Epinephrine Concentrations Research Articles

Electrochemical determination of epinephrine based on Ti3C2Tx MXene-reduced graphene oxide/ITO electrode

EP is an important natural catecholamine neurotransmitter in the central nervous system, and the change of EP concentration will lead to many diseases. Therefore, rapid and sensitive detection of EP is of great significance for clinical research. The Ti3C2Tx MXene dispersion obtained by in-situ HF etching Ti3AlC2 was mixed with graphene oxide (GO) dispersion synthesized by the modified Hummers method. After freeze drying and heat-treatment, the reduced graphene oxide/Ti3C2Tx MXene (GMA) was obtained and then the GMA was moved onto indium tin oxide (ITO) as the GMA/ITO working electrode for electrochemical detection of epinephrine (EP). The results are as follows: Ti3C2Tx MXene with a diameter of approximately 150 nm is uniformly distributed on the surface of the 3D graphene. The three-dimensional structure of GMA facilitates the entry of bioactive molecules and increases the contact area. GMA/ITO has a high sensitivity for the determination of EP 3.74 μA·μM−1·cm−2. Moreover, the electrode shows a very low detection limit, well repeatability and stability, and it can detect the EP content in real urine samples.

Influence of nitisinone and its metabolites on l-tyrosine metabolism in a model system

Nitisinone (NTBC) is currently used for the treatment of tyrosinemia type 1, a rare disease. It also exhibits potential in the treatment of other orphan diseases as well as nervous system disorders – this is however limited by its side effects. In all living organisms, NTBC inhibits 4-hydroxyphenylpyruvate dioxygenase activity, thereby affecting l-tyrosine (L-TYR) catabolism, which results in the therapeutic effect. The NTBC metabolites formed in patient's body is one of the causes of its side effects. The influence of NTBC and its metabolites; 2-amino-4-(trifluoromethyl)benzoic acid, 2-nitro-4-(trifluoromethyl)benzoic acid, and cyclohexane-1,3-dione on L-TYR catabolism was investigated in Raphanus sativus var. longipinnatus. Based on targeted LC–MS/MS analysis the concentration of NTBC and its metabolites in exposed plant tissues was determined. Based on non-targeted LC-MS/MS analysis the concentrations of products of L-TYR catabolism: levodopa, epinephrine, norepinephrine, normetanephrine, dopamine, tyramine and vitamins C, B5 and B6, additionally leucine and valine were identified as influenced by the NTBC or its metabolites.NTBC and its metabolites influenced L-TYR catabolism differently. Particularly significant changes were found in the content of epinephrine and normetanephrine: in the plant tissues exposed to NTBC, an increase in the content of these neurotransmitters was found (+42%), whereas in the plant treated with 2-amino-4-(trifluoromethyl)benzoic acid or 2-nitro-4-(trifluoromethyl)benzoic acid a decrease in concentration (−39% and 55%, respectively) was observed. Cyclohexane-1,3-dione does not influence epinephrine and normetanephrine concentration. The conclusions of this study provide a platform for expanded research on the causes of side effects of NTBC treatment.

Changes in parameters of biochemical and oxidative stress in university students during and after examinations.

The study aimed to evaluate the parameters of lipid peroxidation and antioxidant protection, biochemical parameters, and cortisol and adrenaline content in the blood of students depending on the effect of exam stress. A total of 135 healthy students (72 female (53.3%) and 63 male (46.7%)) aged from 19 to 21 years (mean age 20.16 ± 0.42 years) of the experimental group underwent detailed medical screening and examination before the inclusion in the study. The control group consisted of 30 healthy students (17 female (56.7%) and 13 male (43.3%)) of corresponding age (mean age 20.23 ± 0.54 years), whose medical examination was performed during breaks in the absence of any stress factors. The blood parameters of the experimental group were investigated 1 h before, 1 h after, and 24 h after the exam. The cortisol content in the blood of experimental group students significantly increased 1.37 times (p < 0.05) an hour before the exam and 1.32 times (p < 0.05) an hour after; adrenalin content in blood increased 1.76 times (p < 0.05) and 1.49 times (p < 0.05), respectively. Compared to the control group, intensification of lipid peroxidation processes with a 1.51-fold (p < 0.05) increase in erythrocyte malonic aldehyde content in blood 1 h before and 1.42-fold (p < 0.05) increase an hour after the exam was observed in students due to the effect of exam stress.. Changes in hormonal homeostasis, activation of lipoperoxidation processes with the development of oxidative stress, and the disintegration of antioxidant protection factors are typical for academic stress in students.

