Efficacy of Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Supplementation on Psychological Stress and Selective Fitness Profile Parameters in Female College Students in West Bengal, India.

Psychological disparities impact physical activity and fitness in sedentary female college students by affecting cardiovascular efficiency. Ganoderma lucidum, vitality-enhancing herb alleviates health and rejuvenates the mind-body to improve endurance fitness. A double-blinded, randomized, placebo-controlled parallel design study was conducted to determine whether supplementation of G. lucidum in daily dosages of 500 mg (GL500mg group) and 1000 mg (GL1000mg group) improves psychophysiological health capabilities during the different phases of the experimental trial. Analysis for pre-experimental trial (day 0), experimental trial (day 15), and post-experimental trial (after day 30) on anthropometric, psychological, physiological, and physical fitness parameters were executed. Seventy-eight participants (n = 78, age 20.64 ± 3.21 years) were assigned randomly and equally divided (n = 26) to one of the three treatment groups for intragroup and intergroup comparisons. Significant differences in the post-experimental GL1000mg group for heart rate (HR), maximal oxygen consumption (VO2max), physical work capacity (PWC170), and right-hand grip strength (P < 0.05) compared with the placebo group were observed. GL1000mg-supplemented group also significantly improved (P < 0.05) HR, VO2max and PWC170 (P < 0.001) after pre- to post-trials. Experimental trial between placebo and GL1000mg group and post-experimental trial between the GL500mg and GL1000mg group showed significant changes in VO2max(P < 0.001) and PWC170 (P < 0.05). Anxiety, depression, vitality and positive well-being scores significantly improved, leading to improved psychological well-being after GL1000mg supplementation. GL1000mg supplementation for 30 days might act as a longevity-promoting tonic for endurance and strength performance by ameliorating stress to improve the overall psychophysiological health, vitality and quality of life for better cardiovascular efficacy.

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants.

The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human subjects. This analysis is based on nine double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25-200 µg LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models and Least Absolute Shrinkage and Selection Operator regression. Results were adjusted for LSD dose and corrected for multiple testing. LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as "Well-Being", "Emotional Excitability", and "Anxiety" were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait "Openness to Experiences" was positively correlated with elevated ratings in "Oceanic Boundlessness" and mystical-type effects. Previous experiences with hallucinogens have been negatively associated with the overall altered state of consciousness and particularly with "Anxious Ego Dissolution". Acute anxiety negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme. In summary, besides the amount of drug consumed, non-pharmacological factors such as personal traits and current mood also significantly predicted the subjective drug experience. Sex and body weight were not significant factors in influencing the drug experience.

Chronic acetylcholinesterase inhibition reduces the effects of physical training on ventricular contractility and coronary bed reactivity in hypertensive rats.

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and ß-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains.

The interplay of brain neurotransmission and mental fatigue: A research protocol.

INTRODUCTION: Mental fatigue (MF) significantly affects both cognitive and physical performance. However, the precise mechanisms, particularly concerning neurotransmission, require further investigation. An implication of the role of dopamine (DA) and noradrenaline (NA) is stated, but empirical evidence for this theory still needs to be provided. To address this gap, we aim to investigate the role of brain neurotransmission in elucidating if, and how prolonged cognitive activity induces MF and its subsequent impact on cognitive performance. METHODS: This study (registration number: G095422N) will adopt a randomized cross-over design with sixteen healthy participants aged 18-35 years. The sessions include a familiarization, two experimental (DA: 20mg Methylphenidate; NA: 8mg Reboxetine) conditions, and one placebo (lactose tablet: 10mg) condition. A 60-minute individualized Stroop task will be used to investigate whether, and how the onset of MF changes under the influence of reuptake inhibitors. Attention and response inhibition will be assessed before and after the MF-inducing task using a Go/NoGo task. The integration of physiological (electroencephalography, heart rate), behavioral (attention, response inhibition), and subjective indicators (scales and questionnaires) will be used to detect the underlying mechanisms holistically. Data analysis will involve linear mixed models with significance at p<0.05. DISCUSSION: The integration of diverse techniques and analyses offers a comprehensive perspective on the onset and impact of MF, introducing a novel approach. Future research plans involve extending this protocol to explore the connection between brain neurotransmission and physical fatigue. This protocol will further advance our understanding of the complex interplay between the brain and fatigue.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

Epigallocatechin gallate enhances sympathetic heart rate variability and decreases blood pressure in obese subjects: a randomized control trial.

