Showing papers on "Atropine published in 2008"

RGS4 Regulates Parasympathetic Signaling and Heart Rate Control in the Sinoatrial Node

Abstract: Heart rate is controlled by the opposing activities of sympathetic and parasympathetic inputs to pacemaker myocytes in the sinoatrial node (SAN). Parasympathetic activity on nodal myocytes is mediated by acetylcholine-dependent stimulation of M(2) muscarinic receptors and activation of Galpha(i/o) signaling. Although regulators of G protein signaling (RGS) proteins are potent inhibitors of Galpha(i/o) signaling in many tissues, the RGS protein(s) that regulate parasympathetic tone in the SAN are unknown. Our results demonstrate that RGS4 mRNA levels are higher in the SAN compared to right atrium. Conscious freely moving RGS4-null mice showed increased bradycardic responses to parasympathetic agonists compared to wild-type animals. Moreover, anesthetized RGS4-null mice had lower baseline heart rates and greater heart rate increases following atropine administration. Retrograde-perfused hearts from RGS4-null mice showed enhanced negative chronotropic responses to carbachol, whereas SAN myocytes showed greater sensitivity to carbachol-mediated reduction in the action potential firing rate. Finally, RGS4-null SAN cells showed decreased levels of G protein-coupled inward rectifying potassium (GIRK) channel desensitization and altered modulation of acetylcholine-sensitive potassium current (I(KACh)) kinetics following carbachol stimulation. Taken together, our studies establish that RGS4 plays an important role in regulating sinus rhythm by inhibiting parasympathetic signaling and I(KACh) activity.

Activation of Muscarinic Receptors in Rat Bladder Sensory Pathways Alters Reflex Bladder Activity

Abstract: Antimuscarinic drugs affect bladder sensory symptoms such as urgency and frequency, presumably by acting on muscarinic acetylcholine receptors (mAChRs) located in bladder sensory pathways including primary afferent nerves and urothelium. However, the expression and the function of these receptors are not well understood. This study investigated the role of mAChRs in bladder sensory pathways in vivo in urethane anesthetized rats. Intravesical administration of the mAChR agonist oxotremorine methiodide (OxoM) elicited concentration-dependent excitatory and inhibitory effects on the frequency of voiding. These effects were blocked by intravesical administration of the mAChR antagonist atropine methyl nitrate (5 microM) and were absent in rats pretreated with capsaicin to desensitize C-fiber afferent nerves. Low concentrations of OxoM (5 microM) decreased voiding frequency by approximately 30%, an effect blunted by inhibiting nitric oxide (NO) synthesis with L-NAME (N(omega)-nitro-L-arginine methyl ester hydrochloride; 5 mg/kg; i.v.). High concentrations of OxoM (40 microM) increased voiding frequency by approximately 45%, an effect blunted by blocking purinergic receptors with PPADS (0.1-1 mM; intravesically). mAChR agonists stimulated release of ATP from cultured urothelial cells. Intravenous administration of OxoM (0.01-5 microg/kg) did not mimic the intravesical effects on voiding frequency. These results suggest that activation of mAChRs located near the luminal surface of the bladder affects voiding functions via mechanisms involving ATP and NO release presumably from the urothelium, that in turn could act on bladder C-fiber afferent nerves to alter their firing properties. These findings suggest that the urothelial-afferent nerve interactions can influence reflex voiding function.

Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channels.

Abstract: This study describes the spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory and urinary bladder relaxant properties of Hyoscyamus niger to rationalize some of its medicinal uses. The crude extract of H. niger seeds (Hn.Cr) caused a complete concentration-dependent relaxation of spontaneous contractions of rabbit jejunum, similar to that caused by verapamil, whereas atropine produced partial inhibition. Hn.Cr inhibited contractions induced by carbachol (1 microM) and K(+) (80 mM) in a pattern similar to that of dicyclomine, but different from verapamil and atropine. Hn.Cr shifted the Ca(2+) concentration-response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca(2+) channel-blocking mechanism in addition to an anticholinergic effect. In the guinea-pig ileum, Hn.Cr produced a rightward parallel shift of the acetylcholine curves, followed by a non-parallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine. Hn.Cr exhibited antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation in mice. In guinea-pig trachea and rabbit urinary bladder tissues, Hn.Cr caused relaxation of carbachol (1 microM) and K(+) (80 mM) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca(2+) antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect. A constituent, beta-sitosterol exhibited Ca(2+) channel-blocking action. These results suggest that the antispasmodic effect of H. niger is mediated through a combination of anticholinergic and Ca(2+) antagonist mechanisms. The relaxant effects of Hn.Cr occur at much lower concentrations in the trachea and bladder. This study offers explanations for the medicinal use of H. niger in treating gastrointestinal and respiratory disorders and bladder hyperactivity.

Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies.

Abstract: The phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals, and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma cells. We also show that fluoxetine (20 mg/kg/day × 7 days), as well as a combination of sildenafil (10 mg/kg/day × 7 days) plus the antimuscarinic atropine (1 mg/kg/day × 7 days) demonstrates significant, comparable antidepressant-like effects in the rat forced swim test (FST) and also reduces cortical β-adrenergic receptor (β-AR) density, while sildenafil or atropine alone did not. Importantly, sildenafil did not modify fluoxetine’s response. Sildenafil thus demonstrates antidepressant-like effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in the neurobiology of depression.

Atropine and glycopyrronium premedication. A comparison of the effects on cardiac rate and rhythm during induction of anaesthesia.

Abstract: The effect of premedication with the cholinergic blocking drugs, atropine and glycopyrronium, was investigated in two groups, each of twenty patients, with regard to their effects on cardiac rate and rhythm during induction of anaesthesia and tracheal intubation. Another similar group of twenty patients was given no anticholinergic premedication. The incidence of dysrhythmias was 35% in the atropine group and 10% in the glycopyrronium group but there were no dysrhythmias in patients given no anticholinergic drug. The average rises in arterial pressure were similar in all three groups. Atropine administration led to a greater initial rise in heart rate before the induction of anaesthesia, although the average heart rates were similar in the three groups at the time of intubation and cuff inflation. The routine use of anticholinergic premedication seems to be unnecessary since the antisialogogue effect does not make any difference to the course of anaesthesia. However, if the antisialogogue action is important, glycopyrronium offers an advantage over atropine.

The ability of atropine to prevent and reverse the negative chronotropic effect of fingolimod in healthy subjects

Abstract: WHAT IS KNOWN ABOUT THIS SUBJECT • Clinical pharmacology and clinical therapeutic studies of fingolimod demonstrate that heart rate after the initial dose decreases by about 10–20% while normal circadian rhythm is preserved. With continued daily dosing, heart rate returns to normal over the next 2 weeks. • This negative chronotropic effect is consistent with the binding of fingolimod-phosphate to the sphingosine-1-phosphate receptor on atrial myocytes. WHAT THIS STUDY ADDS • The present clinical pharmacology study demonstrates that atropine administered at usual therapeutic doses can prevent the decrease in heart rate when given concomitantly with fingolimod and can counteract the decrease in heart rate when give at the time of the typical heart rate nadir, 4 h after the fingolimod dose. • Although therapeutic intervention is rarely needed for reduced heart rate in patients receiving fingolimod, atropine is an option, should this be desired. AIMS The authors determined whether intravenous atropine can prevent or counteract the negative chronotropic effect of the immunomodulator fingolimod. METHODS In this randomized, placebo-controlled, two-period, crossover study, 12 healthy subjects received 5 mg fingolimod orally concurrently with intravenous atropine (titrated to a heart rate of 110–120 beats min−1) or intravenous placebo. A second group of 12 subjects received atropine/placebo 4 h after the fingolimod dose. Continuous telemetry measurements were made for 24 h after each fingolimod dose. RESULTS Fingolimod administration alone yielded a heart rate nadir of 51 ± 5 beats min−1 at a median 4 h postdose with heart rate remaining depressed at 51–64 beats min−1 over the rest of the day. Concurrent administration of fingolimod and atropine yielded a nadir of 66 ± 6 beats min−1 resulting in an atropine : placebo ratio (90% confidence interval) of 1.30 (1.22, 1.36). When atropine was administered at the time of the nadir, it was able to reverse the negative chronotropic effect of fingolimod from a heart rate of 56 ± 9 beats min−1 (placebo) to 64 ± 8 beats min−1 (atropine) resulting in an atropine : placebo ratio of 1.15 (1.04, 1.26). Atropine had no influence on the pharmacokinetics of fingolimod. CONCLUSIONS Atropine administered concurrently with fingolimod prevented the heart rate nadir that typically occurs 4 h postdose. Atropine administered at the time of the heart rate nadir was able to reverse the negative chronotropic effect of fingolimod.

