Plasma Catecholamine Concentrations Research Articles

Sublingual sufentanil does not decrease tolerance to progressive central hypovolemia

Hemorrhage is a leading cause of death in both civilian and battlefield settings. Since pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic responses beneficial to maintaining arterial blood pressure and thus organ perfusion. Sublingual sufentanil is currently available for administration on the battlefield, but its effect on hemorrhage tolerance is unknown. This study tested the hypothesis that sufentanil impairs tolerance to progressive central hypovolemia in awake humans. METHODS: 29 participants, 15 males and 14 females (aged: 29 ± 5, weight: 74 ± 8 kg, BMI: 25 ± 2 kg/m2) participated in this double-blinded, randomized, placebo-controlled trial. Following sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) protocol starting at 40 mmHg that was further reduced by 10 mmHg every three minutes until presyncope. Presyncope was defined as: continued reports of feeling faint and/or nauseous, a rapid decline in blood pressure resulting in systolic blood pressure <80 mmHg, and/or relative bradycardia accompanied by a narrowing of pulse pressure. Tolerance to LBNP, quantified as cumulative stress index (mmHg*min), was compared between sufentanil and placebo trials using a Wilcoxon Signed rank test. Arterial blood pressure, heart rate, and plasma catecholamine concentrations were compared using mixed effects models (LBNP stage x Drug). RESULTS: Tolerance to LBNP was not different between trials (sufentanil: 518 ± 203 vs. placebo: 594 ± 267, p = 0.495). Mean blood pressure decreased similarly between the two trials during LBNP (sufentanil: -23 ± 9 mmHg vs. placebo: -22 ± 10 mmHg, p< 0.001), with no main effect of drug (p = 0.498) or interaction (p = 0.935). Increases in heart rate with LBNP were similar between the two trials (sufentanil: 44 ± 25 bpm vs. placebo: 52 ± 23 bpm, time: p < 0.001) with no main effect of drug (p=0.626) or interaction (p = 0.424). Epinephrine (drug: p = 0.004, time: p < 0.001, interaction: p = 0.031) and norepinephrine (drug: p = 0.017, time: p < 0.001, interaction: p = 0.161), concentrations increased to LBNP, with post hoc analysis revealing that epinephrine concentrations were higher at LBNP 50 and presyncope (p ≤ 0.05) with sufentanil. CONCLUSION: These data demonstrate that sublingual sufentanil does not impair tolerance to simulated hemorrhage or alter the assessed mechanisms responsible for maintaining arterial blood pressure. W81XWH-22-C-0004. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients. We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies. The CAN structures mainly include insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal gray. Autonomic dysfunction after ICH is closely associated with neurological functional outcomes, cardiac complications, blood pressure fluctuation, immunosuppression and infection, thermoregulatory dysfunction, hyperglycemia, digestive dysfunction, and urogenital disturbances. Heart rate variability, baroreflex sensitivity, skin sympathetic nerve activity, sympathetic skin response, and plasma catecholamine concentration can be used to assess the autonomic functional activities after ICH. Risk stratification of patients according to autonomic functional activities, and development of intervention approaches based on the restoration of sympathetic-parasympathetic balance, would potentially improve clinical outcomes in ICH patients. The review systematically summarizes the evidence of autonomic dysfunction and its association with clinical outcomes in ICH patients, proposing that targeting autonomic dysfunction could be potentially investigated to improve the clinical outcomes.

Cardiogenic pulmonary edema - is it lone cardiogenic? "Missing link" between hemodynamic and other existing mechanisms.