Characteristics and physiological basis of falls in ventricular outputs after immediate cord clamping at delivery in preterm fetal lambs.

Controversy exists about the physiological mechanism(s) underlying decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, the four major determinants of ventricular output (afterload, preload, heart rate and contractility) were measured concurrently in fetal lambs at 15s intervals over a 2min period after cord clamping and before ventilation following delivery. After cord clamping, right (but not left) ventricular output fell by 20% in the initial 30s, due to increased afterload associated with higher arterial blood pressures, but both outputs then halved over 45s, due to a falling heart rate and deteriorating ventricular contractility accompanying rapid declines in arterial oxygenation to asphyxial levels. Ventricular outputs subsequently plateaued from 75 to 120s, associated with rebound rises in ventricular contractility accompanying asphyxia-induced surges in circulating catecholamines. These findings provide a physiological basis for the clinical recommendation that effective ventilation should occur within 60s after immediate cord clamping. Controversy exists about the physiological mechanism(s) underlying large decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, anaesthetized preterm fetal lambs (127(1)d, n=12) were instrumented with flow probes and catheters in major central arteries, and a left ventricular (LV) micromanometer-conductance catheter. Following immediate cord clamping at delivery, haemodynamics, LV and right ventricular (RV) outputs, and LV contractility were measured at 15s intervals during a 2min non-ventilatory period, with aortic blood gases and circulating catecholamine (noradrenaline and adrenaline) concentrations measured at 30s intervals. After cord clamping, (1) RV (but not LV) output fell by 20% in the initial 30s, due to a reduced stroke volume associated with increased arterial blood pressures, (2) both outputs then halved over the next 45s, associated with falls in heart rate, arterial blood pressures and ventricular contractility accompanying a rapid decline in arterial oxygenation to asphyxial levels, (3) reduced outputs subsequently plateaued from 75 to 120s, associated with rebound rises in blood pressures and ventricular contractility accompanying exponential surges in circulating catecholamines. These findings are consistent with a time-dependent decline of ventricular outputs after immediate cord clamping, which comprised (1) an initial, minor fall in RV output related to altered loading conditions, (2) ensuing large decreases in both LV and RV outputs related to the combination of bradycardia and ventricular dysfunction during emergence of an asphyxial state, and (3) subsequent stabilization of reduced LV and RV outputs during ongoing asphyxia, supported by cardiovascular stimulatory effects of marked sympathoadrenal activation.

Alpha and beta adrenergic receptors modulate keratinocyte migration.

Keratinocyte migration into skin wounds is the step of the healing process that correlates with the wound closure rate. Keratinocyte migration, and wound epithelialization are decreased when beta 2-adrenergic receptors (B2AR) are activated by 1 μM epinephrine/adrenaline, resulting in delayed wound healing in human and mouse skin. In the present study, we found paradoxically, that in a subset of keratinocyte strains exposure to low concentrations of epinephrine (0.1 nM) increased, rather than decreased, their migratory rate. We find that both the alpha- and the beta-adrenergic receptors are expressed in human keratinocytes, and expression of alpha-2 AR subtypes demonstrated for the first time. Therefore, we tested if the alpha-AR could be modulating the increased migratory response observed in these cell strains. By using specific inhibitors to alpha-AR, we demonstrated that blocking A2B-AR could reverse the rapid cell migration induced by the 0.1 nM epinephrine. Phosphorylation of ERK was elevated after 1–10 minutes of the low epinephrine treatment and the A2B-AR inhibitor blocked the ERK phosphorylation. The results suggest that both the A2B-AR and B2AR mediate keratinocyte migration, in which with a low level of epinephrine treatment, A2B-AR could alter the B2AR signals and regulate the migration rate.

The Effects of Furosemide on Behavioral and Hormonal Parameters in Male and Female Mice Subjected to Immobilization and Cold-Water Stress.

