Search

Introduction: Postoperative myocardial revascularization atrial fibrillation (POAF) is a clinical complication that affects about 30% of patients and its mechanisms of origin are still poorly understood. This fact makes it difficult to identify the patient at greatest risk for this arrhythmia. This mission seems evident due to the complications it entails, including longer hospital stays, risk of stroke, heart failure, and death. There are reports of preoperative clinical aspects inherent to the patient's condition, such as gender and age, and discontinuation of beta-blockers as risk factors. In addition, additional information obtained by electrocardiogram, echocardiogram, and blood count data, for example, present only modest predictive results. The analysis of heart rate and heart rate variability obtained by the Stroke Risk Analysis System (SRA) is a technique used to predict ambulatory atrial fibrillation (AF), using recordings of only one hour showing good accuracy. This system, however, has not yet been used to predict the emergence of POAF. The rationale for its use is based on the suspicion that the emergence of POAF is strongly related to sympatho-vagal imbalance and the increase in atrial ectopia, that is, changes in heart rhythm, the main variables analyzed by the SRA algorithm., Objective: To assess the accuracy of the SRA to identify patients at risk of having POAF after coronary artery bypass graft surgery (CABG)., Method: 114 consecutive patients with coronary artery disease underwent coronary artery bypass grafting between the years 2015 and 2018. Between the first and fifth postoperative days, they underwent continuous electrocardiographic monitoring using the Holter system for cardiac rhythm analysis. Patients were divided into two groups: Group I was formed of those with POAF and Group II included patients without POAF. The tracings obtained by Holter were reanalyzed using the CardioManager®/Cardios program, converted and divided into one-hour sections using the SRA®/Cardios and Geratherm Converter program and submitted to the SRA-Apoplex medical/Geratherm® analysis algorithm. The SRA identifies three possibilities for classifying patient risk: a) Risk 0: patient in sinus rhythm; b) Risk 1: patient at increased risk for paroxysmal AF; c) Risk 2: patient with AF already present. For Group I, SRA were considered positive when Risks 1 and 2 were identified. For Group II, those identified as Risk 0 were considered negative SRA., Results: POAF occurred in 33/114 patients (28%). The sensitivity, specificity, positive predictive value, and negative predictive value of the SRA to identify patients with POAF were 69%, 84%, 69%, and 82%, respectively; the positive and negative likelihood ratios, in addition to the accuracy of the SRA were, respectively, 4.3%, 0.36%, and 79%. A subanalysis of the results of the day on which AF occurred was performed on the records obtained in the first three hours of recording and up to three hours before the appearance of POAF. In the first period, the SRA was able to predict POAF in 57% of cases, while in the second period, the system identified the arrhythmia in 83% of cases., Conclusions: a) The SRA presents good accuracy to predict POAF; b) its accuracy is moderate in the first three hours of recording; c) the accuracy increases significantly near the beginning of POAF; d) these findings indicate that electrophysiological changes that precede POAF are acute, occurring a few hours before the event and are identified by the SRA algorithm., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Serafim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

The neural histaminergic system modulates cognitive performance in various animal models. However, little is known about the effects of the H4 histaminergic receptor in the central nervous system. The purpose of this study was to investigate the effect of histaminergic H4 agonist VUF-8430 microinjection into the cerebellar vermis on the consolidation of emotional memory in mice subjected to the elevated plus maze (EPM) and inhibitory avoidance task (IAT). All experiments were performed on two consecutive days: exposure (T1 and D1) and 24h after, which we called re-exposure (T2 and D2). The animals received saline (SAL) or VUF (0.15 nmol; 0.49 nmol; 1.48 nmol/0.1μl) administered post-exposure. Experiment 1 was conducted in the EPM, and the animals were free to explore the maze for 5min. In T1, immediately after exposure, the pharmacological treatment was given; in T2, there was only re-exposure to the EPM. Experiment 2 involved the IAT, and the pharmacological treatment was provided post-D1; in D2, the animals were only re-exposed to the IAT. In Experiment 1, increased open arm exploration (% open arm entries and% open arms time) for 0.49 and 1.48nmol of VUF were recorded in T2 compared to T1. In Experiment 2, a significant decrease in consolidation latency was recorded for the group that received 1.48nmol of VUF compared to the SAL group in D2. These results indicate that a 1.48nmol VUF microinjection into the cerebellar vermis impaired performance in both models, even though one model was anxiety-mediated (EPM) and the other was fear-mediated (IAT)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study investigated the effects of bilateral intraamygdalar microinjections of PNU-282987, a nicotinic cholinergic agonist, on anxiety and the reversal of amnesia induced by chlorpheniramine (CPA), an H1 histaminergic antagonist, in mice subjected to the elevated plusmaze (EPM). Two experiments were performed with seventy-nine adult male Swiss mice. The isolated microinjections of PNU-282987 did not produce effects on emotional memory; however, the combined microinjections of PNU-282987 and CPA were able to reverse the deficit in memory induced by CPA (ANOVA, p<0.05). Taken together, these results suggest that intraamygdalar injections of PNU-282987 did not induce effects on anxiety and emotional memory per se; however, concurrent microinjections of PNU-282987 and CPA-reverse amnesia induced-CPA which is suggestive of an interaction between the histaminergic and cholinergic systems in the modulation of emotion memory acquisition in mice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

