The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

The role of vasoactive intestinal peptide (VIP) in atropine-related inhibition of the progression of myopia.

OBJECTIVE: This study aimed to investigate the potential involvement of vasoactive intestinal polypeptide (VIP) in myopia development and its contribution to the mechanism of action of the anti-myopia drug, atropine. METHODS: Thirty-three-week-old guinea pigs were randomly divided into normal control (NC, n = 10), monocularly form-deprived (FDM, n = 10), and FDM treated with 1% atropine (FDM + AT, n = 10) groups. The diopter and axial length were measured at 0, 2, and 4 weeks. Guinea pig eyeballs were removed at week four, fixed, and stained for morphological changes. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to evaluate VIP protein and mRNA levels. RESULTS: The FDM group showed an apparent myopic shift compared to the control group. The results of the H&E staining were as follows: the cells of the inner/outer nuclear layers and retinal ganglion cells were disorganized; the choroidal thickness (ChT), blood vessel lumen, and area were decreased; the sclera was thinner, with disordered fibers and increased interfibrillar space. IHC and ISH revealed that VIP's mRNA and protein expressions were significantly up-regulated in the retina of the FDM group. Atropine treatment attenuated FDM-induced myopic shift and fundus changes, considerably reducing VIP's mRNA and protein expressions. CONCLUSIONS: The findings of elevated VIP mRNA and protein levels observed in the FDM group indicate the potential involvement of VIP in the pathogenesis and progression of myopia. The ability of atropine to reduce this phenomenon suggests that this may be one of the molecular mechanisms for atropine to control myopia.

[Preventive effect of atropine premedication on vagal reflex in patients undergoing suspension laryngoscopy during anesthesia induction].

Objective: To evaluate the preventive effect of atropine premedication during anesthesia induction on vagal reflex in patients undergoing suspension laryngoscopy. Methods: A total of 342 patients (202 males and 140 females) scheduled for suspension laryngoscopy under general anesthesia in Beijing Tongren Hospital from October 2021 to March 2022 were prospectively enrolled, with a mean age of (48.1±11.9) years. The patients were randomly divided into two groups using the random number table method: the treatment group (n=171) and the control group (n=171). Patients in the treatment group were administrated with 0.5 mg atropine intravenously guttae (ivgtt) while patients in the control group were given equivalent volume of normal saline. For all patients, if heart rate (HR)<50 beats/min happened during the insertion of the suspension laryngoscope, the operation should be stopped and the laryngoscope should be removed. Patients without HR recovery after the removal of the laryngoscope should be given 0.5 mg atropine, and the operation should be continued after the HR recovered. The primary outcome was the incidence of HR fluctuation over 20% (ΔHR>20%) before and immediately after suspension laryngoscope fixation, and the secondary outcomes included HR, mean arterial pressure (MAP) of the two groups recorded before and after anesthesia induction, before and immediately after suspension laryngoscope fixation, and the incidences of sinus bradycardia, laryngoscope removal and atropine treatment during operation. Results: The incidences of ΔHR>20% and bradycardia immediately after the suspension laryngoscope fixation were 14.6% (25/171) and 12.9% (22/171) in the treatment group, which were significantly lower than those in the control group [28.1% (48/171) and 29.8% (51/171)] (both P<0.05). The HR immediately after the suspension laryngoscope fixation in the treatment group [(66.4±13.5) beats/min] and in the control group [(60.8±15.7) beats/min] was significantly lower than those before the suspension laryngoscope fixation [(74.7±11.1) beats/min and (67.6±12.8) beats/min, respectively] (both P<0.05). There were no significant differences in MAP between the two groups at each time point (all P>0.05). The incidence of laryngoscope removal once plus 0.5 mg atropine administration, laryngoscope removal twice plus 0.5 mg atropine administration and laryngoscope removal twice plus 1.0 mg atropine administration was 9.9% (17/171), 1.8% (3/171) and 0 (0) in the treatment group, respectively, which was significantly lower than those in the control group [24.0% (41/171), 5.8% (10/171) and 2.3% (4/171), respectively] (all P<0.05). Conclusion: Atropine premedication during anesthesia induction can effectively reduce the occurrence of vagal reflex in patients undergoing suspension laryngoscopy.

Effects of atropine and tropicamide on ocular biological parameters in children: a prospective observational study.