IntroductionThe diuretic agent furosemide (FUR, 25 and 50 mg/kg) has been shown in a single report to act as an anti-stressor agent in two models of acute stress in mice, viz. electric foot–shock stress and immobilization (IMS). The present work aimed to investigate the possible anti-stressor action of FUR on two models of acute stress in mice, cold-water stress (CWS) and IMS, and tried to determine whether gender has any impact on the effect of FUR.MethodsFUR (40 mg/kg) was injected intraperitoneally, and after 30 minutes, mice were subjected to CWS (4°C for three minutes) or IMS (fixing movement for two and a half hrs using adhesive tape). Motor and exploratory activities, neuromuscular coordination, and thermal nociception were then tested. Blood was collected from the mice and used to measure the concentrations of three stress hormones (corticosterone, epinephrine and prolactin).ResultsMice subjected to CWS and IMS had significantly reduced motor and exploratory activities, neuromuscular coordination, and increased nociception. CWS and IMS also significantly increased the plasma concentrations of the three hormones. FUR pretreatment significantly mitigated these stress-induced hormonal changes. There was no significant sex difference when CWS or IMS was applied.DiscussionIMS and CWS stimuli in male and female mice caused significant elevations in the plasma concentrations of corticosterone, epinephrine, and prolactin, accompanied by a significant reduction of motor and exploratory activities, neuromuscular coordination, and thermal nociception. There were no sex differences when IMS was applied. In stressed mice, prior administration of FUR (40 mg/kg) significantly decreased the concentrations of stress hormones, and this effect significantly mitigated the stress-induced behavioural and motor changes.

IMMUNOLOGICAL ASSESSMENT OF THE STRESS RESPONSE IN PATIENTS WITH INFLAMMATORY POSTPROTHETIC COMPLICATIONS

Post-prosthetic complications during dental implantation are accompanied by pain symptoms leading to disorders of the psychoemotional state. All this influences the behavior of patients. In addition, psychoemotional stress is often a factor of provocation and persistence of the complications. The presence of a stress state in the identified pathology, as well as the influence of various therapies on the treatment of post-prosthetic complications, is reflected in the dynamics of changes in the concentrations of both catecholamines (epinephrine, norepinephrine) and glucocorticoids (cortisol) — hormones of the medulla and the adrenal cortex. The aim: to conduct an immunological analysis of the stress response in patients with postprosthetic complications during dental implantation. Materials and methods: The study was performed in 120 patients with post-prosthetic complications during dental implantation before and during treatment: Group I (control) — 30 patients treated with the conventional therapy; group II — 30 patients treated with ozone therapy in addition to the conventional therapy; group III — 30 patients treated with transcranial electrical stimulation in addition to the conventional therapy; Group IV — 30 patients treated with a combination of conventional therapy, ozone therapy and transcranial electrical stimulation. The concentration of epinephrine, norepinephrine, cortisol, alkaline phosphatase, and the Garkavi index were evaluated. Results: The change in these indicators after the treatment indicates the normalization of the level of the studied enzymes — markers of bone homeostasis, which is confirmed by an improvement in the clinical picture in the oral cavity. Conclusion: changes in immunological parameters objectively reflect the psychoemotional state of patients. The nature of changes in the hormonal stress response to the treatment of post-prosthetic complications indicates the effectiveness of the therapeutic regimens used, and, as a result, a decrease in both pain symptoms and psychoemotional stress.

