal model of acute lung injury (ALI) was established in rabbits by an intratracheal injection of hydrochloric acid (HCl) in rabbits. Animals in control groups were received saline or HCl only, and the others received both HCl and followed treatments: vagus nerve stimulation (VNS), intravenous injection of tetrahydroaminoacridine (THA), or stellate ganglion block (SGB). The effects of different treatments on the changes in autonomic nervous system homeostasis, pulmonary and systemic inflammation, and functional disturbance were detected. RESULTS: Sympathetic nervous activity was higher than parasympathetic nervous activity in rabbits after HCl aspiration, as demonstrated by the significant changes in the discharge frequency of cervical sympathetic/vagus trunk, and heart rate variability. VNS, THA and SGB could significantly alleviate the changes of ANS induced by HCl aspiration and improved the pulmonary function, especially for SGB treatment. CONCLUSIONS: The disturbance of ANS homeostasis is attributed to a predominance of SNS activity. Administration of VNS, THA and SGB are capable to regulate disequilibrium of the ANS in rabbits with HCl-induced ALI and SGB is supposed to be the most effective approach.

Effects of cevimeline on excitability of parasympathetic preganglionic neurons in the superior salivatory nucleus of rats.

The superior salivatory nucleus (SSN) contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, is a sialogogue that possibly stimulates SSN neurons in addition to the salivary glands themselves because it can cross the blood-brain barrier (BBB). In the present study, we examined immunoreactivities for mAChR subtypes in SSN neurons retrogradely labeled with a fluorescent tracer in neonatal rats. Additionally, we examined the effects of cevimeline in labeled SSN neurons of brainstem slices using a whole-cell patch-clamp technique. Mainly M1 and M3 receptors were detected by immunohistochemical staining, with low-level detection of M4 and M5 receptors and absence of M2 receptors. Most (110 of 129) SSN neurons exhibited excitatory responses to application of cevimeline. In responding neurons, voltage-clamp recordings showed that 84% (101/120) of the neurons exhibited inward currents. In the neurons displaying inward currents, the effects of the mAChR antagonists were examined. A mixture of M1 and M3 receptor antagonists most effectively reduced the peak amplitude of inward currents, suggesting that the excitatory effects of cevimeline on SSN neurons were mainly mediated by M1 and M3 receptors. Current-clamp recordings showed that application of cevimeline induced membrane depolarization (9/9 neurons). These results suggest that most SSN neurons are excited by cevimeline via M1 and M3 muscarinic receptors.

Epidural Neostigmine versus Fentanyl to Decrease Bupivacaine Use in Patient-controlled Epidural Analgesia during Labor: A Randomized, Double-blind, Controlled Study.

BACKGROUND: The addition of opioids to epidural local anesthetic reduces local anesthetic consumption by 20% but at the expense of side effects and time spent for regulatory compliance paperwork. Epidural neostigmine also reduces local anesthetic use. The authors hypothesized that epidural bupivacaine with neostigmine would decrease total hourly bupivacaine use compared with epidural bupivacaine with fentanyl for patient-controlled epidural analgesia. METHODS: A total of 215 American Society of Anesthesiologists physical status II, laboring parturients requesting labor epidural analgesia consented to the study and were randomized to receive 0.125% bupivacaine with the addition of either fentanyl (2 µg/ml) or neostigmine (2, 4, or 8 µg/ml). The primary outcome was total hourly local anesthetic consumption, defined as total patient-controlled epidural analgesia use and top-ups (expressed as milliliters of 0.125% bupivacaine) divided by the infusion duration. A priori analysis determined a group size of 35 was needed to have 80% power at α = 0.05 to detect a 20% difference in the primary outcome. RESULTS: Of 215 subjects consented, 151 patients were evaluable. Demographics, maternal and fetal outcomes, and labor characteristics were similar among groups. Total hourly local anesthetic consumption did not differ among groups (P = 0.55). The total median hourly bupivacaine consumption in the fentanyl group was 16.0 ml/h compared with 15.3, 14.6, and 16.2 ml/h in the 2, 4, and 8 µg/ml neostigmine groups, respectively (P = 0.55). CONCLUSIONS: The data do not support any difference in bupivacaine requirements for labor patient-controlled epidural analgesia whether patients receive epidural bupivacaine with 2 to 8 µg/ml neostigmine or epidural bupivacaine with 2 µg/ml fentanyl.

Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.

Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α2-adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg-1) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (P<0.01). In rats with vagotomy (n=5), DMI did not significantly change ACh (from 0.92±0.16 to 0.85±0.23nM). In rats with intact vagi pretreated with intravenous yohimbine (2mg·kg-1), DMI did not significantly change ACh (from 1.25±0.23 to 1.13±0.15nM). In conclusion, while DMI is generally considered to be an agent that predominantly affects sympathetic neurotransmission, it can activate the cardiac vagal nerve via α2-adrenergic stimulation in experimental settings in vivo.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.

Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke.

BACKGROUND AND PURPOSE: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. METHODS: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity. RESULTS: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung. CONCLUSIONS: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.

Effect of galantamine on adjuvant-induced arthritis in rats.

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis.

Effect of orally administered cisapride, bethanechol, and erythromycin on the apparent efficiency of colostral IgG absorption in neonatal Holstein-Friesian calves.

OBJECTIVE: To evaluate the effect of orally administered cisapride, bethanechol, and erythromycin on the absorption of colostral IgG in dairy calves. ANIMALS: Twenty-four healthy neonatal Holstein-Friesian calves. PROCEDURES: Calves were randomly assigned to one of the following treatments: 0.9% NaCl solution (2 mL, p.o.; negative control); erythromycin lactobionate (20 mg/kg BW, p.o.; anticipated to be a positive control); cisapride (0.5 mg/kg BW, p.o.); bethanechol chloride (0.5 mg/kg BW, p.o.). Calves were fed 3 L of pooled bovine colostrum containing acetaminophen (50 mg/kg) by suckling and oroesophageal intubation 30 minutes after each treatment was administered. Jugular venous blood samples were obtained periodically after the start of feeding and plasma total IgG, protein, acetaminophen, and glucose concentrations determined. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. RESULTS: Oral administration of cisapride facilitated the absorption of colostral IgG and protein. The effect of cisapride on abomasal emptying rate could not be evaluated because cisapride appeared to interfere with acetaminophen metabolism. Based on the total IgG and total protein concentration-time relationships, the beneficial effects of cisapride appeared to occur early after oral administration and were transient. CONCLUSIONS AND CLINICAL IMPORTANCE: Additional studies appear indicated to characterize the effect of cisapride dose on the magnitude and duration of its effect on facilitating the absorption of colostral IgG and protein. Identification of a nonantimicrobial method for increasing abomasal emptying rate, such as cisapride, will potentially provide a practical and effective method for facilitating transfer of passive immunity in colostrum-fed dairy calves.

Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects.

BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 µg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1-0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch(®) SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 µg/kg plus atropine 10-20 µg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3-1.5) min and 6.7 (5.5-8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB. CONCLUSION: Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 µg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00825812.

[Effect of galantamine and testosterone on the arthritic response and dopamine content in rat spleen].

The study was carried out on male Wistar rats with surgically ablated gonads. The rats with gonadectomy and intact rats received galantamine and/or testosterone over 10 days, after which the model arthritis was induced by injection of 200 ml of complete Freund's adjuvant. It was established that gonadectomy reduced arthritic reactions producing ulcer formation at a later time (21 days) as compared to control (rats with arthritis), where they are formed on the local stage of development (day 7). Testosterone replacement therapy completely blocks the development of ulcers on the paws. Galantamine suppresses the arthritic reaction more significantly, reducing paws and ankle-joint edema 1.5 and 1.3 times respectively (n = 12, p <0.05). The appearance of dopamine in the spleen during galantamine treatment may serve as a marker of protective action of the drug under hypoandrogenic conditions. Introduction of galantamine at high level of testosterone does not significantly influence on development of arthritic reaction, which is indicative of a marked imbalance between the hormonal and cholinergic systems and a possibility to modulate arthritic reaction with cholinergic drugs.

Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction.

Myocardial infarction (MI) is associated with remodeling of the heart and neurohumoral control systems. The objective of this study was to define time-dependent changes in intrinsic cardiac (IC) neuronal excitability, synaptic efficacy, and neurochemical modulation following MI. MI was produced in guinea pigs by ligation of the coronary artery and associated vein on the dorsal surface of the heart. Animals were recovered for 4, 7, 14, or 50 days. Intracellular voltage recordings were obtained in whole mounts of the cardiac neuronal plexus to determine passive and active neuronal properties of IC neurons. Immunohistochemical analysis demonstrated an immediate and persistent increase in the percentage of IC neurons immunoreactive for neuronal nitric oxide synthase. Examination of individual neuronal properties demonstrated that after hyperpolarizing potentials were significantly decreased in both amplitude and time course of recovery at 7 days post-MI. These parameters returned to control values by 50 days post-MI. Synaptic efficacy, as determined by the stimulation of axonal inputs, was enhanced at 7 days post-MI only. Neuronal excitability in absence of agonist challenge was unchanged following MI. Norepinephrine increased IC excitability to intracellular current injections, a response that was augmented post-MI. Angiotensin II potentiation of norepinephrine and bethanechol-induced excitability, evident in controls, was abolished post-MI. This study demonstrates that MI induces both persistent and transient changes in IC neuronal functions immediately following injury. Alterations in the IC neuronal network, which persist for weeks after the initial insult, may lead to alterations in autonomic signaling and cardiac control.

Global small bowel motility: assessment with dynamic MR imaging.

PURPOSE: To assess the repeatability in human volunteers of software-quantified small bowel motility captured with magnetic resonance (MR) imaging and to test the ability to detect changes in motility induced by pharmacologic agents. MATERIALS AND METHODS: The study was approved by the Royal Free Research Ethics Committee, and all subjects gave full written informed consent. Twenty-one healthy volunteers (14 men, seven women; mean age, 28 years) underwent cine MR imaging with a three-dimensional balanced turbo field-echo sequence to capture small bowel motility. Volume blocks (15 cm thick) were acquired every second during a 20-second breath hold. A randomized, blinded, placebo-controlled crossover study of either 0.5 mg neostigmine or saline (n = 11) or 20 mg intravenous butylscopolamine or saline (n = 10) was performed with motility MR imaging at baseline and repeated at a mean of 4 weeks (range, 2-7 weeks). Two readers independently drew regions of interest around the small bowel, and motility was quantified by using a registration algorithm that provided a global motility metric in arbitrary units. Repeatability of the motility measurements at baseline was assessed by using Bland-Altman and within-subject coefficient of variation measures. Changes in mean motility measurements after drug administration were compared with those after placebo administration by using paired t testing. RESULTS: The repeatability between baseline measurements of motility was high; the Bland-Altman mean difference was -0.0025 (range, 0.28-0.4), the 95% limit of agreement was ±0.044 arbitrary units (au), and the within-subject coefficient of variation was 4.9%. Measured motility with neostigmine (mean, 0.39 au) was significantly higher than that with placebo (mean, 0.34 au; P < .001), whereas that with butylscopolamine (mean, 0.13 au) was significantly lower than that with placebo (mean, 0.30 au; P < .001). CONCLUSION: Quantification of small bowel motility with use of MR imaging in healthy volunteers is repeatable and sensitive to changes induced by means of pharmacologic manipulation. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130151/-/DC1.