BACKGROUND: The effectiveness of cycloplegia in delaying the progression of myopia and its application in refractive examination in children have been extensively studied, but there are still few studies on the effects of atropine/tropicamide on ocular biological parameters. Therefore, the purpose of this study was to explore the effects of atropine/tropicamide on children's ocular biological parameters in different age groups and the differences between them. METHODS: This was a prospective observational study in which all school children were examined for dioptres and ocular biological parameters in the outpatient clinic, and 1% atropine or tropicamide was used for treatment. After examination, we enrolled the patients grouped by age (age from 2 to 12 years treated by atropine, 55 cases; age from 2 to 10 years treated by tropicamide, 70 cases; age from 14 to 17 years treated by tropicamide, 70 cases). The ocular biological parameters of each patient before and after cycloplegia were measured, and the difference and its absolute value were calculated for statistical analysis using an independent-samples t test. RESULTS: We compared the value and the absolute value of the differences in ocular biological parameters before and after cycloplegia in the same age group, and we found that the differences were not statistically significant (P > 0.05). There were significant differences in the corresponding values of AL, K1 and ACD among the different age groups (P < 0.05). Before cycloplegia, there were significant differences in AL, K, K1, K2 and ACD in different age groups (P < 0.05). However, the differences in AL, K, K1, K2 and ACD among different age groups disappeared after cycloplegia (P > 0.05). CONCLUSIONS: This study demonstrated that atropine/tropicamide have different effects on cycloplegia in children of different ages. The effects of atropine/tropicamide on ocular biological parameters should be fully considered when evaluating the refractive state before refractive surgery or mydriasis optometry for children of different ages.

New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies.

The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropine's inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.

Suprachiasmatic nucleus and vagus nerve trigger preovulatory LH and ovulation.

In brief: In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation. Abstract: The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.

Studies on the interactions of retinal dopamine with choroidal thickness in the chicken.

PURPOSE: Recently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken. METHODS: Changes in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence. RESULTS: The choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone-injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor-positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF. CONCLUSIONS: Retinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.

Atropine Is a Suppressor of Epithelial-Mesenchymal Transition (EMT) That Reduces Stemness in Drug-Resistant Breast Cancer Cells.

Atropine (ATR) is extracted from a belladonna plant that belongs to a class of anticholinergic drugs and is therefore involved in the treatment of the overdose of cholinergic drugs or mushroom poisoning. It is a well-known blocker of muscarinic acetylcholine receptors (mAChRs) that are expressed in various tumor cells, including breast tumors from animal and human origin, but it has yet to be recommended as an anticancer drug. Our in silico docking analysis indicates that atropine has a roust virtual binding, with a stable binding energy, to two major signaling molecules involved in EMT regulation: E-cad and ZEB-2. For both, the gene and the protein expression level results show that atropine is an effective molecule in reducing epithelial-mesenchymal transition (EMT) and colony formation induced by TGF-B or carboplatin in both the mesenchymal-like cell line MDA-MB-231 and the epithelial-like cell line T47D. We conclude that atropine as a potential suppressor of EMT could be co-administrated with other chemotherapeutic drugs to reduce stemness in drug-resistant breast tumor cells.

High-concentration atropine induces corneal epithelial cell apoptosis via miR-30c-1/SOCS3.

Atropine is an anticholinergic drug widely used in the field of ophthalmology, but its abuse can cause cytotoxicity to the cornea, resulting in blurred vision. This study used cultured human corneal epithelial cells (HCECs) to investigate the mechanism of high-concentration atropine-induced cytotoxicity. HCECs were treated with different concentrations of atropine. The expression levels of microRNA (miR)-30c-1 and suppressor of cytokine signaling 3 (SOCS3) were manipulated in HCECs treated with 0.1% atropine. Cell counting kit-8 assay and flow cytometry were used to assess the viability and apoptosis of HCECs. The relationship between miR-30c-1 and SOCS3 was obtained from an online database and validated using a dual-luciferase reporter assay and RNA immunoprecipitation method. The effect of atropine on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also investigated. High-concentration atropine inhibited the viability of HCECs and promoted their apoptosis. Moreover, atropine reduced miR-30c-1 expression and increased SOCS3 expression in a dose-dependent manner. It was found that miR-30c-1 targeted SOCS3. Overexpression of miR-30c-1-reduced atropine-induced HCEC cytotoxicity, whereas upregulation of SOCS3 reversed the effects of miR-30c-1 overexpression. High-concentration atropine inhibited activation of the JAK2/STAT3 signaling pathway via miR-30c-1/SOCS3. High-concentration atropine induces HCEC apoptosis by regulating the miR-30c-1/SOCS3 axis and JAK2/STAT3 signaling pathway.

