Influence of Anticholinesterase Drugs on Activity and Properties of Na+,K+-ATPase in Rat Erythrocytes under Stress Caused by Intense Physical Exercise.

We studied the effect of intramuscular injection of physostigmine and neostigmine on Na+,K+-ATPase activity in erythrocytes of rats subjected to intense physical exercise. Both anticholinesterase drugs had a significant effect on the development of the stress response, which was expressed in a decrease in the manifestation of its individual components such as the concentration of ascorbic acid in the adrenal glands, stress-related erythrocyte polycythemia, and LPO indicators. Anticholinesterase drugs reverse the stress-induced decrease in Na+,K+-ATPase activity, as well as changes in its magnesium-dependent properties. There were no changes in the activity of the studied enzyme in the erythrocyte ghosts. We associate the observed differences with the correction of the functions of the cholinergic components of the hypothalamic-pituitary-adrenal axis leading to the development of a hypoergic type stress reaction.

Effect of sugammadex with neostigmine on postoperative bowel function and on recovery of neuromuscular functions: A randomized controlled trial.

BACKGROUND: Early recovery of neuromuscular and bowel function after abdominal surgery are important clinical indicators of postoperative recovery. This study aimed to investigate the effects of sugammadex, and neostigmine added to sugammadex, on postoperative bowel function and recovery from neuromuscular blocking agents. METHODS: Ninety gynecological surgery patients, aged 18 to 65 years, with American Society of Anesthesiologists of 1 to 2 were randomly assigned to 3 groups: sugammadex 2 mg/kg (Group S), sugammadex 1 m/kg with neostigmine 20 µg/kg + atropine 10 µg/kg (Group S1N), and sugammadex 1.5 mg/kg with neostigmine 20 µg/kg + atropine 10 µg/kg (Group S2N), for reversal at the end of surgery during moderate block (train-of-four [TOF] count 1-2). Propofol, remifentanil, rocuronium, and sevoflurane were used for general anesthesia, and neuromuscular function was assessed using kinemyography. The primary outcomes assessed the effects of sugammadex alone and in combination with neostigmine on the time to first flatus. The secondary outcomes included time to first defecation and recovery time; defined as the administration of reversal agent to TOF ratio 90%. RESULTS: Data from 90 female patients who underwent abdominal gynecological surgery were analyzed. No significant differences were found between the groups in term of the time to first flatus, defecation, or postoperative nausea and vomiting after surgery. However, significant differences were observed in the time to reach a TOF ratio 90% (P < .001) and extubation time (P = .003). CONCLUSION: The addition of neostigmine to sugammadex did not affect bowel function recovery. However, combining 20 µg/kg neostigmine with 1.5 mg/kg sugammadex or 2 mg/kg sugammadex alone antagonized moderate-depth nondepolarizing neuromuscular blockade with similar efficacy.

Navigating Anesthesia: Muscle Relaxants and Reversal Agents in Patients with Renal Impairment.

This comprehensive review explores the interaction between neuromuscular blocking agents, reversal agents, and renal function, focusing on various drugs commonly used in anesthesia and their effects on kidney health. Succinylcholine, commonly used for anesthesia induction, can trigger elevated potassium levels in patients with specific medical conditions, leading to serious cardiac complications. While studies suggest the use of succinylcholine in patients with renal failure is safe, cases of postoperative hyperkalemia warrant further investigation. Some agents, such as atracurium and mivacurium, are minimally affected by impaired kidney function, whereas others, such as cisatracurium and rocuronium, can have altered clearance, necessitating dose adjustments in patients with renal failure. The reversal agents neostigmine and sugammadex affect renal markers, while cystatin C levels remain relatively stable with sugammadex use, indicating its milder impact on glomerular function, compared with neostigmine. Notably, the combination of rocuronium and sugammadex in rat studies shows potential nephrotoxic effects, cautioning against the simultaneous use of these agents. In conclusion, understanding the interplay between neuromuscular blocking agents and renal function is crucial for optimizing patient care during anesthesia. While some agents can be used safely in patients with renal failure, others can require careful dosing and monitoring. Further research is needed to comprehensively assess the long-term impact of these agents on kidney health, especially in high-risk patient populations. This article aims to review the use of muscle relaxants and reversal for anesthesia in patients with impaired renal function.