Brain-Derived Neurotrophic Factor Induces Platelet Aggregation

Background: A large extra-cerebral pool of Brain-Derived Neurotrophic Factor (BDNF) is found in platelets. With concentrations reaching 100-1000 fold those of neurons, platelet-stored BDNF is hypothesized to play an important role in the vasculature.Aims: To investigate the effect of BDNF on platelets, alone and synergistically with traditional agonists.Methods: The presence of BDNF in platelets was confirmed by Western Blotting and confocal microscopy. The ability of platelets to release BDNF upon stimulation was assessed by ELISA on platelet releasates following stimulation by maximal concentrations of arachidonic acid, adenosine diphosphate (ADP), epinephrine, collagen, or thrombin-receptor activating peptide (TRAP). To investigate the effect of BDNF on platelet function, we used a recombinant BDNF protein (rBDNF, Peprotech) added exogenously to a preparation of washed platelets obtained from healthy volunteers. Aggregation was recorded by light transmission aggregometry over 20 minutes. Synergistic assays were used with priming (sub-threshold) concentrations of either collagen or TRAP. The dependence on secondary mediators was assessed by blocking either COX-1-dependent thromboxane formation with aspirin or the ADP-P2Y12 receptor with AR-C66096. Platelet aggregation was blocked with a GPIIbIIIa inhibitor (abciximab) to assess the contribution of outside-in signalling.Results: Western blotting showed a 14kD band for the washed platelet protein preparations and for rBDNF used as a positive control. BDNF appeared stored in granules on confocal microscopy, consistent with previous reports. BDNF in the platelet releasate was increased 5-fold following platelet aggregation induced by traditional agonists, as compared with baseline. Exogenous rBDNF had no effect on platelet aggregation at low doses (1 and 3 µg/ml), but induced complete biphasic platelet aggregation at a high dose (10 µg/ml). The secondary wave of platelet aggregation was abrogated in the presence of aspirin and AR-C66096, but they had no effect on the primary wave. Platelet aggregation was completely abolished in the presence of the GPIIbIIIa inhibitor abciximab. Synergistic studies were conducted with priming concentrations of rBDNF, collagen and TRAP which were insufficient to elicit platelet aggregation on their own. Incubation of platelets with rBDNF (3 µg/ml) potentiated the platelet responses to priming concentrations of both collagen and TRAP. Indeed, in the absence of BDNF, no platelet aggregation was seen at the concentrations used, whereas incubation with BDNF led to complete and irreversible platelet aggregation to priming concentrations of collagen and TRAP.Conclusion: Platelets contain BDNF within their granules, which they release upon platelet activation with traditional agonists. Stimulation of washed platelets with high concentrations of rBDNF induced platelets to aggregate; in the presence of low concentrations of rBDNF, platelet aggregation was potentiated in response to priming concentrations of traditional agonists. Platelet responses to rBDNF were partly dependent on secondary mediators, as inhibition of COX-1 and the ADP-P2Y12 receptor inhibited the secondary wave of aggregation. However, the primary wave of aggregation was unaltered, thereby suggesting that platelets either possess a BDNF receptor or a traditional receptor that can signal in the presence of BDNF. Further studies are needed to uncover which receptor is implicated in platelet responses to BDNF, and the physiological role of BDNF-induced platelet responses. DisclosuresNo relevant conflicts of interest to declare.

Incidence of the "Adrenaline Rush" and Vasovagal Response with Local Anesthetic Injection.

Background:Many patients feel an “adrenaline rush” or a vasovagal reaction when injected with lidocaine and epinephrine during wide awake surgery. The incidence of these reactions is not well documented in the literature.Methods:In total, 387 patients were prospectively injected with lidocaine and epinephrine for minor procedures without sedation between July 1, 2019 and November 1, 2020. A concentration of epinephrine with 1:100,000 in 2% lidocaine was injected, with most patients getting less than 20 mL of volume.Results:Eight (2.2%) of the patients had adrenaline rush symptoms, which included nervousness, anxiety, tremors, shaky feelings, flushing, diaphoresis, light-headedness, tingling, and “heart racing.” Seven patients (1.8%) experienced vasovagal responses, which included nausea, a feeling of being unwell, faint, or lightheaded, or had circumoral pallor.Conclusions:Patients run a low risk of feeling an adrenaline rush or vasovagal reaction when injected with lidocaine and epinephrine. Routinely advising patients that the adrenaline rush can happen, and that this is not an allergic reaction can be helpful to allay fear of the unknown and to prevent false allergy beliefs. Injecting patients lying down may decrease the incidence of vasovagal reactions by increasing cerebral blood flow with the advantage of gravity.

Does the effect of adrenaline on intraoral 2% lidocaine contribute to haemodynamic instability?: A prospective, randomized double blinded study

AbstractAimEvaluation of the cardiac status and cardiovascular changes in hypertensive patients during minor oral surgical procedures injected with 2% lignocaine with 1:80,000 and 1:200,000 adrenaline.Materials and methodsA prospective, randomized, double‐blinded study compares and analyses the cardiovascular changes by monitoring vital signs, electrocardiogram and oxygen saturation, and the pain gradient of known cardiac patients treated with one or more hypertensive drugs. The efficacy and safety of two concentrations of adrenaline in 2% lidocaine in minor oral surgical procedures are evaluated.ResultsTwo percent of lignocaine with 1:80,000 adrenaline causes more haemodynamic changes than local anaesthetic (LA) with 1:200,000 adrenaline in patients with controlled hypertension.ConclusionTwo percent lignocaine with 1:80,000 adrenaline has no significant advantage over 2% lignocaine with 1:200,000 adrenaline for minor oral surgical procedures within the 30‐min duration. LA with 1:200,000 concentration of adrenaline provides similar quality of anaesthesia to 1:80,000 adrenaline concentration of the LA drug.