This study aimed to investigate effects of epigallocatechin gallate (EGCG) on blood pressure (BP) and autonomic nervous system, indicated by 5-min heart rate variability (HRV) measurement in obese subjects, and determine correlations of BP with metabolic factors. In a double-blind, randomized controlled trial, obese subjects (n = 30) were randomly allocated to receive 150 mg EGCG (n = 15) or placebo (n = 15) twice a day without dietary restrictions. After 8-week EGCG treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) significantly decreased, while the low-frequency (LF) to high-frequency power (HF) ratio (LF/HF ratio) significantly increased (P < 0.05 all), indicating a shift toward sympathetic dominance, either directly or indirectly after BP lowering. SBP had positive correlations with obesity parameters, leptin, insulin, and insulin resistance but had a negative correlation with insulin sensitivity. DBP was positively correlated with age and HF in normalized unit, but negatively correlated with height and LF in ms2. High-density lipoprotein cholesterol (HDL-C) was negatively correlated with SBP, DBP, and MAP reflecting its protective effect against elevated BP. In conclusion, the 8-week EGCG treatment decreased BP and increased the LF/HF ratio, reflecting increased sympathetic activity, either a direct EGCG effect or an indirect compensatory response following BP reduction.

Effect of high-dose ß-Alanine supplementation on uphill cycling performance in World Tour cyclists: A randomised controlled trial.

Scientists and coaches seek effective ergogenic aids for performance improvement. Cyclists commonly use ß-Alanine, which may enhance post-exercise recovery and physical performance. High-dose ß-Alanine supplementation's impact on World Tour cyclists during a 7-day camp remains unstudied. This study aimed to analyse the effect of a high dose of ß-alanine in World Tour cyclist during a 7-day camp. A double-blinded, randomised controlled trial was conducted. 11 cyclists were included in the final analysis: ß-alanine supplementation (n = 5; VO2max: 67.6±1.6 ml/kg/min) and a placebo group (n = 6; VO2max: 68.0±2.4 ml/kg/min). The duration of the supplementation protocol was seven days with four daily intakes. The subjects commenced supplementation after the physical tests (immediately following the snack) and consumed the final intake after breakfast on the day of the final test (a total of 7 days and 3 additional doses, 31 servings in total; 5g per dosage; 155g the total cumulative amount). Before and after seven days of supplementation, the cyclists performed an uphill time trial. Blood lactate, heart rate and rating of perceived exertion were measured during test. ß-alanine supplementation improved the relative mean power attained during the time-trial compared with the control group (Z = -2.008; p = 0.045; Δ = 0.060), as well as the time needed to complete this trial (Z = -2.373; p = 0.018). As for physiological and metabolic variables, no significant change was found. In conclusion, the present study supports the effectiveness of one-week high dose of ß-alanine during a cycling training in World Tour cyclists to improve their uphill time-trial performance. In addition, it is important to highlight the potential role of ß-alanine in improving recovery power. This aspect is particularly relevant in the context of a training camp, where fatigue levels can increase alongside training intensity. Trial registration: This study was registered in ClinicalTrials.gov: (identifier: NCT04427319).

A Photoactivatable Version of Ivabradine Enables Light-Induced Block of HCN Current In Vivo.

Therapeutic drugs, whose bioactivity is hindered by a photoremovable cage, offer the advantage of spatiotemporal confinement of their action to the target diseased tissue with improved bioavailability and efficacy. Here, we have applied such an approach to ivabradine (IVA), a bradycardic agent indicated for angina pectoris and heart failure, acting as a specific HCN channel blocker. To overcome the side effects due to its poor discrimination among HCN channel subtypes (HCN1-4), we prepared a caged version of IVA linked to a photocleavable bromoquinolinylmethyl group (BHQ-IVA). We show that upon illumination with blue light (440 nm), BHQ-IVA releases active IVA that blocks HCN channel currents in vitro and exerts a bradycardic effect in vivo. Both BHQ-IVA and the cage are inactive. Caging is stable in aqueous medium and in the dark, and it does not impair aqueous solubility and cell permeation, indispensable for IVA activity. This approach allows for bypassing the poor subtype-specificity of IVA, expanding its prescription to HCN-related diseases besides cardiac.

