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.

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.

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.

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.

Intravenous regional anesthesia using lidocaine and neostigmine for upper limb surgery.

STUDY OBJECTIVE: To evaluate the effect of adding neostigmine to lidocaine in intravenous regional anesthesia (IVRA). DESIGN: Randomized, double-blinded study. SETTING: Tertiary-care academic medical institution. PATIENTS: 40 ASA physical status I and II patients scheduled for elective or emergency forearm and hand surgery. INTERVENTION: Patients were randomized to two groups of 20 patients each. In the control group, IVRA was established using 40 mL of 0.5% lidocaine with one mL of isotonic saline, while neostigmine group patients received 40 mL of 0.5% lidocaine with 0.5 mg neostigmine. MEASUREMENTS: Hemodynamic parameters, onset and recovery times of sensory and motor blocks, and quality of anesthesia achieved with IVRA were recorded. After tourniquet deflation, visual analog pain scores (VAS) were noted every 30 minutes in the first two hours, as were the time to first analgesic request and total analgesic requirement in the 24-hour postoperative period. MAIN RESULTS: In the first 24 hours after surgery, the neostigmine group had significantly lower VAS scores, longer time to first analgesic request, and reduced total analgesic requirement. Intraoperatively, the neostigmine group had significantly shorter sensory and motor block onset times and longer recovery times than the control group. No significant frequency of adverse effects was seen in either group. The quality of intraoperative anesthesia and frequency of tourniquet pain were similar in both groups. CONCLUSIONS: The addition of neostigmine to lidocaine shortens onset time and improves postoperative analgesia in IVRA for upper limb surgery.

Pharmacotherapy of intraocular pressure: part I. Parasympathomimetic, sympathomimetic and sympatholytics.

Elevated intraocular pressure (IOP) has been recognized as the major risk factor for the development of glaucoma and a wide range of options are now available to reduce it: medical treatment, laser, filtering, or cyclodestructive surgery (alone or in combination). All these modalities act by decreasing eye pressure and, thereby, protecting the optic nerve head from a mechanic direct and/or vascular indirect insult. Topical medical therapy represents the first-choice treatment and, in most cases, it effectively controls IOP, avoiding the occurrence of further optic nerve damage. All medications lower IOP in two main ways: decreasing the production of aqueous humour or by increasing its outflow from the eye. Consequently, antiglaucoma drugs either suppress aqueous humour formation (beta-adrenergic antagonists, carbonic anhydrase inhibitors, and alpha-2-adrenergic agonists) or raise aqueous humour outflow throughout the conventional (e.g., pilocarpine) or uveoscleral (prostaglandin FP receptor agonists, and prostamides) route. In addition, fixed and unfixed combinations of antiglaucoma compounds have also been available for patients requiring more than one type of medication. This review, which is part one of two (please see Expert Opinion on Pharmacotherapy 10 (17)) briefly considers the characteristics of sympathomimetic, sympatholytics and parasympathomimetic commonly employed in the medical treatment of glaucoma, mainly the primary open-angle form, focusing the discussion on the clinical evidence supporting the use of these three classes of compound.

Nicotine-induced neurogenic relaxation in the mouse colon: changes with dextran sodium sulfate-induced colitis.

Nicotine has been shown to reduce both tone and muscular activity in the human colon by releasing nitric oxide (NO) from nerves. To our knowledge, however, the effect of nicotine on mouse colon has not been elucidated, and the response in tissue from ulcerative colitis (UC) has not been investigated. We examined nicotine-induced responses in colon from control mice and mice with dextran sodium sulfate (DSS)-induced UC. In controls, bath application of nicotine caused a transient relaxation in longitudinal preparations from the transverse and distal colons but not from the rectum. The response was observed in the presence of bethanechol, abolished by treatment with tetrodotoxin and hexamethonium, and mediated partially (>50%) by the NO pathway. In longitudinal preparations of the distal colon from DSS-treated mice, spontaneous contractions decreased markedly, and nicotine caused contraction without relaxation in half of the preparations tested. Nicotine-induced relaxation in the presence of bethanechol was significantly decreased in the DSS-treated distal colon without changing bethanechol-induced contractions. These data suggest that 1) responses to nicotine differ dependent on colon regions, 2) DSS treatment predominantly caused nicotine-sensitive neurogenic changes in distal colon, and 3) DSS treatment may reverse the direction of nicotine-evoked responses in the colon, in mice.