The current traditional pathophysiologic concept of pulmonary edema of cardiogenic origin explains its development by a hydrostatic effect due to increased pulmonary capillary pressure resulting in fluid flux to alveolar and interstitial areas from capillaries. However, several experimental studies and clinical data of poor response to hemodynamic and diuretic treatment in many scenarios provide further evidence of the involvement of several other contributing factors to the development of cardiogenic pulmonary edema. Several experimental and clinical studies have found that sympathetic overactivity with elevated plasma catecholamine concentrations may play an important role in the development of cardiovascular-associated pulmonary edema. Catecholamine-induced pulmonary injury may be one of the key mechanisms in acute cardiogenic pulmonary edema triggering proinflammatory cytokine overactivation, oxidative stress and myocardial injury. In the everyday treatment of acute heart failure, physicians should consider the possibility of other noncardiogenic mechanisms involved in the progression of acute pulmonary edema, particularly catecholamine overactivity, lymphatic drainage, inflammatory and oxidative stress, high surfactant protein. The classic, hemodynamic treatment approach in pulmonary edema with the coexistence of other contributing factors may not provide adequate clinical benefit during treatment.

Relation of Plasma Catecholamine Concentrations and Myocardial Mitochondrial Respiratory Activity in Anesthetized and Mechanically Ventilated, Cardiovascular Healthy Swine.

Chronic heart failure is associated with reduced myocardial β-adrenergic receptor expression and mitochondrial function. Since these data coincide with increased plasma catecholamine levels, we investigated the relation between myocardial β-receptor expression and mitochondrial respiratory activity under conditions of physiological catecholamine concentrations. This post hoc analysis used material of a prospective randomized, controlled study on 12 sexually mature (age 20-24 weeks) Early Life Stress or control pigs (weaning at day 21 and 28-35 after birth, respectively) of either sex. Measurements in anesthetized, mechanically ventilated, and instrumented animals comprised serum catecholamine (liquid-chromatography/tandem-mass-spectrometry) and 8-isoprostane levels, whole blood superoxide anion concentrations (electron spin resonance), oxidative DNA strand breaks (tail moment in the "comet assay"), post mortem cardiac tissue mitochondrial respiration, and immunohistochemistry (β2-adrenoreceptor, mitochondrial respiration complex, and nitrotyrosine expression). Catecholamine concentrations were inversely related to myocardial mitochondrial respiratory activity and β2-adrenoceptor expression, whereas there was no relation to mitochondrial respiratory complex expression. Except for a significant, direct, non-linear relation between DNA damage and noradrenaline levels, catecholamine concentrations were unrelated to markers of oxidative stress. The present study suggests that physiological variations of the plasma catecholamine concentrations, e.g., due to physical and/or psychological stress, may affect cardiac β2-adrenoceptor expression and mitochondrial respiration.

The effects of perioperative dexmedetomidine infusion on hemodynamic stability during laparoscopic adrenalectomy for pheochromocytoma: a randomized study.

Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumor originating from the adrenal medulla chromaffin cells. Hemodynamic instability can occur during the induction of anesthesia and surgical manipulation of the tumor. This study investigated the effects of intraoperative dexmedetomidine administration on hemodynamic stability in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. Forty patients who underwent laparoscopic adrenalectomy for pheochromocytoma were randomly assigned to the dexmedetomidine (n = 20) or control (n = 20) group. The primary outcome of this study was intraoperative hemodynamic stability, and the secondary endpoint was the plasma catecholamine concentrations, specifically of epinephrine and norepinephrine. The intraoperative maximum blood pressures were significantly lower in the dexmedetomidine group (control vs. dexmedetomidine group: 182 ± 31 vs. 161 ± 20, 102 ± 17 vs. 90 ± 10, and 128 ± 22 vs. 116 ± 12 [mean ± SD] mmHg and p = 0.020, 0.015, and 0.040 for systolic, diastolic, and mean blood pressure, respectively). The maximum heart rate during surgery was 108 ± 15 bpm in the control group and 95 ± 12 bpm in the dexmedetomidine group (p = 0.010). Other parameters of hemodynamic instability were comparable between both groups. Plasma catecholamine concentrations did not differ between the groups. Dexmedetomidine infusion following the induction of anesthesia at a rate of 0.5 μg/kg/h significantly attenuated the maximum intraoperative SBP, DBP, MBP, and HR, contributing to improved hemodynamic stability.