The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients.

Background/Aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Pancreatic Islets Exhibit Dysregulated Adaptation of Insulin Secretion after Chronic Epinephrine Exposure.

Chronic adrenergic stimulation is the dominant factor in impairment of the β-cell function. Sustained adrenergic exposure generates dysregulated insulin secretion in fetal sheep. Similar results have been shown in Min6 under the elevated epinephrine condition, but impairments after adrenergic removal are still unknown and a high rate of proliferation in Min6 has been ignored. Therefore, we incubated primary rats’ islets with half maximal inhibitory concentrations of epinephrine for three days, then determined their insulin secretion responsiveness and related signals two days after removal of adrenaline via radioimmunoassay and qPCR. Insulin secretion was not different between the exposure group (1.07 ± 0.04 ng/islet/h) and control (1.23 ± 0.17 ng/islet/h), but total islet insulin content after treatment (5.46 ± 0.87 ng/islet/h) was higher than control (3.17 ± 0.22 ng/islet/h, p < 0.05), and the fractional insulin release was 36% (p < 0.05) lower after the treatment. Meanwhile, the mRNA expression of Gαs, Gαz and Gβ1-2 decreased by 42.8% 19.4% and 24.8%, respectively (p < 0.05). Uncoupling protein 2 (Ucp2), sulphonylurea receptor 1 (Sur1) and superoxide dismutase 2 (Sod2) were significantly reduced (38.5%, 23.8% and 53.8%, p < 0.05). Chronic adrenergic exposure could impair insulin responsiveness in primary pancreatic islets. Decreased G proteins and Sur1 expression affect the regulation of insulin secretion. In conclusion, the sustained under-expression of Ucp2 and Sod2 may further change the function of β-cell, which helps to understand the long-term adrenergic adaptation of pancreatic β-cell.

Synthesis of porous 2D layered nickel oxide-reduced graphene oxide (NiO-rGO) hybrid composite for the efficient electrochemical detection of epinephrine in biological fluid

In the present research work, 2D-Porous NiO decorated graphene nanocomposite was synthesized by hydrothermal method to monitored the concentration of epinephrine (EPI). The morphology (SEM and TEM) results confirmed 2D-Porous NiO nanoparticles firmly attached over graphene nanosheets. FTIR and XPS analysis confirmed the formation of nickel oxide formation and complete reduction of GO to rGO. The electrochemical activity of the proposed NiO-rGO/GCE modified electrode on epinephrine was analyzed by simple cyclic voltammetry technique. The proposed low cost NiO-rGO/GCE modified electrode showed excellent catalytic activity over GCE and rGO/GCE electrodes. Due to its high conductivity and charge transfer ability of the NiO-rGO/GCE modified electrode exhibited high sensitivity of EPI at optimized conditions. The anodic peak current of the EPI linearly increases with increasing the concertation of EPI. A wide linear range (50 μM–1000 μM) was achieved with high correlation coefficient (R2 = 0.9986) and the limit of detection (LOD) of NiO-rGO/GCE modified electrode was calculated to be 10 μM. NiO-rGO/GCE electrode showed good stability and repeatability towards the EPI oxidation. Mainly, the proposed NiO-rGO/GCE modified electrode showed good sensitivity of EPI in the human biological fluid with high recovery percentage. The low cost, NiO-rGO/GCE electrode could be the promising sensor electrode for the detection of Epinephrine in the real samples.

Effect of intravenous oxycodone on the physiologic responses to extubation following general anesthesia