Neuroprotection of muscarinic receptor agonist pilocarpine against glutamate-induced apoptosis in retinal neurons.

Abstract: Neuroprotection offers potential as an alternative therapy for glaucoma Pilocarpine, as a typical muscarinic receptor agonist, remains among the major intraocular pressure lowering drugs for the conventional treatment of glaucoma However, whether pilocarpine also possesses neuroprotection against glutamate cytotoxicity in retinal neurons is still unknown In rat primary retinal cultures, identification of neuron, cell viability, apoptosis, intracellular Ca(2+) concentration, mitochondrial membrane potential, gene expression were studied by immunofluorescence, MTT, High Content Scanning, confocal microscopy, reverse-transcription PCR, and western blot analysis, respectively Pretreatment of pilocarpine could prevent glutamate-induced neuron death, which was blocked by the non-selective antagonist atropine and the M1-selective muscarinic receptor antagonist pirenzepine The antiapoptotic effect of pilocarpine was associated with maintaining calcium homeostasis, recovering mitochondrial membrane potential, and regulating the expression of Bcl-2 and Caspase-3 These studies demonstrated that pilocarpine had effective protection against glutamate-induced neuronal apoptosis through M1 muscarinic receptor The results may provide an insight into the new mechanism of glaucoma therapy that pilocarpine may potentially act as a retinal neuroprotectant

Effects of Fitness and Age on the Response to Vagotonic Atropine

Abstract: Previous work indicates compromised cardiac vagal control plays a prominent role in reducing arterial baroreflex gain with age, however older fit individuals display cardiovagal baroreflex responses similar to young individuals. The purpose of this study was to test the hypothesis that chronic aerobic exercise mitigates against age-related declines in cardiac parasympathetic receptor function. In forty-four young and old (fit and unfit) individuals, we used the parasympathomimetic responses to low doses of atropine to probe cardiac cholinergic receptor responses. Data were collected before and after eight doses of atropine sulfate from 0.4 to 7.2 microg/kg. Chronotropic responses were assessed from average RR intervals and heart rate variabilities were derived in time and frequency domains. All subjects exhibited bradycardia with at least one dose of atropine and peak bradycardia occurred at a similar dose in each group. However, changes in heart rate variability did not consistently track the chronotropic responses within subjects (r-square from 0.90 down to 0). As expected, basal RR interval was longer in the fit groups and was unaffected by age. However, the degree of RR interval lengthening with parasympathomimetic atropine was unaffected by physical fitness and was significantly less in all older subjects. These data indicate there are certain prepotent age-related declines in the cardiac parasympathetic system that cannot be prevented by regular physical activity.

Atropine treatment modifies LPS-induced inflammatory response and increases survival.

Abstract: To explore the effect that Atropine, a competitive antagonist for the muscarinic acetylcholine receptor (mAChR), has on the response to LPS. Eight-week-old, male, B6 mice. Mice were treated with Atropine prior to, or after LPS challenge. Survival was monitored and analyzed via Kaplan-Meier analysis using the log-rank test. The effects of atropine on the inflammatory response (TNF-α, IL-6 and IL-10) were monitored at various time intervals following LPS injection in mice that were treated and not treated with atropine. Atropine administration prior to LPS induction of the inflammatory response resulted in reduced TNF-α and elevated IL-10 plasma levels without affecting the production of IL-6. This reduction in TNF-α levels was independent of the increase in IL-10 production. Atropine pretreatment improved the rate of survival from endotoxic shock in mice. The improved survival of mice after endotoxic shock could still be observed when atropine was administered several hours after LPS injection. The administration of atropine after injury may have a beneficial clinical effect.

Contribution of the M3 muscarinic receptors to the vasodilator response to acetylcholine in the human forearm vascular bed.