Cardioneuroablación como tratamiento del síncope reflejo: reporte de un caso

Resumen: El síncope mediado neuralmente es un trastorno causado por un reflejo autónomo anormalmente amplificado que involucra componentes tanto simpáticos como parasimpáticos. Es la causa más frecuente de síncope en personas jóvenes y su tratamiento sigue siendo un desafío, ya que no se ha demostrado que alguna terapia farmacológica prevenga por completo su recurrencia. En los últimos años ha surgido una técnica denominada cardioneuroablación, que consiste en la ablación por radiofrecuencia de los plexos ganglionares (PG) parasimpáticos, con buenos resultados a corto y largo plazo en la prevención de síncope recurrente, según los diferentes grupos de investigación. Presentamos el primer caso en Chile de un hombre joven con síncopes mediados neuralmente recurrentes que fue tratado con esta técnica en el Hospital Regional de Concepción.

Abstract: Cardioneuroablation is a novel method that can be used to treat reflex syncope. Although the experience with this technique is relatively limited it provides a more physiological way to treat this condition. The first case in Chile is herein reported along with a discussion of the subject.

Supplemental treatment to atropine improves the efficacy to reverse nerve agent induced bronchoconstriction.

Exposure to highly toxic organophosphorus compounds causes inhibition of the enzyme acetylcholinesterase resulting in a cholinergic toxidrome and innervation of receptors in the neuromuscular junction may cause life-threatening respiratory effects. The involvement of several receptor systems was therefore examined for their impact on bronchoconstriction using an ex vivo rat precision-cut lung slice (PCLS) model. The ability to recover airways with therapeutics following nerve agent exposure was determined by quantitative analyses of muscle contraction. PCLS exposed to nicotine resulted in a dose-dependent bronchoconstriction. The neuromuscular nicotinic antagonist tubocurarine counteracted the nicotine-induced bronchoconstriction but not the ganglion blocker mecamylamine or the common muscarinic antagonist atropine. Correspondingly, atropine demonstrated a significant airway relaxation following ACh-exposure while tubocurarine did not. Atropine, the M3 muscarinic receptor antagonist 4-DAMP, tubocurarine, the ß2-adrenergic receptor agonist formoterol, the Na+-channel blocker tetrodotoxin and the K+ATP-channel opener cromakalim all significantly decreased airway contractions induced by electric field stimulation. Following VX-exposure, treatment with atropine and the Ca2+-channel blocker magnesium sulfate resulted in significant airway relaxation. Formoterol, cromakalim and magnesium sulfate administered in combinations with atropine demonstrated an additive effect. In conclusion, the present study demonstrated improved airway function following nerve agent exposure by adjunct treatment to the standard therapy of atropine.

The effect of preanaesthetic oral trazodone hydrochloride on the induction dose of propofol: a preliminary retrospective study.

OBJECTIVE: To determine whether the administration of trazodone to dogs 2 hours prior to radiotherapy treatment reduced the dose of propofol required to induce anaesthesia. STUDY DESIGN: Retrospective, crossover, case-matched study. ANIMALS: Records of 30 client-owned dogs. METHODS: Anaesthetic records from all dogs undergoing weekly radiotherapy treatment between January 2020 and December 2020 were retrospectively assessed. All dogs were premedicated with 10 µg kg-1 alfentanil and 12 µg kg-1 atropine intravenously (IV) and anaesthesia was induced with IV propofol. In part 1, the propofol induction dose was compared between anaesthetics when trazodone was administered prior to the anaesthetic (T) versus not (NT). For part 2, control dogs not administered trazodone during the treatment course were case-matched based on bodyweight and tumour location and type. The propofol induction dose was compared between the first (C1) and last (C2) anaesthetic to identify the effects of confounding factors. A Wilcoxon signed-rank test for repeated measurements was performed to identify any significant differences in the propofol induction dose between NT and T in the study dogs and between C1 and C2 in the control dogs. RESULTS: In part 1, 15 study dogs that were administered trazodone prior to at least one anaesthetic were identified. A significant difference in propofol induction dose between groups NT and T was identified [3.3 (2.1-7.4) and 2.0 (1.5-5.0) mg kg-1, respectively; p = 0.003]. In part 2, 15 dogs were case-matched to the study cohort. The dose of propofol administered did not differ between the first and last anaesthetic [2.5 (1.6-6.4) and 2.6 (1.9-8.9) mg kg-1, respectively; p = 0.638]. CONCLUSIONS AND CLINICAL RELEVANCE: Preanaesthetic trazodone administration reduced the induction dose of propofol compared to when it was not administered to dogs following premedication with IV atropine and alfentanil.