ß-ionone inhibits the grazing of Daphnia sinensis by reducing the activity of acetylcholinesterase.

ß-ionone is a volatile metabolite of Microcystis aeruginosa that is toxic to aquatic organisms. Using Daphnia sinensis as model, our present study found that ß-ionone could significantly reduce heart rate and feeding rate, and induce intestinal emptying. Transcriptomic analysis showed that ß-ionone could significantly inhibit the expression of acetylcholinesterase (AchE) mRNA, while metabolomics further revealed that ß-ionone could significantly increase the level of acetylcholine (Ach) in D. sinensis. These results indicated that ß-ionone might act as an AchE inhibitor, resulting in an increase in Ach levels. To test this hypothesis, both in vivo and in vitro experiments demonstrated that ß-ionone could significantly reduce AchE activity. Furthermore, the inhibitory effects of ß-ionone on heart rate and feeding rate could be blocked by the M-type Ach receptor (mAchR) blocker. These findings confirm that ß-ionone is a novel AchE inhibitor. ß-ionone could inhibit the activity of AchE, which in turn resulted in an increase of Ach in D. sinensis. Consequently, elevated levels of Ach could suppress the heart rate and feeding rate of D. sinensis by activating the mAchR, while concurrently accelerating the rate of intestinal emptying by stimulating intestinal peristalsis, thereby obstructing the digestion of algae within the intestinal tract.

Comparison of Remimazolam and Dexmedetomidine for Sedation in Awake Endotracheal Intubation in Scoliosis Surgery: A Retrospective Analysis.

BACKGROUND Awake endotracheal intubation (AEI) involves the placement of an endotracheal tube in patients who can maintain spontaneous respirations. This retrospective study aimed to compare sedation with remimazolam during AEI with that of dexmedetomidine in patients who underwent scoliosis correction surgery. MATERIAL AND METHODS This is a retrospective study based on data from 98 patients who had AEI procedures between January and December 2023. The remimazolam group included 55 patients, and the dexmedetomidine group included 43 patients. Remimazolam 0.05 mg/kg was injected 1 min before intubation, while dexmedetomidine 1 ug/kg was pumped 10 min before intubation. Evaluations of AEI, hemodynamics, and respiratory adverse events were then compared between the 2 groups. RESULTS There was no significant difference in demographic data between the groups. After administrating sedation, dexmedetomidine led to a larger reduction of mean arterial pressure (MAP) and heart rate (HR) than did remimazolam (11.30±1.86 vs 8.33±2.28 mmHg, P<0.001; 12.28±2.50 vs 2.85±1.82 beats/min, P<0.001). When conducting intubation, the increase of MAP in the remimazolam group was lower than that in the dexmedetomidine group (7.40±2.81 vs 9.26±5.08 mmHg, P=0.024), while the difference in HR change was not significant (7.53±5.41 vs 8.37±5.31 beats/min, P=0.441). When combined with local anesthesia, the success rate of AEI, time of AEI procedure, attempt times, increase of MAP during intubation, depth of sedation, and respiratory adverse events were comparable between the groups (P>0.05). CONCLUSIONS With local anesthesia, remimazolam and dexmedetomidine sedation can facilitate AEI for patients with scoliosis. However, remimazolam is associated with more stable hemodynamics.

Crocus Sativus Linnaeus (Saffron) intake does not affect physiological and perceptual responses during a repeated sprint test in healthy active young males.