Effect of coadministration of 10 mg/kg calcium chloride and neostigmine on extubation time: A randomized controlled trial.

INTRODUCTION AND OBJECTIVES: Some studies investigating the effect of calcium on neostigmine-induced recovery of neuromuscular blockade have shown that this combination promotes neuromuscular recovery, but does not significantly affect the incidence of postoperative residual curarization and time to extubation. This study aimed to evaluate the effects of 10 mg/kg calcium chloride co-administered with neostigmine on early recovery and time to extubation. PATIENTS AND METHODS: This prospective, randomized, double-blinded, placebo-controlled study included 88 ASA I-II patients aged between 18 and 65 years who were scheduled for elective surgery lasting at least 1 h under general anaesthesia in which 10 mg/kg of calcium chloride or the same volume of normal saline was co-administered with 5 µg/kg of neostigmine at the end of surgery. Time to extubation (time from neostigmine administration to extubation), time from neostigmine administration to TOF ratio (TOFr) 0.9 (neuromuscular recovery), and the incidence of residual neuromuscular blockade (RNMB) and other adverse effects were recorded. RESULTS: Median (Q1, Q3) extubation time was significantly shorter in the calcium group vs. the placebo group (6.5 min [5.52-7.43] vs. 9.78 min [8.35-11]), P < .001. Median neuromuscular recovery time in the calcium group was 5 min vs. 7.1 min in the placebo group, P < .001. Patients in the calcium group had significantly higher TOFr and lower incidence of RNMB at 5 and 10 min vs. the placebo group, and no significant side effects. CONCLUSION: Calcium chloride at a dose of 10 mg/kg co-administered with neostigmine promotes early neuromuscular recovery and reduces time to extubation by about 32%.

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.

Central cholinergic transmission affects the compulsive-like behavior of mice in marble-burying test.

The presence of the cholinergic system in the brain areas implicated in the precipitation of obsessive-compulsive behavior (OCB) has been reported but the exact role of the central cholinergic system therein is still unexplored. Therefore, the current study assessed the effect of cholinergic analogs on central administration on the marble-burying behavior (MBB) of mice, a behavior correlated with OCB. The result reveals that the enhancement of central cholinergic transmission in mice achieved by intracerebroventricular (i.c.v.) injection of acetylcholine (0.01 µg) (Subeffective: 0.1 and 0.5 µg), cholinesterase inhibitor, neostigmine (0.1, 0.3, 0.5 µg/mouse) and neuronal nicotinic acetylcholine receptor agonist, nicotine (0.1, 2 µg/mouse) significantly attenuated the number of marbles buried by mice in MBB test without affecting basal locomotor activity. Similarly, central injection of mAChR antagonist, atropine (0.1, 0.5, 5 µg/mouse), nAChR antagonist, mecamylamine (0.1, 0.5, 3 µg/mouse) per se also reduced the MBB in mice, indicative of anti-OCB like effect of all the tested cholinergic mAChR or nAChR agonist and antagonist. Surprisingly, i.c.v. injection of acetylcholine (0.01 µg), and neostigmine (0.1 µg) failed to elicit an anti-OCB-like effect in mice pre-treated (i.c.v.) with atropine (0.1 µg), or mecamylamine (0.1 µg). Thus, the findings of the present investigationdelineate the role of central cholinergic transmission in the compulsive-like behavior of mice probably via mAChR or nAChR stimulation.

Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial.

Magnesium enhances the effects of neuromuscular blocking agents. However, there is a paucity of evidence demonstrating possible effects of magnesium on neostigmine-induced recovery from neuromuscular blockade with rocuronium. This study compared the profiles of recovery from neuromuscular blockade between groups treated with magnesium (Group M) and placebo controls (Group C). Sixty-four patients were randomly allocated to Group M or Group C. Patients in Group M received a loading dose of 50 mg/kg magnesium and continuous infusion of 15 mg/kg/hr. Patients in Group C received a comparable amount of saline. Rocuronium at 0.6 mg/kg was used for tracheal intubation and 0.1 mg/kg of rocuronium was additionally administered to maintain train-of-four (TOF) status of 2-3 during surgery. At the end of surgery, neostigmine (50 µg/kg) plus glycopyrrolate (10 µg/kg) were administered, and the recovery time for TOF ratios of 0.7, 0.8, and 0.9 was measured. The primary outcome was the time from neostigmine administration to recovery with a TOF ratio of 0.9. In addition, rocuronium onset time (time from administration of rocuronium to 95% suppression of the first TOF twitch response), additional requirements for rocuronium and spontaneous recovery period (the time from administration of rocuronium to reappearance of the first TOF twitch response) were also measured. Neostigmine-induced recovery time was comparable between Group M and Group C (10.6 ± 4.3 vs. 9.1 ± 5.0 min, respectively, p = 0.22). The rocuronium onset time was shorter in Group M, and the spontaneous recovery period was longer in Group M. The amount of additional rocuronium administered was 27% lower in Group M, but this difference was not significant. Magnesium was not shown to prolong neostigmine-induced recovery time from neuromuscular blockade with rocuronium, however, it enhanced the clinical effects of rocuronium.

Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study.

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Generalised neuromuscular blockade after intraurethral administration of atracurium besilate in a male cat with urethral obstruction.

A 4-year-old, entire, male, domestic long-haired cat was presented with an acute history of stranguria and dysuria and diagnosed with urolithiasis causing urethral obstruction. The patient was induced to general anaesthesia and several unsuccessful attempts to flush the uroliths retrogradely towards the bladder were made. An intraurethral administration of the neuromuscular blocking agent atracurium was performed as it has been reported to facilitate urethral catheterisation without any side effects. Respiratory arrest developed after 15 minutes from atracurium administration, which was promptly recognized and treated with mechanical ventilation. The absence of muscle contraction in response to a nerve stimulation confirmed a generalised muscle blockade. Approximately 35 minutes after, a muscle response to nerve stimulation appeared. Neostigmine combined with glycopyrrolate was administered resulting in complete recovery from neuromuscular blockade. In conclusion, the use of intraurethral atracurium can result in systemic absorption of the drug with subsequent generalised neuromuscular blockade.

Postoperative pulmonary complications after sugammadex reversal of neuromuscular blockade: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Sugammadex has been reported to lower the incidence of postoperative residual neuromuscular blockade. Despite the advantages, until recently the effects of sugammadex on postoperative pulmonary complications (PPCs) were controversial. We conducted a systematic review and meta-analysis to determine whether reversal with sugammadex was associated with a lower risk of PPCs compared with neostigmine. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to May 2022. Randomized controlled trials (RCTs) and observational studies comparing PPCs in patients receiving sugammadex or neostigmine as reversal agent at the end of surgery were included. The primary outcomes focused on PPCs including desaturation, pneumonia, atelectasis, noninvasive ventilation (NIV) and reintubation. Trial sequential analysis was performed on the primary outcomes to confirm whether firm evidence was reached. RESULTS: Meta-analysis of included studies showed that the rate of desaturation (43.2% vs 45.0%, RR = 0.82; 95% CI 0.63 to 1.05; p = 0.11) were comparable between the two groups. When looking at other primary outcomes, significantly lower risk of pneumonia (1.37% vs 2.45%, RR = 0.65; 95% CI 0.49 to 0.85; p = 0.002), atelectasis (24.6% vs 30.4%, RR = 0.64; 95% CI 0.42 to 0.98; p = 0.04), NIV (1.37% vs 2.33%, RR = 0.65; 95% CI 0.43 to 0.98; p = 0.04) and reintubation (0.99% vs 1.65%, RR = 0.62; 95% CI 0.43 to 0.91; p = 0.01) in the sugammadex group were detected compared with the neostigmine group. CONCLUSIONS: We concluded that sugammadex is more effective at reducing the incidence of PPCs including pneumonia, atelectasis, NIV and reintubation compared with neostigmine. Further evidence, preferably from RCTs, is required to confirm these findings.

Subclinical involvement of eye movements detected by video-based eye tracking in myasthenia gravis.