Retinoic acid attenuates nuclear factor kappaB mediated induction of NLRP3 inflammasome.

BACKGROUND: Acetylcholine (ACh), a neurotransmitter and a part of the cholinergic system, can modify immune responses. Expression of acetylcholine receptors (AChR) in immune cells, including macrophages, leads to modulation of their function. Inflammasomes are part of the innate immune system and have been linked to a variety of inflammatory diseases. The NLRP3/ASC/caspase-1/IL-1 axis has emerged as a critical signaling pathway in inflammation process initiation. The role of ACh in modulating inflammasomes in macrophages remains relatively under-explored. METHODS: The effect of AChR agonist carbachol on inflammasome expression was investigated using murine and human macrophages. Cell lysates were assessed by western blot for protein analysis. Immunofluorescence studies were used to study the translocation of p65. The experiments were conducted in the presence of NF-ĸB inhibitor, AChR antagonists, and retinoic acid (RA) to study the role of NF-ĸB, ACh receptors, and RA, respectively. RESULTS: We found that carbachol increased the expression of NLRP3 inflammasome (NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18). The treated cells also showed an increase in NF-ĸB activation. The effect of carbachol was diminished by NF-ĸB inhibitor and atropine, a mAChR antagonist. The addition of RA also significantly reduced the effect of carbachol on NLRP3 inflammasomes. CONCLUSIONS: Our current study suggests that carbachol induces NLRP3 inflammasome activation through mAChR and NF-ĸB, and that RA abolishes the inflammatory response. It reveals the potentials of co-administration of RA with cholinergic drugs to prevent inflammatory responses during cholinergic medications.

Cardiac Output Assessments in Anesthetized Children: Dynamic Capnography Versus Esophageal Doppler.

BACKGROUND: The objective of this study was to compare esophageal Doppler cardiac output (COEDM) against the reference method effective pulmonary blood flow cardiac output (COEPBF), for agreement of absolute values and ability to detect change in cardiac output (CO) in pediatric surgical patients. Furthermore, the relationship between these 2 methods and noninvasive blood pressure (NIBP) parameters was evaluated. METHODS: Fifteen children American Society of Anesthesiology (ASA) I and II (median age, 8 months; median weight, 9 kg) scheduled for surgery were investigated in this prospective observational cohort study. Baseline COEPBF/COEDM/NIBP measurements were made at positive end-expiratory pressure (PEEP) 3 cm H2O. PEEP was increased to 10 cm H2O and COEPBF/COEDM/NIBP was recorded after 1 and 3 minutes. PEEP was then lowered to 3 cm H2O, and all measurements were repeated after 3 minutes. Finally, 20-µg kg-1 intravenous atropine was given with the intent to increase CO, and all measurements were recorded again after 5 minutes. Paired recordings of COEDM and COEPBF were examined for agreement and trending ability, and all parameters were analyzed for their responses to the hemodynamic challenges. RESULTS: Bias between COEDM and COEPBF (COEDM - COEPBF) was -17 mL kg-1 min-1 (limits of agreement, -67 to +33 mL kg-1 min-1) with a mean percentage error of 32% (95% confidence interval [CI], 25-37) and a concordance rate of 71% (95% CI, 63-80). The hemodynamic interventions caused by PEEP manipulations resulted in significant decrease in COEPBF absolute numbers (155 mL kg-1 min-1 [95% CI, 151-159] to 127 mL kg-1 min-1 [95% CI, 113-141]) and a corresponding relative decrease of 18% (95% CI, 14-22) 3 minutes after application of PEEP 10. No corresponding decreases were detected by COEDM. Mean arterial pressure showed a relative decrease with 5 (95% CI, 2-8) and 6% (95% CI, 2-10) 1 and 3 minutes after the application of PEEP 10, respectively. Systolic arterial pressure showed a relative decrease of 5% (95% CI, 2-10) 3 minutes after application of PEEP 10. None of the recorded parameters responded to atropine administration except for heart rate that showed a 4% relative increase (95% CI, 1-7, P = .02) 5 minutes after atropine. CONCLUSIONS: COEDM was unable to detect the reduction of CO cause by increased PEEP, whereas COEPBF and to a minimal extent NIBP detected these changes in CO. The ability of COEPBF to react to minor reductions in CO, before noticeable changes in NIBP are seen, suggests that COEPBF may be a potentially useful tool for hemodynamic monitoring in mechanically ventilated children.