BackgroundEndotracheal intubation and extubation may cause undesirable hemodynamic changes. Intravenous oxycodone has recently been introduced and used for relieving hemodynamic alterations in response to intubation, but there is insufficient information regarding its application in stabilizing hemodynamics during extubation in the patients emerging from general anesthesia.MethodsOne hundred patients, who had undergone assorted laparoscopic surgeries under general anesthesia, were randomly assigned to Control group (saline injection, 50 cases) and Study group (intravenous injection of 0.08 mg/kg oxycodone immediately after completion of the surgical procedure, 50 cases). Blood pressure, heart rate, blood oxygen saturation (SpO2) as well as blood concentrations of epinephrine, norepinephrine, and cortisol were recorded or measured immediately before extubation (T0), during extubation (T1), as well as one minute (T2), 5 min (T3), and 10 min after extubation (T4). In addition, coughing and restlessness, time of eye-opening, and duration from completing surgery to extubation as well as Ramsay Sedation Scale were analyzed.ResultsBlood pressure and heart rate as well as blood concentrations of epinephrine, norepinephrine, and cortisol were significantly higher in the Control group compared with the Study group at the time of extubation as well as 1, 5, and 10 min after extubation (P < 0.05). When the patients emerged from general anesthesia, 70 % of the Control group had cough, which was significantly higher than that of Study group (40 %, P < 0.05). Significantly higher number of patients manifested restlessness in the Control group before (40 %) and after extubation (20 %) compared with that in the Study group (20 and 2 %, respectively, P < 0.05). In addition, patients of Control group had lower Ramsay score at extubation (1.7 ± 0.7) as well as 30 min after extubation (2.4 ± 0.9) compared to that of the patients of Study group (2.2 ± 0.9, and 3.0 ± 0.8, respectively, P = 0.003 and 0.001).ConclusionsIntravenous oxycodone attenuated alterations of hemodynamics and blood hormones associated with extubation during emergence from general anesthesia.Trial registrationChinese Clinical Trial Registry: ChiCTR2000040370 (registration date: 11-28-2020) “‘retrospectively registered”.

Platelet aggregation in patients with chronic heart failure in a "vortex" flow

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Исследование выполнено в рамках фундаментальной темы НИИ кардиологии АААА-А15-115123110026-3. Platelet aggregation mechanisms are studied using standard methods without taking turbulence into account. However, in cardiovascular diseases, the blood rheology changes, and the parameters of the turbulent flow acquire strong prothrombotic effects. The adhesion of several platelets creates a "snowball" effect with platelet hyperaggregation, leading to rapid vessel occlusion. Thus, the study of platelet aggregation in patients with cardiovascular diseases in conditions of creating a "vortex" flow in platelet-rich plasma is very relevant. Objective to study the effect of "vortex" flow in platelet-rich plasma on spontaneous and epinephrine-induced platelet aggregation in patients with CHF. Material and method. We studied 15 patients (75% of them men) with CHD, having CHF I-III FC. Platelet aggregation activity was studied using a turbidimetric method using a laser analyzer (220 LA "NPF Biola", Russia). Platelet aggregation activity in platelet-rich plasma (BTP) was estimated by light transmission curves in % and average aggregate size in relative units (Rel. units), with the inducer epinephrine in concentrations of 2 and 10 mg/ml, with constant stirring at 800 rpm. The same parameters were evaluated byour ownproposed approach with a creation ofa "vortex" plasma flow, which were achieved by changing the mixing rate of BTP from 0 to 800 rpm. Aggregation data is presented as a median with an interquartile range (Me (Q1; Q3)). Statistical data processing was performed using SPSS packages (version 19). The differences were considered significant at a significance level of p &amp;lt; 0.05. Results. In patients with CHF, the indicators of spontaneous aggregation measured by the standard method were 3.1 (1.5; 4.0) % and 1.7 (1.1; 2.0) Rel. units. Under the conditions of a"vortex" flow, the aggregate size increased to 5.4 (3.2; 6.1) Rel. units(p = 0.04). The indicators of standard epinephrine-induced aggregation at a concentration of 2 mg/ml were 46.7 (35.8; 66.2) % and 15.0(11.4; 18.9) Rel. units, and when the mixing speed was changed from 0 to 800 rpm, the indicators increased to 52.7 (41.3; 76.5) % (p = 0.003) and 19.4 (17.3; 20.6) Rel. units(p = 0.04). In conditions of increased epinephrine concentration of 10 mg/ml, the indicators were 52.5 (41.9; 74.5) % (p = 0.03) and 15.8 (12.2; 18.4) Rel. units. Under the conditions of"vortex" flow, aggregation indicators were 75.4 (62.0; 80.5)% (p = 0.04), and the size of aggregates increased to 356.0 (230.5; 462.5) Rel. units. Conclusion. Standard methods for studying of platelet aggregation are not always sufficient to detect an increased pro-aggregative potential of platelets. The proposed method for creationof "vortex" flow conditions showed an increase in the size of platelet aggregates and the degree of aggregation against the background of increased epinephrine concentration in patients with chronic heart failure, which proves its effectiveness in detecting platelet hyperaggregation.

Maternal haemodynamics during labour epidural analgesia with and without adrenaline.