Abstract: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Available evidence suggests that the M3 receptor on endothelial cells is responsible for acetylcholine (Ach)-dependent vasodilatation. • Data from human studies only provide indirect evidence for this, and results are more difficult to interpret. WHAT THIS STUDY ADDS • This study used the new M3 receptor antagonist darifenacin as a pharmacological ‘tool’ to investigate the role of M3 receptor in the human forearm circulation. • It provides evidence for a major role for the M3 receptors in ACh-dependent vasodilatation in the forearm vascular bed. AIMS Acetylcholine (ACh) is a muscarinic agonist that causes receptor-mediated, endothelium-dependent vasodilatation in the forearm vasculature. Previous indirect evidence suggests this effect may be mediated by muscarinic M3 receptors. Darifenacin is a recently developed antimuscarinic drug with greater M3 selectivity, and our main objective was to investigate whether darifenacin affects dose-dependent vasodilatation to ACh in the forearm circulation. METHODS Healthy subjects were enrolled in two studies designed to assess the effects of atropine and darifenacin on the forearm blood flow (FBF) response to ACh. RESULTS In both studies ACh caused similar dose-dependent vasoditation in the forearm vasculature. In study I (5 subjects), the FBF response to ACh was largely attenuated by pretreatment with the nonselective muscarinic antagonist atropine. In study II (10 subjects), oral administration of darifenacin 15 mg for 1 week significantly reduced the FBF dose-dependent response to ACh 20 µg min−1 {mean difference from placebo 5.8 [95% confidence interval (CI) 3.1, 8.7] ml min−1 per 100 ml of forearm volume, P < 0.001} and to ACh 60 µg min−1[mean difference from placebo 5.9 (95% CI 3.1, 8.7) ml min−1 per 100 ml of forearm volume, P < 0.001]. After darifenacin, the AUC of change in FBF from baseline was reduced by almost 50% compared with placebo. CONCLUSIONS These results suggest that, in the forearm vasculature, muscarinic M3 receptors play a major role in ACh-induced endothelium-mediated vasodilatation.

Consecutive administration of atropine and isoproterenol for the evaluation of asymptomatic sinus bradycardia.

Abstract: Aims Sinus node function is commonly evaluated by the atropine test. The isoproterenol test is less used. The aim of this study was to evaluate chronotropic reserve in patients with asymptomatic sinus bradycardia using the combined administration of atropine and isoproterenol. Methods and results A total of 100 patients were studied, 18–70 years old, with permanent, asymptomatic, sinus bradycardia and no detectable cardiac disease. The standard administration protocols for atropine and isoproterenol were used and successive heart rate recorded. Patients were stratified into three groups: Group A (control), showing normal response to atropine and isoproterenol; Group B, demonstrating abnormal response to atropine; Group C, with abnormal response to atropine and isoproterenol. No statistically significant difference was observed between Groups A and B (P ¼ 0.11), whereas Group C differed statistically from both Groups A (P , 0.000001) and B (P ¼ 0.000003) to a significant extent. By the end of the 3-year follow-up period, 47% of the Group C patients had undergone permanent pacemaker implantation (DDDR)—Kaplan–Maier survival curves predict only 35% survival without pacing—whereas none did so in Groups A and B. Conclusions In patients with deficient chronotropic response to atropine administration, isoproterenol tests could differentiate those with inadequate chronotropic reserves, possibly requiring preventive pacemaker implantations.

Effects of atropine sulfate and neostigmine on gastric electrical activity in human subjects--electrogastrographic study.

Abstract: Background/Aims: There are few reports about the cholinergic regulation of gastric electrical activities using percutaneous electrogastrograms (EGG). To determine the effect of intravenous administration of a vagal blocker (atropine sulfate) or a vagal stimulator (neostigmine) on gastric electrical activities EGG was utilized in this study. Methodology: EGG was recorded before and after administration of a vagal blocker (atropine sulfate, 0.02mg/kg) and/or vagal stimulator (neostigmine, 0.008mg/kg) in six normal volunteers. Results: After administration of atropine sulfate, the original waves on EGG almost disappeared and decreased amplitudes were detected by visual inspection in all subjects. Moreover, increase amplitude on EGG was clearly demonstrated after administration of neostigmine in all subjects. It was also shown that the effects of these medicines persisted more than 60 minutes after injection. Conclusions: These findings suggest that the EGG reflected gastric motility, and that neurological regulation of EGG was mediated through the vagal and/or cholinergic efferent pathway.

Antifibrillatory actions of cisatracurium: an atrial specific M2 receptor antagonist.