Effect of administering dexmedetomidine with or without atropine on cardiac troponin I level in isoflurane-anesthetized dogs.

We aimed to determine whether dexmedetomidine administration with or without atropine increases cardiac troponin I (cTnI) level in healthy dogs. We hypothesized that 10 µg/kg dexmedetomidine + atropine increases the cTnI level, whereas 5 µg/kg dexmedetomidine + atropine does not. Eighteen healthy, pet dogs that underwent an orthopedic surgery or ovariohysterectomy were included in this study. The dogs were randomly assigned to atropine (0.02 mg/kg)-dexmedetomidine (10 µg/kg), saline-dexmedetomidine (10 µg/kg), and atropine (0.02 mg/kg)-dexmedetomidine (5 µg/kg) groups. Each dog was premedicated with atropine or saline intramuscularly (IM). After 10 min, they were IM injected with dexmedetomidine (10 or 5 µg/kg)-morphine (0.5 mg/kg)-midazolam (0.2 mg/kg). Following this, anesthesia was induced after 10 min with propofol and maintained with isoflurane in 100% oxygen. The median plasma cTnI level at 6, 12 and 24 hr after premedication was significantly higher than that at baseline. The cTnI level in the atropine-dexmedetomidine (10 µg/kg) group was significantly higher than that in the saline-dexmedetomidine (10 µg/kg) and atropine-dexmedetomidine (5 µg/kg) groups at 6 and 12 hr after premedication. The cTnI level returned to normal within 72 hr after premedication in all groups. The administration of atropine in combination with 10 µg/kg dexmedetomidine increased the cTnI level, indicating subclinical myocardial damage.

Participation of the Cholinergic System in the Development of Polycystic Ovary Syndrome.

In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.

M1 macrophages-derived exosomes miR-34c-5p regulates interstitial cells of Cajal through targeting SCF.

Slow transit constipation (STC) is a gastrointestinal disorder characterized by abnormal prolonged colonic transit time, which affects the life quality of many people. The decrease number of interstitial cells of Cajal (ICCs) is involved in the pathogenesis of STC. However, the molecular mechanism of loss of ICCs in STC remains unclear, making it difficult to develop new agents for the disease. In this study, we investigated the mechanism of decreasing ICCs in the pathogenesis of STC. We constructed the STC model rats by using atropine and diphenoxylate. A series of methods were used including immunofluorescence and immunochemistry staining, western blot, qRT-PCR, exosomes extraction and exosomes labeling. The results indicate that ICCs decreased in the STC rats accompanied with the macrophages activation. Further studies suggested that macrophages decreased the cell viability of ICCs by secretion exosomes containing miR-34c-5p. miR-34c5p targeted the 3Ꞌ -UTR of stem cell factor(SCF) mRNA and regulated the expression of SCF negatively. In conclusion, we demonstrated a novel regulatory mechanism of ICCs cell viability in STC. We found that exosome miR-34c-5p mediate macrophage-ICCs cross-talk. M1 macrophages derived exosomes miR-34c-5p decreased ICCs cell viability by directly targeting SCF.

The sympathetic/beta-adrenergic pathway mediates irisin regulation of cardiac functions in zebrafish.