Labour is one of the most painful experiences in a woman's life. Epidural analgesia using low-concentration local anaesthetics and lipophilic opioids is the gold standard for pain relief during labour. Pregnancy in general, particularly labour, is associated with changes in maternal haemodynamic variables, such as cardiac output and heart rate, which increase and peak during uterine contractions. Adrenaline is added to labour epidural solutions to enhance efficacy by stimulating the α2-adrenoreceptor. The minimal effective concentration of adrenaline was found to be 2μgmL-1 for postoperative analgesia. The addition of adrenaline may also produce vasoconstriction, limiting the absorption of fentanyl into the systemic circulation, thereby reducing foetal exposure. However, adrenaline may influence the haemodynamic fluctuations, possibly adding to the strain on the circulatory system. The aim of this study was to compare the haemodynamic changes after application of labour epidural analgesia with or without adrenaline 2μgmL-1. This was a secondary analysis of a single-centre, randomised double-blind trial. Forty-one nulliparous women in labour requesting epidural analgesia were randomised to receive epidural solution of bupivacaine 1mgmL-1, fentanyl 2μgmL-1 with or without adrenaline 2μgmL-1. The participants were monitored using a Nexfin CC continuous non-invasive blood pressure and cardiac output monitor. The primary outcomes were changes in peak systolic blood pressure and cardiac output during uterine contraction within 30min after epidural activation. The effect of adrenaline was tested statistically using a linear mixed-effects model of the outcome variables' dependency on time, adrenaline, and their interaction. After excluding three patients due to poor data quality and two due to a malfunctioning epidural catheter, 36 patients (18 in each group) were analysed. The addition of adrenaline to the solution had no significant effect on the temporal changes in peak systolic blood pressure (p=0.26), peak cardiac output (0.84), or heart rate (p=0.91). Furthermore, no significant temporal changes in maternal haemodynamics (peak systolic blood pressure, p=0.54, peak cardiac output, p=0.59, or heart rate p=0.55) were associated with epidural analgesia during 30min after epidural activation in both groups despite good analgesia. The addition of 2μgmL-1 adrenaline to the epidural solution is not likely to change maternal haemodynamics during labour.

Adrenaline May Contribute to Prothrombotic Condition via Augmentation of Platelet Procoagulant Response, Enhancement of Fibrin Formation, and Attenuation of Fibrinolysis.

Background: Adrenaline is believed to play a role in thrombosis and hemostasis. The complex effect of its clinically relevant concentrations on thrombus formation, coagulation and fibrinolysis in human blood has never been specifically studied.Methods: Confocal microscopy was used to study thrombus formation under flow, exposure of phosphatidylserine (PS) in adhered platelets, to evaluate clots density, and to measure kinetics of fibrin formation and external fibrinolysis under flow. Flow cytometry was utilized to assess PS exposure in non-adhered platelets. Kinetics of clot formation and internal fibrinolysis was evaluated by thromboelastometry. Platelet aggregation was measured by optical aggremometry. Kinetics of clot retraction was assessed by using digital camera.Results: We found that adrenaline (1–10 nM) is able to enhance platelet activation evoked by subthreshold collagen (150 ng/ml), resulting in augmentation of platelet aggregation, thrombus formation under arterial flow conditions, platelet PS exposure, and formation of platelet-fibrin clots. The development of platelet procoagulant response evoked by adrenaline + low collagen was associated with the formation of denser platelet-fibrin clots and the decrease in rate of fibrinolysis despite whether lysis was initiated inside (internal fibrinolysis) or outside the clot (external fibrinolysis). The above phenomena were abolished by the α2-adrenergic receptor antagonist, rauwolscine. Adrenaline-collagen synergism, expressed as PS exposure, was significantly reduced by cyclooxygenase inhibitor (acetylsalicic acid), GPIIb/IIIa receptor blocker (tirofiban), and P2Y12 receptor antagonist (PSB 0739).Conclusion: Clinically relevant concentrations of adrenaline may significantly augment responses of human platelets in the presence of subthreshold concentrations of collagen, which should be considered during therapies involving adrenaline infusion. Routinely used antiplatelet drugs may reduce the prothrombotic state evoked by adrenaline-collagen synergism.