BACKGRO UND: Ocular abnormalities in myasthenia gravis (MG) are characterized by severely limited movements and rapid saccades. Data about eye motility of MG patients whose ocular movements are apparently normal are lacking. Our study assessed the eye movement parameters in MG patients without clinical eye motility dysfunctions and investigated the effects of neostigmine administration on the eye motility in these patients. MATERIALS: In this longitudinal study, we screened all patients diagnosed with MG referring to the Neurologic Clinic of the University of Catania between October 1, 2019, and June 30, 2021. Ten age- and sex-matched healthy controls were enrolled. Patients underwent eye movement recording using the EyeLink1000 Plus® eye tracker at baseline and after 90 min from the intramuscular administration of neostigmine (0.5 mg). RESULTS: A total of 14 MG patients with no clinical signs of ocular motor dysfunction (64.3% men, with a mean age of 50.4 ± 14.4 years) were enrolled. At baseline, saccades in MG patients showed slower velocities and longer latencies compared to controls. Moreover, the fatigue test induced a reduction in saccadic velocity and an increase in latencies. After neostigmine administration, the ocular motility analysis showed shorter saccadic latencies and a significant improvement of velocities. CONCLUSIONS: Eye motility is impaired even in MG patients with no clinical evidence of ocular movement disturbance. Video-based eye tracking may detect subclinical involvement of eye movements in patients with MG.

Effects of Reversal Technique for Neuromuscular Paralysis on Time to Recovery of Bowel Function after Craniotomy.

BACKGROUND: Non-depolarizing neuromuscular blockade can be reversed with neostigmine/glycopyrrolate or sugammadex. We test the hypothesis that sugammadex is associated with earlier postoperative recovery of bowel function (first bowel movement, BM). METHODS: In adult patients undergoing craniotomy from 2016 to 2019, we identified time of first postoperative BM after receiving neostigmine/glycopyrrolate or sugammadex to reverse neuromuscular blockade. Logistic and proportional hazard regression, with and without inverse probability of treatment weighting (IPTW), were used to assess whether sugammadex is associated with earlier recovery of bowel function. RESULTS: Seven hundred and thirty-one patients underwent craniotomy, 323 (44.2%) received neostigmine/glycopyrrolate, and 408 (55.8%) sugammadex. From logistic regression analysis, the proportion of patients having a BM within the first 24 and 48 hours was higher in sugammadex group (unadjusted OR [95% CI]) 1.79 [1.16 to 2.77] P = .009; and 1.45 [1.08 to 1.94] P = .014; IPTW adjusted OR [95% CI]) 1.58 [.95, 2.61] P = .078; and 1.38 [.95 to 2.02] P = .095 for 24 and 48 h, respectively). From proportional hazards regression, sugammadex was associated with improved bowel function recovery (unadjusted hazard ratio (HR) [95% CI] 1.35 [1.08, 1.68], P = .008; IPTW adjusted HR 1.29 [.97 to 1.71], P = .076). CONCLUSION: Patients undergoing craniotomy who had neuromuscular blockade reversed with sugammadex may have earlier recovered bowel function compared to patients reversed with neostigmine/glycopyrrolate.

Case Report: Successful Reversal of Residual Block with Sugammadex in a Patient Not Known to Have Myasthenia Gravis.

BACKGROUND Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. CASE REPORT A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-of-four [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. CONCLUSIONS When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

Optimizing Reversal of Neuromuscular Block in Older Adults: Sugammadex or Neostigmine.

Residual neuromuscular paralysis, the presence of clinically significant weakness after administration of pharmacologic neuromuscular blockade reversal, is associated with postoperative pulmonary complications and is more common in older patients. In contemporary anesthesia practice, reversal of neuromuscular blockade is accomplished with neostigmine or sugammadex. Neostigmine, an acetylcholinesterase inhibitor, increases the concentration of acetylcholine at the neuromuscular junction, providing competitive antagonism of neuromuscular blocking drug and facilitating muscle contraction. Sugammadex, a modified gamma-cyclodextrin, antagonizes neuromuscular blockade by encapsulating rocuronium and vecuronium in a one-to-one ratio for renal clearance, a pharmacokinetic property that led to the recommendation that sugammadex not be administered to those with end-stage renal disease. While data are limited, reports suggest sugammadex is efficacious and well tolerated in individuals with reduced renal function. Sugammadex provides a more rapid and complete reversal of neuromuscular blockade than neostigmine. There is also accumulating evidence that sugammadex may provide a protective effect against the development of postoperative pulmonary complications, nausea, and vomiting, and that it may have beneficial effects on the rate of bowel and bladder recovery after surgery. Accordingly, sugammadex administration is beneficial for most older patients undergoing surgery.

The interaction between hippocampal cholinergic and nitrergic neurotransmission coordinates NMDA-dependent behavior and autonomic changes induced by contextual fear retrieval.