The study aimed to investigate the effects of acute ingestion of saffron (SAF) on physiological (i.e., heart rate and blood lactate) and perceptual (i.e., ratings of perceived exertion [RPE] and feeling scale) measures in response to a repeated-sprint ability test (RSS) in healthy young males (N = 22; mean ± SD: age, 21.7 ± 1.24 yrs.). All participants completed two experimental trials with a one-week washout period using a double-blind, placebo-controlled, crossover design. In each session, the participants were randomly chosen to receive either a capsule of saffron (300 mg) (SAF session) or a capsule of lactose (PLB session) two hours before performing the RSS.No significant differences (p > 0.05) were found for heart rate, RPE, and feeling scale between the SAF or PLB sessions at pre- and post-RSS. There were no significant changes (p > 0.05) in peak time, total time, fatigue index, and blood lactate in either the SAF or PLB sessions. Acute SAF ingestion did not significantly improve RSS performance nor physiological and perceptual measures in active young males. Future trials should address the topic by using shortened/prolonged higher doses of SAF on biological, physical, physiological, and perceptual responses to acute and chronic exercise.

The role of esmolol in sepsis: a meta-analysis based on randomized controlled trials.

BACKGROUND: Sepsis is associated with a high incidence and mortality and poses a significant challenge to the treatment. Although esmolol has shown promise in sepsis treatment, its efficacy and safety remain contentious. This meta-analysis aims to clarify the role of esmolol in sepsis management. METHODS: PubMed, Embase, Web of Science, Cochrane library, clinicaltrials.gov and the Chinese Clinical Trial Registry were searched and references of relevant reviews and meta-analysis were also screened for appropriate studies. Keywords and free words of 'sepsis', 'esmolol' and 'randomized controlled trials' were used for search. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Fifteen studies involving 1100 patients were included. Compared with the control group, patients receiving esmolol exhibited significantly decreased 28-day mortality (RR, 0.69; 95% CI, 0.60 to 0.81; P < 0.0001), heart rate (HR) (SMD, -1.15; 95% CI, -1.34 to -0.96; P < 0.0001), cardiac troponin I levels (cTnI) (SMD, -0.88; 95% CI, -1.13 to -0.64; P < 0.0001), length of intensive care unit (ICU) stay (SMD, -0.46; 95% CI, -0.62 to -0.3; P < 0.0001) and duration of mechanical ventilation (SMD, -0.28; 95% CI, -0.48 to -0.09; P = 0.004) and significantly increased central venous oxygen saturation (ScvO2) (SMD, 0.66; 95% CI, 0.44 to 0.88; P < 0.0001).While, esmolol had no significant influence on norepinephrine dosage (SMD, 0.08; 95% CI, -0.13 to 0.29; P = 0.46), mean arterial pressure (MAP) (SMD, 0.17; 95% CI, -0.07 to 0.4; P = 0.16), central venous pressure (CVP) (SMD, 0.16; 95% CI, -0.04 to 0.35; P = 0.11) and left ventricular ejection fraction (LVEF) (SMD, 0.21; 95% CI, -2.9 to 0.7; P = 0.41). CONCLUSION: Esmolol reduces 28-day mortality, length of ICU stay and duration of mechanical ventilation in sepsis patients. Furthermore, esmolol improves oxygen metabolism, mitigates myocardial injury and decreases heart rate without significantly affecting hemodynamic parameters. TRIAL REGISTRATION: This study was registered on the PROSPERO website (registration number: CRD42023484884).

Effect of different anesthesia depths on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia.

BACKGROUND: To analyze the effects of different anesthesia depths on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, and to provide a basis for clinical application. METHODS: A total of 111 patients with gastric cancer who were treated with epidural anesthesia combined with general anesthesia were selected as the study subjects, and the patients were randomly divided into group A, group B and group C. The bispectral index (BIS) was maintained by adjusting the infusion speed of anesthetics, the BIS of group A was maintained at 50 ~ 59, the BIS of group B was maintained at 40 ~ 49, and the BIS of group C was maintained at 30 ~ 39. The high-frequency power (HFP), low-frequency power (LFP), total power (TP), mean arterial pressure (MAP), heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured before anesthesia induction (T1), immediately after intubation (T2), 3 min after intubation (T3), and 6 min after extubation (T4). The cognitive function of the patients was evaluated before and 48 h after surgery. RESULTS: The HFP, LFP/HFP, TP, HR, DBP and SBP between the three groups at T1 ~ T3 are significantly difference from each other (P < 0.05). There were significant differences in spontaneous breathing recovery time, eye opening time and extubation time among group A, B and C groups, and group B had the lowest spontaneous breathing recovery time, eye opening time and extubation time (P < 0.05). There was no significant difference in the incidence of adverse reactions during anesthesia between the three groups. The cognitive function score of group B was significantly higher than that of group A and group C (P < 0.05). CONCLUSIONS: BIS maintenance of 40 ~ 49 has little effect on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, which is helpful for postoperative recovery.