Abstract: Introduction: Muscarinic receptor antagonists are proposed to prevent atrial fibrillation (AF), but also facilitate AV conduction, limiting clinical usefulness. Methods: Cisatracurium, a neuromuscular blocker, was administered to anesthetized dogs (0.05–0.8 mg/kg IV) and was administered to superfused pulmonary vein (PV) tissues in vitro. Results: Dose-dependent suppression of AF induced by premature atrial stimuli was observed under control conditions (n = 3), right vagus nerve stimulation (n = 7), and anterior right ganglionated plexus stimulation (n = 3). AF was prevented (P < 0.0001) concurrent with suppression of the decreased atrial MAP duration/ERP accompanying vagus nerve stimulation without altering AH intervals or sinus cycle length. Although atropine (0.001–0.016 mg/kg, n = 4) suppressed AF (P < 0.04) in association with suppression of atrial MAP shortening induced by vagus nerve stimulation, atropine also prevented sinus cycle length and AH interval prolongation with vagus nerve stimulation, and decreased AV effective and functional refractory periods. In vitro, both cisatracurium and atropine prevented (1) action potential shortening produced by acetylcholine administration and (2) action potential shortening and arrhythmia triggering within PV sleeves produced by local autonomic nerve stimulation, atropine producing competitive inhibition, and cisatracurium producing noncompetitive M2 muscarinic receptor blockade. Conclusions: Cisatracurium demonstrates a dose-dependent (1) suppression of AF and atrial action potential shortening accompanying vagus nerve stimulation without facilitating sinus or atrioventricular nodal function and (2) noncompetitive blockade of action potential shortening and triggered firing induced in isolated PVs by local autonomic nerve stimulation. The data are consistent with allosteric binding of cisatracurium to the M2 muscarinic receptor in canine atrium.

Antifibrillatory properties of mivacurium in a canine model of atrial fibrillation.

Abstract: The electrophysiologic actions of the competitive neuromuscular blocker mivacurium (0.05-0.8 mg/kg IV; N = 10) and atropine sulfate [0.01-0.16 mg/Kg intravenously (IV), N = 6] were determined under control conditions, during right vagus nerve stimulation, and during anterior right ganglionated plexus stimulation. Both drugs suppressed shortening of right atrial monophasic action potential (MAP) duration, right atrial refractoriness, and right superior pulmonary vein sleeve refractoriness produced by vagus nerve or ganglionated plexus stimulation and suppressed the induction of atrial fibrillation. Suppression of atrial fibrillation by atropine was accompanied by improved sinus and atrioventricular (AV) nodal function, increasing the ventricular heart rate observed during sinus rhythm and atrial fibrillation and eliminating the depressant actions of vagus nerve stimulation on sinoatrial (SA) and AV nodal function. Unlike atropine, mivacurium selectively antagonized the effects of vagus nerve and ganglionated plexus stimulation on atrial and pulmonary vein sleeve myocardium (shortening of action potential duration/refractoriness and increased atrial vulnerability) without altering sinus or AV nodal function under control conditions or during vagus nerve stimulation. The selective inhibition of parasympathetic nervous system effects in atrium versus sinus and AV nodes by mivacurium may represent a selective mechanism for the suppression of atrial fibrillation without altering SA and AV nodal function.

Effects of mepyramine and famotidine on the physostigmine-induced antinociception in the formalin test in rats.

Abstract: In this study, the effects of mepyramine (H1-receptor antagonist), famotidine (H2-receptor antagonist), physostigmine (a cholinesterase inhibitor) and atropine (muscarinic-receptor antagonist) have investigated on the formalin-induced nociception in rats. The effects of mepyramine and famotidine have also examined on nociceptive changes induced by physostigmine and atropine. Nociception was induced by intraplantar injection of formalin (50 microL, 1%) into the right hind paw and the time spent licking and biting of the injected paw, was taken as a measure of pain. Formalin induced a marked biphasic (first phase: 0-5 min and second phase: 15-45 min) pain response. The used drugs did not change the first phase of formalin-induced pain. Subcutaneous injection of physostigmine significantly (p<0.05) suppressed pain. Subcutaneous injection of atropine alone did not change the intensity of pain, but pretreatment with atropine significantly (p<0.05) prevented physostigmine-induced antinociception. Intraperitoneal injections of mepyramine and famotidine significantly (p<0.05) decreased pain response. Mepyramine did not significantly change, but famotidine significantly (p<0.05) prevented analgesic effect of physostigmine on pain. Atropine did not inhibit the antinociceptive effects of both mepyramine and famotidine on formalin-induced nociception. These results indicate that physostigmine through muscarinic cholinergic receptors suppresses the pain induced by formalin. Both H1 and H2 receptor antagonists produce antinociception. Histamine H2, but no H1 antagonists may be involved in physostigmine-induced antinociception.