Hoarseness as a sign of possible nonspecific mucosal hyperreactivity in vocal tract.

The aim of the present paper was to evaluate the possible impact of methacholine challenge on the voice and vocal tract in 10 patients reporting hoarseness due to presumable hyperreactivity to some environmental factors. Ten age and gender-matched healthy subjects served as controls. Methacholine was used for hypersensitivity challenge and saline solution (0.9% NaCl) as control substance. Subjects were examined on two separate challenge occasions testing either methacholine in increasing doses (3, 6, 12 mg) or NaCl. Voice recordings, videolaryngoscopy, and measurement of nasal secretion were performed before and after each sniffing session. Subjective complaints were documented. Data were statistically analyzed with three-way analysis of variance and group comparisons performed. Perceptual analysis of voice recordings showed an increase of the grade of voice disorder in patients after exposure to both substances. Moreover, one of the patients became aphonic and another severely dysphonic after NaCl. No voice quality changes were detected in controls. The videolaryngoscopy findings divergent from normal did not increase in any group. Nasal secretion was significantly higher after sniffing of methacholine than NaCl in both groups. The frequency of subjective complaints was equal in both groups after both substances. However, there was a qualitative difference in the character of the symptoms: the patients complained of throat, vocal, and nasal symptoms whereas the controls complained exclusively of nasal symptoms. The study supports the view that vocal dysfunction after exposure to non-specific environmental irritating factors may be triggered mainly by emotional mechanisms such as off-warding reaction or dissociative disorder.

Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation.

OBJECTIVE: The commonly associated aetiology of salivary gland inflammation and salivary hypofunction has led to the widely held belief that inflammation causes salivary gland hypofunction. Indeed, our own recent study seemed to support this contention. Here, we tested the hypothesis that, in an acute duct ligation model, eliminating inflammation the submandibular gland would recover normal function. MATERIALS AND METHODS: Ligation of the rat submandibular gland excretory duct for 24 h was used to induce inflammation and salivary gland hypofunction. A group of duct ligated rats was compared with a second group given dexamethasone, on the day of duct ligation. Twenty-four hours later salivary gland function was assessed and salivary glands were collected. RESULTS: Histology and myeloperoxidase activity assay revealed a profound decrease in inflammatory cell infiltration of ligated glands from rats given dexamethasone, compared with ligated glands in the absence of dexamethasone. Salivary flow rate evoked by methacholine was decreased (P < 0.01) by approximately 56% (ligated vs control, 79 +/- 9 microl min(-1) g(-1)vs 177 +/- 11 microl min(-1) g(-1)) and salivary flow from ligated dexamethasone-treated and ligated glands was similar. CONCLUSION: Despite eliminating the inflammatory reaction in the ligated gland, salivary hypofunction was not reversed, suggesting that other mechanisms must be at work in the ligation-induced salivary hypofunction.

Neostigmine and pilocarpine attenuated tumour necrosis factor alpha expression and cardiac hypertrophy in the heart with pressure overload.

The inflammatory cytokine tumour necrosis factor alpha (TNF alpha) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF alpha expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine, and a muscarinic cholinergic agonist, pilocarpine, on cardiac hypertrophy and TNF alpha levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF alpha protein levels in the heart, increased heart weight to body weight ratios (an index of cardiac hypertrophy) and decreased left ventricular diastolic function. Two weeks of infusion with neostigmine (6 microg kg(-1) day(-1)) or pilocarpine (0.3 mg kg(-1) day(-1)) significantly reduced cardiac hypertrophy, reduced TNF alpha levels and elevated interleukin-10 levels in heart tissues, and improved ventricular function in rats with transverse aortic constriction. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with pilocarpine attenuated adrenergic agonist phenylephrine-induced increased TNF alpha expression and [3H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF alpha levels and attenuated cardiac hypertrophy. Since both agents potentially enhanced cholinergic function, the anti-inflammatory action may be involved in the cardioprotective effect of the treatments with these agents.

Changes in functional properties of the caffeine-sensitive Ca2+ store during differentiation of human SH-SY5Y neuroblastoma cells.