[The role of magnesium sulfate in providing hemodynamic stability in patients undergoing laparoscopic surgery: a prospective randomized controlled study]. / Intérêt du sulfate de magnésium pour la stabilitée hémodynamique en cœliochirurgie: étude prospective contrôlée randomisée.

Introduction: during laparoscopic surgery, carbon dioxide (CO2) insufflation to create pneumoperitoneum increases blood pressure, heart rate and systemic vascular resistance. The purpose of our study was to investigate the efficacy of magnesium sulfate in preventing adverse hemodynamic reactions associated with pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. Methods: we conducted a prospective, randomized, double-blind, controlled clinical study of patients scheduled for laparoscopic cholecystectomy and divided into two equal groups: the Mg2+ group received slow intravenous magnesium sulfate 50 mg/kg injection prior to pneumoperitoneum insufflation while the S group received the same volume of 0.9 % saline. Our primary endpoint was intraoperative changes in systolic blood pressure (SBP) related to pneumoperitoneum, in particular at 1 minute after insufflation. The secondary endpoints were the haemodynamic effects of pneumoperitoneum in terms of systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP) and heart rate (HR) from 2 minutes after insufflation to extubation and postoperatively, and the presence of possible adverse reactions related to the administration of magnesium sulphate. Results: we included 70 patients divided into two groups of 35. SP was significantly higher in the S group at insufflation (T0), 3 min, 4 min and 5 min post-operative, and at 60 min after surgery. HR was significantly higher in patients in the S group compared to the Mg2+ group at 7 min and 8 min after insufflation. No significant differences in DP and MAP measurements were observed between the 2 groups. No adverse reactions related to magnesium administration were reported. Conclusion: magnesium sulfate administered prior to pneumoperitoneum insufflation provided improved intraoperative hemodynamic stability during laparoscopic surgery.

CARDIORESPIRATORY EFFECTS OF VATINOXAN IN BLESBOK (DAMALISCUS PYGARGUS PHILLIPSI) IMMOBILIZED WITH THIAFENTANIL-MEDETOMIDINE.

Combinations of a low dose of opioid, such as thiafentanil, and a high dose of medetomidine, are increasingly being used for immobilization of African ungulates. Both drugs can have undesirable cardiorespiratory effects. In this study we assessed whether vatinoxan, a peripherally acting alpha2-adrenergic receptor antagonist, can be used to alleviate some of these effects without affecting the immobilization quality. Eight healthy, female, boma-confined blesbok (Damaliscus pygargus phillipsi), weighing a mean (SDtion) of 56.8 (4.4) kg, were immobilized twice in a randomized cross-over study with a 2-wk washout period using (1) 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), (2) TM + vatinoxan: 0.5 mg thiafentanil + 1.5 mg medetomidine + 15 mg vatinoxan per milligram medetomidine (total of 22.5 mg, administered intramuscularly at 10 min post recumbency). Heart rate, respiratory rate, rectal temperature, oxygen saturation (SpO2), arterial blood pressure, and sedation scores from 1 to 5 (1 = limited effect; 5 = excessively deep) were measured every 5 min. Arterial blood gases (PaO2 and PaCO2) were measured at 10, 15, 25, and 35 min postrecumbency and the alveolar--arterial oxygen gradient (P[A-a]O2) was calculated. Induction times and immobilization quality did not differ between groups. The heart rate was significantly higher and the mean arterial pressure significantly lower in blesbok after receiving vatinoxan. All animals were hypoxemic and there were no significant differences in the respiratory rates, PaO2, PaCO2, SpO2, or P(A-a)O2 gradients at any time point. Although vatinoxan did not improve respiratory variables and blood oxygenation in these animals, the change in cardiovascular variables may suggest that it improves tissue perfusion, a positive outcome that requires further investigation.