[Clinical observation of penehyclidine hydrochloride as the preanesthetic medication before operation for patients with cleft lip/palate].

Abstract: Objective To compare the effects of penehyclidine hydrochloride, atropine and scopolamine as the preanesthetic medication before operation for patient with cleft lip/palate(CL/P) who would undergo general anesthesia Methods 120 CL/P patients who would undergo general anesthesia with tracheal intubation as research objects were chosen The patients were divided into three groups randomly, group of penehyclidine hydrochloride (group PH), group of atropine(group ATR) and group of scopolamine(group SCO), 40 patients in each group Penehyclidine hydrochloride(001 mg/kg), atropine(001 mg/kg) or scopolamine(0006 mg/kg) was given respectively to the patients The changes of heart rate, temperature, blood pressure and the secretion of respiratory tract were observed before medication, 15 minutes and 30 minutes after medication, after trachea cannula and after operation Results There were no significant changes in heart rate, temperature and blood pressure in group PH after medication(P005) The heart rate and temperature in group ATR and group SCO increased significantly after medication(P005), however, the blood pressure had no obvious change(P005) The secretion of respiratory tract was decreased significantly in group PH comparing to group ATR and group SCO when the operation was over(P 005) Conclusion Penehyclidine hydrochloride has no significant effect on heart rate, temperature and blood pres-sure to the patients, and it′s effect of secretion inhibition is longer and it is better than atropine and scopolamine

Chronic atropine administration diminishes the contribution of vasoactive intestinal polypeptide to heart rate regulation.

Abstract: Vasoactive intestinal polypeptide (VIP) is implicated in the modulation of vagal effects on the heart rate. In this study, the impact of acute and chronic atropine administration on VIP levels in rat heart atria was investigated in relation to heart rate in the course of vagus nerves stimulation. Anaesthetised control and atropinised (10 mg/kg/day for 10 days) rats pretreated with metipranolol and phentolamine that were either given or not a single dose of atropine were subjected to bilateral vagus nerve stimulation (30 min: 0.7 mA, 20 Hz, 0.2 ms). VIP concentrations in the atria were determined after each stimulation protocol. In control rats with or without single atropine administration, the heart rate upon vagal stimulation was higher than in atropinised animals with or without single atropine dose, respectively. VIP concentrations in the control atria were significantly decreased after the stimulation; the decrease was comparable both in the absence and presence of a single dose of atropine. Compared to controls, VIP levels were significantly decreased after chronic atropine treatment and they were not further reduced by vagal stimulation and single atropine administration. Administration of VIP antagonist completely abolished the differences in the heart rate upon vagal stimulation between control and atropinised groups. In conclusion, the data indicate that chronic atropine administration affects VIP synthesis in rat heart atria and consequently it modifies the heart rate regulation.

Regulation of Gastric Corpus Tone by the Vagus Nerve in the Ferret

Abstract: The pressure-volume relationship of the ferret gastric corpus was investigated to quantify the relative contributed of cholinergic and nonadrenergic, noncholinergic (NANC) mechanisms to the volume-accommodating property of this region. In splanchnectomized animals under control conditions the pressure-volume relationship of the corpus fitted a linear regression (Y = 0.30X + 0.57). Atropine decreased the magnitude of the pressure rise per unit volume, while after vagotomy this effect was reversed. The magnitude of these pressure changes in individual animals was consistent with reciprocal regulation of cholinergic and NANC pathways. Moreover, after vagotomy the shape of the pressure-volume curve was altered such that the pressure rise per unit volume was greater at the lower distending volumes. Continuous, low-frequency electrical vagal stimulation restored the pressure-volume relationship to that seen prior to vagotomy, an effect abolished by hexamethonium (25 mg/kg). Vasoactive intestinal polypeptide, on the other hand, caused a dose-related reduction in corpus pressure during the ramp increases in volume comparable to that seen during electrical stimulation but did not restore the shape of the pressure-volume curve. These data indicate that the action of the vagus may in part be permissive, with the sensitivity of local NANC pathways being modulated by a vagal cholinergic input.