RATIONALE: Re-exposing an animal to an environment previously paired with an aversive stimulus evokes large alterations in behavioral and cardiovascular parameters. Dorsal hippocampus (dHC) receives important cholinergic inputs from the basal forebrain, and respective acetylcholine (ACh) levels are described to influence defensive behavior. Activation of muscarinic M1 and M3 receptors facilitates autonomic and behavioral responses along threats. Evidence show activation of cholinergic receptors promoting formation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in dHC. Altogether, the action of ACh and NO on conditioned responses appears to converge within dHC. OBJECTIVES: As answer about how ACh and NO interact to modulate defensive responses has so far been barely addressed, we aimed to shed additional light on this topic. METHODS: Male Wistar rats had guide cannula implanted into the dHC before being submitted to the contextual fear conditioning (3footshocks/085 mA/2 s). A catheter was implanted in the femoral artery the next day for cardiovascular recordings. Drugs were delivered into dHC 10 min before contextual re-exposure, which occurred 48 h after the conditioning procedure. RESULTS: Neostigmine (Neo) amplified the retrieval of conditioned responses. Neo effects (1 nmol) were prevented by the prior infusion of a M1-M3 antagonist (fumarate), a neuronal nitric oxide synthase inhibitor (NPLA), a NO scavenger (cPTIO), a guanylyl cyclase inhibitor (ODQ), and a NMDA antagonist (AP-7). Pretreatment with a selective M1 antagonist (pirenzepine) only prevented the increase in autonomic responses induced by Neo. CONCLUSION: The results show that modulation in the retrieval of contextual fear responses involves coordination of the dHC M1-M3/NO/cGMP/NMDA pathway.

Effects of sugammadex and neostigmine on mucociliary clearance in general anesthesia.

OBJECTIVE: The aim of this study was to evaluate the effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance. PATIENTS AND METHODS: This prospective, randomized and double-blind study was performed on 60 non-smokers with ASA I-III underwent inguinal hernia repair under general anesthesia. Mucociliary clearance was assessed by nasal saccharine transit time (STT). After the preoperative STT measurement, the patients were taken to the operating room, and divided into two equal groups as group 1 and 2 (n= 30 for each group). Midazolam, propofol, and rocuronium were used in all patients. Anesthesia was maintained by sevoflurane at a flow rate of 6 lt/min (50% O2 - 50% N2O) with a minimum alveolar concentration of 1.3-1.5. After the surgical procedure, atropine-neostigmine (20 mcg/kg - 50 mcg/kg) and sugammadex (2 mg/kg) were administered to group 1 and group 2, respectively, and then the patients were extubated. The postoperative STT was measured in postoperative period. RESULTS: The mean age of the patients was 53 (±16) years, and 56 (93%) of them were male. There were no differences between the groups in terms of age, gender, height, weight, ASA score, and duration of anesthesia, duration of surgery, postoperative period, preoperative STT, and postoperative STT. However, when each group was evaluated separately, there was a statistically significant increase in the postoperative STT compared to the preoperative STT in both groups (p=0.005 for group 1, p<0.001 for group 2). CONCLUSIONS: The effects of sugammadex and neostigmine used in general anesthesia on postoperative mucociliary clearance are similar, and postoperative mucociliary clearance is delayed.

Fentanyl and neostigmine delivered to mouse prefrontal cortex differentially alter breathing.

Opioids impair many functions modulated by the prefrontal cortex (PFC), including wakefulness, cognition, and breathing. In contrast, cholinergic activity in the PFC increases wakefulness. This study tested the hypothesis that microinjecting the opioid fentanyl and the acetylcholinesterase inhibitor neostigmine into the PFC of awake C57BL/6J male mice (n = 27) alters breathing. The lateral and medial PFC were unilaterally microinjected with saline (control) and fentanyl. The medial PFC received additional microinjections of neostigmine. The results show that fentanyl caused site-specific changes in breathing. Fentanyl delivered to the lateral PFC significantly decreased minute ventilation variability, whereas fentanyl delivered to the medial PFC significantly increased tidal volume and duty cycle. Neostigmine microinjected into the medial PFC significantly increased respiratory rate, tidal volume, and minute ventilation. A final series of experiments revealed that decreased minute ventilation caused by systemic fentanyl administration was mitigated by PFC microinjection of neostigmine.