ß-Adrenergic receptor signalling pathway mediated antiarrhythmic activity of s-limonene in the rat heart.

S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of ß-adrenoceptor (ß-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the ß-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 µM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 µM and reduced heart rate at the concentrations of 30 (12.4%) and 50 µM (16.6%). s-Lim (10 µM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 µM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker ß1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists ß1-AR), presenting a similar effect to propranolol (a non-selective blocker ß-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 µM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of ß-AR in the heart.

Does a single oral administration of amiloride affect spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults?

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults.NEW & NOTEWORTHY Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.

Limited evidence that alcohol affects emotional face processing via interoceptive pathways, a registered report.

BACKGROUND: Our brain uses interoceptive signals from the body to shape how we perceive emotions in others; however, whether interoceptive signals can be manipulated to alter emotional perceptions is unknown. This registered report examined whether alcohol administration triggers physiological changes that alter interoceptive signals and manipulate emotional face processing. METHODS: Participants (n=36) were administered an alcohol or placebo beverage. Cardiovascular physiology (Heartrate variability, HRD) was recorded before and after administration. Participants completed a behavioral task in which emotional faces were presented in synchrony with different phases of the cardiac cycle (i.e., systole/diastole) to index of how interoceptive signals amplify them. HYPOTHESES: We hypothesized that alcohol administration would disrupt the cardiac amplification of emotional face processing. We further explored whether this disruption depended on the nature and magnitude of changes in cardiovascular physiology after alcohol administration. RESULTS: We observed no main effects or interactions between alcohol administration and emotional face processing. We found that HRV at baseline negatively correlated with the cardiac amplification of emotional faces. The extent to which alcohol impacted HRV negatively correlated with the cardiac amplification of angry faces. CONCLUSIONS: This registered report failed to validate the primary hypotheses but offers some evidence that the effects of alcohol on emotional face processing, if any, could be mediated via changes in basic physiological signals that are integrated via interoceptive mechanisms. Results are interpreted within the context of interoceptive inference and could feed novel perspectives for the interplay between physiological sensitivity and interoception in the development of drug-related behaviors.

Complete autonomic blockade reveals nitric oxide contribution to blood pressure regulation in obese Black women.

PURPOSE: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion. METHODS: L-NMMA at doses of 250 µg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure. RESULTS: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m2), and nine White women (age range 30-50 years, body mass index 30-45 kg/m2) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively). CONCLUSION: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women. REGISTRATION: ClinicalTrials.gov: NCT01122407.

Sex-dependent effects of antimicrobials and lipopolysaccharide on blood-brain-barrier permeability in pubertal male and female CD1 mice.

Exposure to stressors during puberty can disrupt normal development and possibly increase susceptibility to neurodegenerative disorders later in life. However, the mechanisms underlying the relationship between pubertal stress exposure and neurodegeneration remain unclear. As such, the current study was designed to examine the effects of pubertal antimicrobial (AMNS) and lipopolysaccharide (LPS) treatments on intestinal and blood-brain-barrier (BBB) permeability in male and female mice. Moreover, we also examined the sex-specific effects of pubertal AMNS and LPS treatments on gross motor activity, heart rate, and core body temperature. At four weeks of age, male and female CD1 mice were implanted with the G2 HR E-Mitter telemetry system. At five weeks of age, mice received 200 µL of broad-spectrum antimicrobial or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal injection of either saline or LPS at six weeks of age. BBB and intestinal permeability were examined 24 h, 72 h, and one week post-LPS/saline treatment. Telemetric data was collected for 48 h post-LPS/saline treatment. The results showed that pubertal AMNS and LPS treatments increased sickness behaviours and decreased body temperature and heart rate, in a sex-dependent manner. Furthermore, pubertal AMNS and LPS treatments resulted in sex-dependent regional increases in BBB permeability 24 h and 72 h post-LPS/saline treatment, while global increases in BBB permeability were only observed one week post-LPS/saline treatment. These results further our understanding of the combined effects of AMNS and LPS treatments on physiology and on the enduring negative changes observed following pubertal exposure to stressors.