We have used single cell fluorescence imaging techniques to examine how functional properties of the caffeine-sensitive Ca(2+) store change during differentiation of a sub-population of caffeine-sensitive SH-SY5Y cells. Application of caffeine (30 mM) 1-10.5 min after a 'priming' depolarisation pulse of 55 mM K(+) revealed that the caffeine-sensitive store in undifferentiated cells remained replete, whereas that in 9-cis retinoic acid (9cRA)-differentiated cells spontaneously dissipated with a t(1/2) of 2.8 min, and was essentially completely depleted approximately 10 min after priming. In 9cRA-differentiated cells that were stimulated with methacholine (10 microM) 1 min after priming, the amplitude, rate of rise and propagation velocity of the Ca(2+) wave in the neurites were all constant, whereas these kinetic parameters all progressively decreased as the wave travelled along the neurites in cells that were stimulated 10 min after priming. Use-dependent block with ryanodine inhibited the global Ca(2+) signal in 9cRA-differentiated cells stimulated with methacholine 1 min after priming (71+/-8%) but not 10 min after priming. Depolarisation was more effective at priming the caffeine-sensitive Ca(2+) store in 9cRA-differentiated cells, which lack a functional store-operated Ca(2+) entry pathway. We conclude that differentiation of caffeine-sensitive SH-SY5Y cells is accompanied by an increase in lability of the caffeine-sensitive Ca(2+) store, and that spontaneous dissipation of Ca(2+) from the store limits the time course of its molecular 'memory' during which it can amplify the hormone-induced Ca(2+) signal by Ca(2+)-induced Ca(2+) release.

Inhibition of salivary secretion by activation of cannabinoid receptors.

It is known that marijuana use decreases saliva secretion. Therefore, we hypothesized that cannabinoid receptors (CBs) are located in salivary glands to mediate that effect. In these experiments, we used the submandibular gland (SMG) of male rats, which is one of the major salivary glands. Mammalian tissues contain at least two types of CBs, CB1 and CB2, mainly located in the nervous system and peripheral tissues, respectively. Both receptors are coupled to Gi protein and respond by inhibiting the activity of adenylyl cyclase. We demonstrated that both CB1 and CB2 are present in the SMG, each showing specific localizations. The best-known endocannabinoid is anandamide (AEA), which binds with high affinity to CB1 and CB2. We showed that AEA markedly reduced forskolin-induced increase of cAMP content in vitro. This effect was blocked by AM251 and AM630 (CB1 and CB2 antagonists, respectively), indicating that both receptors are implicated in SMG physiology. In addition, we showed that AEA injected intraglandularly to anesthetized rats inhibited norepinephrine (NE)- and methacholine (MC)-stimulated saliva secretion in vivo and that both AM251 or AM630 prevented the inhibitory action of AEA. Also, the intraglandular injection of AM251 increased saliva secretion induced by lower doses of NE or MC. This increase was synergized after coinjection with AM630. Therefore, we concluded that AEA decreases saliva secretion in the SMG acting through CB1 and CB2 receptors.

Intestinal ischemia/reperfusion injury aggravates talc-induced adhesions in rats.

BACKGROUND: Postoperative intraperitoneal adhesions are the leading cause of intestinal obstruction, but the underlying mechanisms remain incompletely understood. The aim of the current study was to investigate the involvement of intestinal ischemia/reperfusion (I/R) injury in adhesion formation in rats. MATERIALS AND METHODS: Rats were subjected to either a dusting of talc (15 mg/rat) over the entire small intestine or ischemia induced by clamping the superior mesenteric artery (SMA) for 30 min followed by reperfusion with or without talc dusting. On postoperative days 4, 7, and 14, the scores, lengths, and incidence of adhesions were evaluated. In addition, the contractile force of the jejunal muscle was measured at 0, 24, 48, and 96 h after the treatments using organ bath techniques under bethanechol-stimulated conditions. RESULTS: Talc induced mild adhesions in rats. Although I/R injury alone did not produce adhesions, it markedly aggravated the talc-induced adhesions, with higher scores and longer adhesions on postoperative days 4, 7, and 14. In addition, I/R injury caused 75-88% suppression of the circular muscle contractile force and 35-52% suppression of the longitudinal muscle contractile force at 24 h after SMA occlusion. However, talc did not affect the contractions. CONCLUSIONS: Intestinal I/R injury aggravated the talc-induced adhesions, and this consequence might be due to the functional suppression of jejunal muscle contractions. This finding suggests that intestinal ischemia is an important factor in the etiology of postoperative adhesions.