Abnormally high expression of D1-like dopamine receptors on lupus CD4+ T cells promotes Tfh cell differentiation

ObjectiveSLE is a chronic autoimmune disease that places a great burden on human society. T follicular helper (Tfh) cells play a critical role in the pathological process of SLE. Therefore,...

Efficiacy of Pharmacotherapy in Patients with Hypothimic Mental Disorders Suffered from Covid-19 Infection

IntroductionIn organic mental disorders in people who have undergone COVID-19, it has been established that the complex use of periciazine in combination with paroxetine, diazepam, 3-hydroxypyridine succinate and hyperbaric oxygenation is superior in effectiveness to traditional therapy with an antipsychotic drug, antidepressant and anxiolytic. The inclusion of 3-hydroxypyridine succinate, hyperbaric oxygenation in the complex therapy of this pathology corrects the concentrations of adrenaline, norepinephrine, dopamine, serotonin in the peripheral blood of patients, eliminates hormonal status disorders and humoral immune responses.ObjectivesThe aim of the work was to optimize approaches to the treatment of hypothymic disorders in organic mental illness, to substantiate the complex use of periciazine in combination with paroxetine, diazepam, 3-hydroxypyridine succinate and hyperbaric oxygenation in patients who underwent COVID-19.MethodsThe object of the clinical study were patients with organic mental disorders who underwent COVID-19. To assess the condition, laboratory research methods were selected taking into account the etio- and pathogenesis of diseases: determining the level of catecholamines, some indicators of humoral immune responses, and the hormonal profile.ResultsTable 2.3 - Nosological structure of patients included in the studyNosological formAssociated hypothymic disorder Number of patientsGender Average age (years)MalesFemalesOrganic mental disorderOrganic anxiety disorder F06.42115628,7±6,3Depressive Episode F3322129Organic mental disorder associated with COVID-19Organic anxiety disorder F06.418153Depressive Episode F331610643,7±7,4ConclusionsIn patients with organic mental disorders, occurring with hypothymic symptoms, compared with healthy donors, there is a complex of disorders in plasma concentrations of catecholamines. Traditional and, to a greater extent, combination therapy increase the levels of serotonin, dopamine, norepinephrine, both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.In patients with organic mental disorders, occurring with hypothymic symptoms, compared with healthy donors, there is a complex of disorders in plasma concentrations of catecholamines. Traditional and, to a greater extent, combination therapy increase the levels of serotonin, dopamine, norepinephrine, both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.Complex therapy with periciazine, paroxetine, diazepam in combination with 3-hydroxypyridine succinate and HBO for organic mental disorders causes a more complete reduction of hypothymic disorders both in the group of patients who did not have COVID-19, and in those who underwent a new coronovirus infection.Disclosure of InterestNone Declared

COMPARISON OF DEXMEDETOMIDINE VERSUS FENTANYL IN ATTENUATING PRESSOR RESPONSE DURING LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION

Background and objectives: Laryngoscopy and intubation is associated with a sympathetic response that results in a rapid increase in blood pressure and heart rate. The mechanisms underlying these hemodynamic changes are incompletely understood. They may be caused by a reex sympathetic discharge due to stimulation of the upper respiratory tract. It has been observed that hemodynamic responses to tracheal intubation are associated with an increase in plasma catecholamine concentrations and are attenuated by β-adrenergic blockade. This study was conducted to compare the efcacy of dexmedetomidine and fentanyl for attenuation of pressor response during laryngoscopy and intubation. Materials and methods Following approval by ethical committee, 60 ASA grade I and II patients of either sex undergoing general anaesthesia for elective surgery were included in this study. Patients were randomly divided into two groups of 30 patients each. Dexmedetomidine in a dose of 1μg/kg i.v was given to Group A patients and Fentanyl 2 μg/kg i.v was given to Group B patients. Both the drugs were diluted with normal saline solution to make 10ml and were administered slow intravenous 10 min before induction. The hemodynamic parameters were recorded, demographic data was analyzed using unpaired t-test and hemodynamic variables were analyzed by using unpaired and paired t-test. Side effects were analyzed using chi square test. Result: The two groups were comparable in their demographic proles. Dexmedetomidine proved itself to be an excellent drug when given intravenously in dose of 1μg/kg to attenuate hemodynamic response to laryngoscopy and intubation. It blunted the hemodynamic response to laryngoscopy and intubation to a greater magnitude than fentanyl in a dose of 2μg/kg intravenously as a premedication. Conclusion: We conclude that fentanyl 2μg/kg i.v. given ten minutes prior to airway instrumentation shows an inconsistent response to laryngoscopy and intubation. Between the two drugs under study, the use of dexmedetomidine 1μg/kg i.v. is satisfactory and produces a more favorable hemodynamic prole while fentanyl 2μg/kg is found to be non- dependable and less effective for the attenuation of the pressor response to laryngoscopy and endotracheal intubation.

Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension.

Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system. It produces and releases metanephrines, which are used as biomarkers for diagnosis in plasma and urine. However, plasma catecholamine concentrations remain generally normal in children with NB. Thus, unlike pheochromocytoma and paraganglioma (PHEO/PGL), two other non-epithelial neuroendocrine tumors, hypertension is not part of the usual clinical picture of patients with NB. This suggests that the mode of production and secretion of catecholamines and metanephrines in NB is different from that in PHEO/PGL, but little is known about these discrepancies. Here we aim to provide a detailed comparison of the biosynthesis, metabolism and storage of catecholamines and metanephrines between patients with NB and PHEO. Catecholamines and metanephrines were quantified in NB and PHEO/PGL patients from plasma and tumor tissues by ultra-high pressure liquid chromatography tandem mass spectrometry. Electron microscopy was used to quantify neurosecretory vesicles within cells derived from PHEO tumor biopsies, NB-PDX and NB cell lines. Chromaffin markers were detected by qPCR, IHC and/or immunoblotting. Plasma levels of metanephrines were comparable between NB and PHEO patients, while catecholamines were 3.5-fold lower in NB vs PHEO affected individuals. However, we observed that intratumoral concentrations of metanephrines and catecholamines measured in NB were several orders of magnitude lower than in PHEO. Cellular and molecular analyses revealed that NB cell lines, primary cells dissociated from human tumor biopsies as well as cells from patient-derived xenograft tumors (NB-PDX) stored a very low amount of intracellular catecholamines, and contained only rare neurosecretory vesicles relative to PHEO cells. In addition, primary NB expressed reduced levels of numerous chromaffin markers, as compared to PHEO/PGL, except catechol O-methyltransferase and monoamine oxidase A. Furthermore, functional assays through induction of chromaffin differentiation of the IMR32 NB cell line with Bt2cAMP led to an increase of neurosecretory vesicles able to secrete catecholamines after KCl or nicotine stimulation. The low amount of neurosecretory vesicles in NB cytoplasm prevents catecholamine storage and lead to their rapid transformation by catechol O-methyltransferase into metanephrines that diffuse in blood. Hence, in contrast to PHEO/PGL, catecholamines are not secreted massively in the blood, which explains why systemic hypertension is not observed in most patients with NB.

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

An Unusual Cause of Acidosis in a Man With Clostridium difficile Colitis

Low and Moderate Doses of Caffeinated Coffee Improve Repeated Sprint Performance in Female Team Sport Athletes.