Less tachycardia in adults when using atropine 0.9 mg compared with 1.2 mg plus neostigmine 2.5 mg.

Abstract: Objective: Compare the increase in heart rate in adults after 0.9 vs. 1.2 mg of atropine plus neostigmine 2.5 mg as the non-depolarizing muscle relaxant reversal agent. Material and Method: A randomized, double blind, controlled trial on 46 adults ASA I-II, undergoing elective gynecological or general surgery with balanced general anesthesia was performed. The subjects were randomized into two groups, After surgery, the study group received 0.9 mg of atropine, while the control group received 1.2 mg of atropine. Both groups received 2.5 mg of neostigmine simultaneously. Results: The heart rate and blood pressure were taken at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, and 30 min after the injection. The increase in heart rate and blood pressure between the two groups were compared. The heart rate (at 3, 4, 5, and 6 min) of patients in the study group increased significantly less than that of patients in the control group. There was no significant difference in blood pressure between groups and no side effects occurred. Conclusion: The authors conclude that 0.9 mg of atropine with 2.5 mg neostigmine can be safely used as the reversal agent for a non-depolarizing muscle relaxant, particularly in patients for whom any increase in heart rate would be harmful. Keywords: Agent, Atropine, Increase in Heart Rate, Reversal

Central Anticholinergic Syndrome Associated With Atropine: Case Report

Abstract: We report a case of anticholinergic syndrome after Atropine treatment for organophosphate poisoning in a young patient. Manifestations of anticholinergic syndrome may range from excitatory symptoms, including delirium and agitation, to central nervous system depression, stupor and coma. These reactions are related to the considerable interpersonal variation in susceptibility to Atropine, to the extent that toxic effects may occur at the usual therapeutic doses. Clinicians should watch for symtoms in patients with altered mental status following therapy with Atropine.

Involvement of cholinergic system in state-dependent learning induced by lithium in mice

Abstract: Objective: The influence of cholinergic drugs on lithium-induced statedependent learning has been investigated in adult male mice. Method: A single-trial step-down inhibitory avoidance task was selected. The drugs used in the study were lithium chloride physostigmine , nicotine hydrogen tartrate and scopolamine hydrobromide, atropine sulphate. The drugs were administrated through the peritoneal route. Control animals received saline or respective vehicle for nicotine. Ten animals were used in each experimental group. on day 1 or training session, the animals being trained in the step-down inhibitory avoidance task, and then immediately received post-training treatment of lithium or atropine or scopolamine. On day 2 or testing session, the animals firstly received pre-test administration of drugs (for nicotine 30 min, for lithium 45 min and for cholinergic antagonists 60 min before the test), and then were tested for step-down latency. Results: The results showed that post-training and pre-test intraperitoneal (i.p.) administration of lithium (10 mg/kg) induced state-dependent learning. In addition, pre-test administration of an anticholinesterase, physostigmine (0.3 and 0.6 mg/kg, i.p.) and nicotinic acetylcholine receptor agonist, nicotine (0.1 and 0.5 mg/kg) could substitute for pre-test lithium. Pre-test coadministration of an ineffective dose of physostigmine (0.1 mg/kg) but not nicotine (0.01 mg/kg), with lower doses of lithium (2.5 and 5 mg/kg) potentiated the effect of the latter drug on step-down latency. Post-training administration of a nonselective antagonist of muscarinic acetylcholine receptors, atropine, decreased the step-down latency, but pre-test administration of the same dose of the drug and also lithium, could not reverse the decrease of step-down latency. On the other hand, pre-test atropine at higher doses (0.3 and 0.6 mg/kg) disrupted lithium-induced statedependent learning. On the contrary, the decrease of step-down latency due to post-training administration of another nonselective muscarinic antagonist, scopolamine (1 mg/kg, i.p.) reversed by pre-test administration of not only the same dose of the drug, but also lithium (10 mg/kg). Interestingly, pre-test administration of scopolamine (1 mg/kg) also reversed the decrease of stepdown latency induced by post-training lithium (10 mg/kg). Conclusion: cholinergic system(s) may be involved in the lithium-induced state- dependent learning and the involvement of muscarinic receptors is more possible than nicotinic ones.