Effects of L-3,4-dihydroxyphenylalanine (L-Dopa) Treatment in the Neuroendocrine Response to Stress

Stressful stimuli evoke a complex response mediated by two systems: the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Among the factors involved in stress, glucocorticoids and catecholamines secreted from the adrenal glands and sympathetic nerves are the main effectors of the physiological adaptations to stressors. Besides these, prolactin (PRL) is another hormone secreted under stress conditions. Catecholamines are synthesized from the hydroxylated precursor L-Dopa. This agent is commonly used for the treatment of Parkinson’s disease and it would act as a neurotransmitter per se. On the other hand, it has been suggested that HPA axis dysregulation is a potential risk factor for the development of depression. In line with this, several studies reported that L-Dopa treatment may alter the serum levels of ACTH, PRL, and glucocorticoids in parkinsonian patients and Parkinson’s disease animal models. In the present study, we determined whether the chronic treatment with L-Dopa altered the stress response inducing depressive-like behaviours. Adult male Wistar rats were treated orally during 24 days with LEBOCAR® - commercial formulation of L-Dopa (75 mg/day) and Carbidopa (7.5 mg/day) - in drinking water. Animals were stressed by immobilization during the last 9 days of treatment and depressive-like behaviours were assessed by the sucrose intake and forced swimming tests. Behavioural tests showed no signs of depressive-like behaviours in the LEBOCAR®-treated and/or stressed rats. We next explored the SAM axis reactivity. Circulating noradrenaline and adrenaline increased in rats treated with LEBOCAR® (p<0.05; HPLC). Also, the adrenals from stressed animals showed higher content of adrenaline (p<0.05). Then, we studied the HPA axis activity. Chronically stressed rats displayed a lower ACTH secretion (ELISA) and a downregulation of POMC expression (qPCR) in the anterior pituitary (p<0.05). In addition, LEBOCAR® treatment induced a reduction in serum ACTH and POMC levels (p<0.05). As expected, serum corticosterone (ELISA) enhanced under chronic stress, an effect that was inhibited by treatment with LEBOCAR® (p<0.05). Finally, pituitary PRL gene expression (qPCR) was downregulated by LEBOCAR® treatment with a more pronounced effect when rats were also stressed (p<0.05). Our results suggest that L-Dopa alters the neuroendocrine stress response enhancing SAM axis reactivity and reducing HPA axis activity and PRL expression.

Mental fatigue accompanied with whole body cold exposure before exercise impairs endurance exercise performance

Purpose Endurance exercise performance is impaired by cold exposure before exercise via an enhanced sympathetic activation. Mental fatigue induced by psychological task before exercise deteriorates endurance exercise performance, but the impact of a simultaneous load of mental fatigue and cold exposure on endurance exercise performance is remained unknown. The purpose of this study is to test the hypothesis that mental fatigue during cold exposure before exercise further impairs endurance exercise performance. Methods Nine male young subjects performed the Stroop color word test (500 stimuli/set×2, 55 min in total) as mental stress (MS) trial, while watched a documentary DVD as control (CON) trial during whole body cold exposure using a water-perfused suit (10˚C for 10 min then 15˚C for 50 min). After that participants performed a cycling test at 80% VO2max to the exhaustion after warm-up for 4 min. Subjective fatigue index (SFI) were measured before and immediately after mental stress and exercise. Plasma adrenaline ([Ad]p), noradrenaline ([Norad]p), and cortisol ([Corti]p) concentrations were measured before and immediately after mental load and exercise. Time to exhaustion (TE) was evaluated as endurance cycling performance. This study received an ethics approval from our institution. Results Percent changes from baseline of SFI were higher in the MS trial than in the CON trial at post Intervention and post exercise (p < 0.001). Significant effects of interaction (time × trial) were found on [Ad]p (p = 0.026), while not on [Norad]p nor on [Corti]p. TE was shortened but not significantly for the MS trial (767 ± 63 s) compared with the CON trial (813 ± 51 s), and an effect size of the difference was d = 0.271. The difference (Δ) between the trials (MS - CON) of TE was negatively correlated with Δ[Ad]p (r = - 0.605, p = 0.085) or Δ[Norad]p (r = - 0.661, p = 0.074), but not with Δ[Corti]p (r=0.251, p=0.514) determined immediately after exercise. Conclusions These findings support our hypothesis, thus mental fatigue accompanied with whole body cold exposure before exercise would further impair endurance exercise performance compared with cold exposure alone via the enhanced sympathoadrenal medullary system rather than hypothalamic pituitary adrenal system.