Simple SummaryThe bulk of research on caffeine as an ergogenic aid has been on endurance performance, however there is evidence that caffeine can enhance short-term high-intensity performance. Caffeine may have an ergogenic impact during anaerobic exercise by facilitating central effects by antagonizing adenosine receptors, hence decreasing the detrimental effects of adenosine on neurotransmission, arousal, and pain perception. Caffeine intake also activates the central nervous system, which promotes alertness and concentration. Additionally, athletes typically consume coffee containing caffeine. To date, the bulk of study has focused on the administration of 3–9 mg/kg of anhydrous caffeine, as opposed to the readily accessible source of caffeine, coffee, and has mostly been conducted on males. Consequently, there is a dearth of study evaluating the ergogenic impact of caffeine on females, particularly when consuming alternative caffeine delivery methods, such as coffee. The current study is the first to investigate the effects of low (3 mg/kg) and moderate (6 mg/kg) doses of caffeine from coffee on repeated sprint performance in females.The aim of this study was to determine the effect of low and moderate doses of caffeine ingestion via caffeinated coffee on repeated sprint test (RST) and plasma catecholamine concentration in trained female team-sport athletes. In a randomized, double-blind, crossover design, 13 female team-sport athletes (VO2max: 48.7 ± 4 mL·kg·min−1) completed three RST trials, separated by 4-day, 60 min post-ingestion of either 3 mg·kg−1 (LCOF) or 6 mg·kg−1 (MCOF) or placebo (PLA). The RST consisted of 12 × 4 s sprints on a cycle ergometer interspersed with 20 s of active recovery. Blood lactate (BLa) and glucose (GLU) and epinephrine and norepinephrine concentrations were collected before and 60 min after coffee ingestion, and after RST. Heart rate (HR) and ratings of perceived exertion (RPE) were measured at the beginning of RST, and after the 6th and 12th sprints. Average peak power score during RST was significantly improved after LCOF (p = 0.016) and MCOF (p = 0.041) compared to PLA, but peak and mean power output of the individual sprints, and fatigue index were not different between trials (all p > 0.05). Epinephrine and norepinephrine concentrations were significantly higher before and after RST in LCOF and MCOF compared to PLA (all p < 0.05). BLa was also higher after RST in both LCOF and MCOF compared to PLA (p = 0.005). HR, RPE, and GLU were not different between conditions (p > 0.05). In conclusion, low and moderate dose of caffeine ingestion can enhance the average peak power score during repeated sprints. These findings partly support low and moderate doses of caffeine supplementation via coffee as a nutritional ergogenic aid for trained female team-sport players during repeated sprint exercise.

Improvement of several stress response and sleep quality hormones in men and women after sleeping in a bed that protects against electromagnetic fields

BackgroundThe electromagnetic fields (EMFs) emitted by the technologies affect the homeostatic systems (nervous, endocrine, and immune systems) and consequently the health. In a previous work, we observed that men and women, after 2 months of using a bed with a registered HOGO system, that prevents and drain EMFs, improved their immunity, redox and inflammatory states and rejuvenated their rate of aging or biological age. Since, EMFs can act as a chronic stressor stimulus, and affect the sleep quality. The objective of this work was to study in men and women (23–73 years old) the effect of sleeping for 2 months on that bed in the blood concentrations of several hormones related to stress response and sleep quality as well as to corroborate the rejuvenation of their biological age.MethodsIn 18 men and women, plasma concentration of cortisol, dehydroepiandrosterone (DHEA), catecholamines (epinephrine, norepinephrine and dopamine), serotonin, oxytocin and melatonin were analyzed before and after 2 months of using the HOGO beds. A group of 10 people was used as placebo control. In another cohort of 25 men (20 experimental and 5 placebo), the effects of rest on the HOGO system on the concentration of cortisol and testosterone in plasma were studied. In all these volunteers, the biological age was analyzed using the Immunity Clock model.ResultsThere is a significant increase in plasma concentration of DHEA, norepinephrine, serotonin, oxytocin, and melatonin as well as in testosterone, after resting for 2 months in that bed with the EMFs avoiding system. In addition, decreases in Cortisol/DHEA and Testosterone/cortisol ratio and plasma dopamine concentration were observed. No differences were found in placebo groups. In all participants that slept on HOGO beds, the biological age was reduced.ConclusionsSleeping in a bed that isolates from EMFs and drain them can be a possible strategy to improve the secretion of hormones related to a better response to stress and sleep quality, which means a better endocrine system, and consequently better homeostasis and maintenance of health. This fact was confirmed with the slowdown in the rate of aging checked with a rejuvenation of the biological age.