Irisin is a 23 kDa myokine encoded in its precursor, fibronectin type III domain containing 5 (FNDC5). The exercise-induced increase in the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) promotes FNDC5 mRNA, followed by the proteolytic cleavage of FNDC5 to release irisin from the skeletal or cardiac muscle into the blood. Irisin is abundantly expressed in skeletal and cardiac muscle and plays an important role in feeding, modulates appetite regulatory peptides, and regulates cardiovascular functions in zebrafish. In order to determine the potential mechanisms of acute irisin effects, in this research, we explored whether adrenergic or muscarinic pathways mediate the cardiovascular effects of irisin. Propranolol (100 ng/g B·W) alone modulated cardiac functions, and when injected in combination with irisin (0.1 ng/g B·W) attenuated the effects of irisin in regulating cardiovascular functions in zebrafish at 15 min post-injection. Atropine (100 ng/g B·W) modulated cardiovascular physiology in the absence of irisin, while it was ineffective in influencing irisin-induced effects on cardiovascular functions in zebrafish. At 1 h post-injection, irisin downregulated PGC-1 alpha mRNA, myostatin-a and myostatin-b mRNA expression in zebrafish heart and skeletal muscle. Propranolol alone had no effect on the expression of these mRNAs in zebrafish and did not alter the irisin-induced changes in expression. At 1 h post-injection, irisin siRNA downregulated PGC-1 alpha, troponin C and troponin T2D mRNA expression, while upregulating myostatin a and b mRNA expression in zebrafish heart and skeletal muscle. Atropine alone had no effects on mRNA expression, and was unable to alter effects on mRNA expression of siRNA. Overall, this research identified a role for the sympathetic/beta-adrenergic pathway in regulating irisin effects on cardiovascular physiology and cardiac gene expression in zebrafish.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 1: attenuation of purinergic bladder smooth muscle contractions.

This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Controls included six sham-operated and three unoperated animals. Detrusor muscle was assessed for contractile responses to potassium chloride (KCl) and electric field stimulation (EFS) before and after purinergic receptor desensitization with α, ß-methylene adenosine triphosphate (α,ß-mATP), muscarinic receptor antagonism with atropine, or sodium channel blockade with tetrodotoxin. Atropine inhibition of EFS-induced contractions increased in decentralized and reinnervated animals compared with controls. Maximal contractile responses to α,ß-mATP did not differ between groups. In strips from decentralized and reinnervated animals, the contractile response to EFS was enhanced at lower frequencies compared with normal controls. The observation of increased blockade of nerve-evoked contractions by muscarinic antagonist with no change in responsiveness to purinergic agonist suggests either decreased ATP release or increased ecto-ATPase activity in detrusor muscle as a consequence of the long-term decentralization. The reduction in the frequency required to produce maximum contraction following decentralization may be due to enhanced nerve sensitivity to EFS or a change in the effectiveness of the neurotransmission.

Role of Muscarinic Receptors in Hypoalgesia Induced by Crocin in Neuropathic Pain Rats.

OBJECTIVE: Crocin as an important constituent of saffron has antineuropathic pain properties; however, the exact mechanism of this effect is not known. The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors. MATERIALS AND METHODS: In the present project, 36 male Wistar rats (200 ± 20 g) were used. Animals randomly divided into six groups (sham, neuropathy, neuropathy + crocin, neuropathy + atropine 0.5 mg/kg, neuropathy + atropine 1 mg/kg, and neuropathy + atropine 1 mg/kg + crocin). Neuropathy was induced by the chronic constriction injury (CCI) method on the sciatic nerve. Crocin and atropine was administered intraperitoneally during 14 days following the 14th day after surgery. Pain response was detected every three days, two hours after each injection and 3 days following last injection. Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device, respectively. RESULTS: CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus (P < 0.01 and P < 0.05, respectively). Crocin therapy significantly reduced mechanical allodynia and thermal hyperalgesia induced by CCI (P < 0.05). Atropine pretreatment significantly blocked the hypoalgesic effect of crocin (P < 0.05 in mechanical allodynia and P < 0.01 in thermal hyperalgesia). Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery. CONCLUSION: Crocin significantly decreased CCI-induced neuropathic pain. The hypoalgesic effect of crocin was blocked by atropine pretreatment, which indicates an important role for muscarinic receptors in the effect of crocin.