H1 receptor histaminergic antagonist, chlorpheniramine (CPA) participates in cognitive performance in various animal models. However, little is known regarding the effects of CPA microinjection into the amygdala on emotional behavior. The purpose of this study was to investigate whether CPA microinjection into the amygdala has the same effect on two models, one anxiety- and the other fear-mediated, in various memory stages using the elevated plus maze (EPM) and the inhibitory avoidance task (IAT) tests. Two experiments were performed with seventy-two adult male Swiss mice. Behavioral testing was performed on two consecutive days, and in both experiments, before each trial, the animals received bilateral microinjections of saline (SAL) or CPA (0.16 nmol). The animals were re-exposed to the EPM or IAT 24h after the first trial. Four experimental groups were tested: SAL-SAL, SAL-CPA, CPA-SAL and CPA-CPA. In experiment 1, a decreased open arm exploration (% open arm entries, %OAE and% open arms time, %OAT) for SAL-SAL and SAL-CPA was showed, while these measures did not decrease for the CPA-SAL and CPA-CPA groups in Trial 2. In experiment 2, an increase of retention latency in relation to training 2 for the groups SAL-SAL and CPA-SAL and a significant decrease in latency for the group SAL-CPA was revealed. These results indicate that chlorpheniramine microinjection into the amygdala impairs emotional memory acquisition and/or consolidation in the EPM and retrieval of IAT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

The present study investigated the effect of thioperamide (THIO), an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM). We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure), the mice (n=10/group) were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL) immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms) compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA) followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL), indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL) microinjected into the cerebellum impaired emotional memory consolidation in mice.

This study investigated the role of H₁ and H₂ receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H₁ receptor, but not H₂, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have high density in the vermis and flocculus. Evidence indicates that the cerebellar vermis is involved in memory consolidation. Recently, we demonstrated that when histamine is microinjected into the cerebellar vermis it results in impaired emotional memory consolidation in mice that are submitted to the elevated plus maze (EPM). This study investigated whether histamine impairment was mediated by the H(1) or H(2) receptors. The cerebellar vermis of male mice (Swiss Albino) were implanted using a guide cannula. Three days after recovery, behavioral tests were performed in the EPM on two consecutive days (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL) or histamine (HA, 4.07 nmol/0.1 μl) was microinjected 5 min after pretreatment with the H(1) antagonist chlorpheniramine (CPA, 0.16 nmol/0.1μl) or SAL. In Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment with the H(2) antagonist ranitidine (RA, 2.85 nmol/0.1 μl) or SAL. Twenty-four hours later, the mice were re-exposed to the EPM (Trial 2) under the same experimental conditions but did not receive an injection. On both days, the test sessions were recorded to enable analysis of the behavioral measures. The decrease in open arm exploration (% entries and % time spent in the open arms) in Trial 2 relative to Trial 1 was used as a measure of learning and memory. The data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's tests. In Experiment 1, the Duncan's test indicated that the mice entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in Trial 2 after being microinjected with SAL+SAL, SAL+CPA and CPA+HA. However, the animals that received SAL+HA did not enter the open arms less frequently or spend less time in them, which was significantly different from the CPA+HA group. The results of Experiment 2 demonstrated that the %OAE and %OAT in Trial 2 were different from Trial 1 for the groups that were microinjected with SAL+SAL and SAL+RA. The animals that were microinjected with RA+HA or with SAL+HA did not show a reduction in %OAE. These results demonstrate that the animals treated with HA did not avoid the open arms less on retesting and indicated that CPA did not alter the behavior parameters but did revert the histamine-induced impairment of memory consolidation. Furthermore, the H(2) antagonist RA, at the dose used in this study, did not affect memory consolidation and failed to revert histamine-induced impairment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study investigated the role of amygdala H(1) receptors in state-dependent memory deficits induced by l-histidine (LH). Tests using an elevated plus-maze (EPM) were performed on two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before each trial, mice were intraperitoneally (IP) injected with LH (500mg/kg). Two hours later, they were microinjected with the H(1) receptor antagonist, chlorpheniramine (CPA 0.016, 0.052, or 0.16 nmol/0.1μl), or saline (SAL) into the amygdala and submitted to the EPM. LH-CPA did not affect trial 1 performances in the EPM, which indicated that these drugs did not affect anxiety. Emotional memory, as revealed by a reduction in open arm exploration between both trials, was present in the SAL-SAL groups as well as in the SAL-CPA groups for the lower doses of CPA (0.016 and 0.052nmol). On the contrary, neither the LH-SAL group nor the LH-CPA groups exhibited this decrease in open arm activity between both trials, which reveals that LH impaired emotional memory. While intra-amygdalar CPA did not interact with LH effect, it impaired per se the emotional memory performances at the highest dose (0.16nmol). No significant changes were observed in the number of enclosed arm entries (EAE), an EPM index of general exploratory activity. These results may be attributed to a combined effect in the different nucleus of the amygdala. Taken together, these results suggest that the H(1) receptors in the amygdala are not implicated in anxiety-like behaviors but are involved in emotional states induced by the T1/T2 EPM protocol in mice., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean +/- SEM; OAE: 4.0 +/- 0.71, 4.80 +/- 1.05; OAT: 40.55 +/- 9.90, 51.55 +/- 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 +/- 0.73, 4.87 +/- 0.66; OAT: 63.93 +/- 11.72, 63.58 +/- 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 +/- 0.66, T2: 5.47 +/- 1.05; T1: 63.58 +/- 10.22; T2: 49.01 +/- 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 +/- 1.60, T2: 4.70 +/- 1.04; T1: 51.55 +/- 12.10, T2: 43.88 +/- 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.