Fear Detection in Multimodal Affective Computing: Physiological Signals versus Catecholamine Concentration

Affective computing through physiological signals monitoring is currently a hot topic in the scientific literature, but also in the industry. Many wearable devices are being developed for health or wellness tracking during daily life or sports activity. Likewise, other applications are being proposed for the early detection of risk situations involving sexual or violent aggressions, with the identification of panic or fear emotions. The use of other sources of information, such as video or audio signals will make multimodal affective computing a more powerful tool for emotion classification, improving the detection capability. There are other biological elements that have not been explored yet and that could provide additional information to better disentangle negative emotions, such as fear or panic. Catecholamines are hormones produced by the adrenal glands, two small glands located above the kidneys. These hormones are released in the body in response to physical or emotional stress. The main catecholamines, namely adrenaline, noradrenaline and dopamine have been analysed, as well as four physiological variables: skin temperature, electrodermal activity, blood volume pulse (to calculate heart rate activity. i.e., beats per minute) and respiration rate. This work presents a comparison of the results provided by the analysis of physiological signals in reference to catecholamine, from an experimental task with 21 female volunteers receiving audiovisual stimuli through an immersive environment in virtual reality. Artificial intelligence algorithms for fear classification with physiological variables and plasma catecholamine concentration levels have been proposed and tested. The best results have been obtained with the features extracted from the physiological variables. Adding catecholamine’s maximum variation during the five minutes after the video clip visualization, as well as adding the five measurements (1-min interval) of these levels, are not providing better performance in the classifiers.

Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial.

Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: −41.5 ng·L−1, 95%CI −134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L−1, 95%CI −7.6, 30.1; p = 0.24), and dopamine (effect estimated: −1.61 ng·L−1, 95%CI −7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.

Use of Alpha 2 Agonist in Septic Shock: A Case Report

In this case study the aim is to highlight the role of Alpha-2 agonists to reduce vasopressor requirements in septic shock. In fact the case presented to us is an 11-month-old child admitted for burns on the whole body. The usual treatment does not seem to be very effective, so the hospital's medical team decided to inject him with a α 2-adrenoceptor agonists: Remarkable results have emerged at the end of this treatment. It has been proven that Clonidine reduces sympathetic nerve activity to the heart and vasculature by a direct central action, which is its main mechanism of action as an antihypertensive drug. With reductions in sympathetic nerve activity to other organs, this is likely associated with a decrease in plasma catecholamines concentrations. This substance has a special mechanism which has proven a succes in septic shock.

Effect of Labetalol-Fentanyl and Fentanyl alone for attenuating pressure responses to intubation and skull pin insertion in neurosurgery: A Comparative study

Background: Laryngoscopy and endotracheal intubation are noxious stimuli capable of producing a hugespectrum of stress responses such as tachycardia, hypertension, laryngospasm, bronchospasm, raisedintracranial pressure and intraocular pressure. Simultaneously skull pin insertion during neurosurgicaltechnique aggravates the noxious stimulus causing acute hypertension even in an adequately anaesthetizedpatient. These haemodynamic changes are generally temporary without any sequelae in normotensive patients,but can accelerate the development of complications, e.g., myocardial ischemia, arrhythmia, infarction andcerebral haemorrhagein patients with coronary artery disease, hypertension or cerebrovascular disease.Different pharmacological agents are used in order to prevent haemodynamic responses. Intravenous Fentanylhas showed a promising result, preventing the increase in plasma concentrations of catecholamines anddecreasing the central sympathetic outflow. Another agent labetalol, is an unique oral and parenteralantihypertensive drug that is α1 and nonselective β1 and β2 adrenergic antagonist. Objectives: To evaluate the effectiveness of Labetalol-fentanyl for attenuating pressure responses tointubation as well as skull pin insertion in patients undergoing neurosurgery under general anesthesia. Materials &amp; method: This prospective, randomized controlled trial was conducted Department ofAnaesthesia Analgesia and Intensive Care Medicine, Dhaka Medical College Hospital from 18th March 2019to 17thSeptember 2019. Total 60 patients undergone elective neurosurgery and requiring pin insertion wereenrolled for the study and allocated into two groups. Group A: patients given intravenous 0.25 mg/kgLabetalol and fentanyl 2μg/kg combination. Group B patients were given intravenous Fentanyl alone.Following that haemodynamic condition and outcome was assessed at different point of time. Result: Mean age was found to 45.8±11.5 years. It was observed that almost two third (63.3% &amp; 60.0%)patients had ASA grade I in group A and group B respectively. After induction, mean heart rate wasincreases in both group but more in group B. It was 92.4.7±7.8 beat/min and 97.3±7.4 beat/min in group Aand group B respectively. After pin insertion, mean heart rate was 84.1±5.4 beat/min in group A and98.5±85.4 beat/min in group B. after intubation MAP in group-B was statistically significant high(111.4±15.6 mmHg) as compared to group A (99.8±9.5 mmHg) and was unstable upto5 minute time. Thestatistically significant difference between groups was also observed at time of pin insertion (97.5±9.7 mmHgin group A vs. 110.6±12.9 mmHg in group B), after pin insertion (94.9±10.3 mmHg in group A vs. 111.5±10.4mmHg in group B). Intraoperative HR &amp; MAP were almost normal and and remained stabilized in group-Apatients. Conclusion:Labetalol-Fentanyl combination was more effective compared to Fentanyl alone in attenuatingthe pressure responses to intubation and skull pin insertion in neurosurgery. JBSA 2021; 34 (2) : 36-43

Renalase in Haemodialysis Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

Clinical Presentation and Treatment Outcomes of Children and Adolescents With Pheochromocytoma and Paraganglioma in a Single Center in Korea.

PurposePheochromocytoma (PCC) and paraganglioma (PGL) (PPGL) are rare neuroendocrine tumors, and data on managing these conditions in children and adolescents are lacking. The objective of this study was to demonstrate the clinical presentation and treatment outcomes in children and adolescents with PPGL in a single tertiary care center in Korea.MethodsThis retrospective study included 23 patients diagnosed with PCC (n = 14) and PGL (n = 9) before the age of 21 at Samsung Medical Center (from June 1994 to June 2019). We describe age, gender, family history, clinical characteristics, laboratory findings, pathologic findings, therapeutic approaches, and treatment outcomes.ResultsOf the 23 patients, 14 had PCC and nine had PGL. The median age at diagnosis was 16.8 years (range, 6.8–20.8 years). The common presenting symptoms were hypertension (n = 10), headache (n = 9), palpitation (n = 4), and sweating (n = 4). The plasma or 24-hour urine catecholamine and/or metabolite concentrations were markedly elevated in 22 patients with PPGL, but were normal in one patient with carotid body PGL. All tumors were visualized on computed tomography. Genetic tests were performed in 15 patients, and seven patients showed mutations in RET (n = 3), SDHB (n = 3), and VHL (n = 1). All patients underwent surgery, and complete excision was performed successfully. Three patients with metastasis underwent postoperative adjuvant therapy.ConclusionThis study suggests that pediatric PPGL tends to be extra-adrenal and bilateral and shows a higher potential for genetic mutations. Considering the hereditary predisposition of pediatric PPGL, genetic screening tests are strongly recommended, and lifelong follow-up is needed to detect recurrence and metastasis. Further research with a larger sample size and routine genetic screening is needed to better understand the genetic conditions and long-term prognosis of PPGL.

Diurnal versus Nocturnal Exercise-Effect on the Gastrointestinal Tract.

The study aimed to determine the effect of diurnal versus nocturnal exercise on gastrointestinal integrity and functional responses, plasma lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) concentrations (as indirect indicators of endotoxin responses), systemic inflammatory cytokine profile, gastrointestinal symptoms, and feeding tolerance. Endurance runners (n = 16) completed 3 h of 60% V˙O2max (22.7°C, 45% relative humidity) running, on one occasion performed at 0900 h (400 lx; DAY) and on another occasion at 2100 h (2 lx; NIGHT). Blood samples were collected pre- and postexercise and during recovery to determine plasma concentrations of cortisol, catecholamines, claudin-3, I-FABP, LBP, and sCD14 and inflammatory cytokine profiles by ELISA. Orocecal transit time (OCTT) was determined by lactulose challenge test given at 150 min, with concomitant breath hydrogen (H2) and gastrointestinal symptom determination. Cortisol increased substantially pre- to postexercise on NIGHT (+182%) versus DAY (+4%) (trial-time, P = 0.046), with no epinephrine (+41%) and norepinephrine (+102%) trial differences. I-FABP, but not claudin-3, increased pre- to postexercise on both trials (mean = 2269 pg·mL-1, 95% confidence interval = 1351-3187, +143%) (main effect of time [MEOT], P < 0.001). sCD14 increased pre- to postexercise (trial-time, P = 0.045, +5.6%) and was greater on DAY, but LBP decreased (MEOT, P = 0.019, -11.2%) on both trials. No trial difference was observed for systemic cytokine profile (MEOT, P = 0.004). Breath H2 responses (P = 0.019) showed that OCTT was significantly delayed on NIGHT (>84 min, with n = 3 showing no breath H2 turning point by 180 min postexercise) compared with DAY (mean = 54 min, 95% confidence interval = 29-79). NIGHT resulted in greater total gastrointestinal symptoms (P = 0.009) compared with DAY. No difference in feeding tolerance markers was observed between trials. Nocturnal exercise instigates greater gastrointestinal functional perturbations and symptoms compared with diurnal exercise. However, there are no circadian differences to gastrointestinal integrity and systemic perturbations in response to the same exertional stress and controlled procedures.

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

What is the central question of this study? The acute hypoxic compensatory reaction is based on haemodynamic changes, and β-adrenoceptors are involved in haemodynamic regulation. What is the role of β-adrenoceptors in haemodynamics during hypoxic exposure? What is the main finding and its importance? Activation of β2 -adrenoceptors attenuates the increase in pulmonary artery pressure during hypoxic exposure. This compensatory reaction activated by β2 -adrenoceptors during hypoxic stress is very important to maintain the activities of normal life. The acute hypoxic compensatory reaction is accompanied by haemodynamic changes. We monitored the haemodynamic changes in rats undergoing acute hypoxic stress and applied antagonists of β-adrenoceptor (β-ARs) subtypes to reveal the regulatory role of β-ARs on haemodynamics. Sprague-Dawley rats were randomly divided into control, atenolol (β1 -AR antagonist), ICI118,551 (β2 -AR antagonist) and propranolol (non-selective β-AR antagonist) groups. Rats were continuously recorded for changes in haemodynamic indexes for 10min after administration. Then, a hypoxic ventilation experiment [15% O2 , 2200 m a.sl., 582 mmHg (0.765 Pa), 87.3 mmHg; Xining, China] was conducted, and the indexes were monitored for 5min after induction of hypoxia. Plasma catecholamine concentrations were also measured. We found that, during normoxia, the mean arterial pressure, heart rate, ascending aortic blood flow and pulmonary artery pressure were reduced in the propranolol and atenolol groups. Catecholamine concentrations were increased significantly in the atenolol group compared with the control group. During hypoxia, mean arterial pressure and total peripheral resistance were decreased in the control, propranolol and ICI118,551 groups. Pulmonary arterial pressure and pulmonary vascular resistance were increased in the propranolol and ICI118,551 groups. During hypoxia, catecholamine concentrations were increased significantly in the control group, but decreased in β-AR antagonist groups. In conclusion, the β2 -AR is involved in regulation of pulmonary haemodynamics in the acute hypoxic compensatory reaction, and the activation of β2 -ARs attenuates the increase in pulmonary arterial pressure during hypoxic stress. This compensatory reaction activated by β2 -ARs during hypoxic stress is very important to maintain activities of normal life.