Epinephrine Concentrations Research Articles

Mo1673 HYDRAULIC INFUSION OF EPINEPHRINE-CONTAINING SALINE IS EFFECTIVE IN PREVENTING POSTOPERATIVE BLEEDING DURING ANTICOAGULANTS COLD SNARE POLYPECTOMY

Cold snare polypectomy has recently been reported to be useful in the treatment of colorectal polyps and has become widely used worldwide. For HSP using a radiofrequency generator, CSP is recognized to have a lower risk of post-polyp bleeding and fewer bleeding complications, one of the post-polyp syndrome, because it does not perform heat coagulation, although bleeding occurs immediately after polyp removal. However, recent advances in anticoagulants have led to the administration of antithrombotic agents such as NOAC and aspirin in a large number of cases for the purpose of preventing cardiovascular diseases, and antithrombotic agents have been increasingly administered in colorectal polypectomy. Therefore, it is necessary to pay attention to the prevention of bleeding after CSP. Generally, the injection of physiological saline using the water jet mechanism is used to prevent bleeding after CSP, and we examined whether the addition of a small amount of epinephrine to the saline can prevent postoperative bleeding. From January 2018 to March 2019, 200 patients who underwent CSP with an antithrombotic agent in our hospital were randomly assigned to receive either saline infusion after CSP (NS group) or epinephrine infusion (ES group) and prospectively enrolled to determine the presence of postoperative bleeding events. As the concentration of epinephrine, 0.1%-2 ml/1A dissolved in 200 ml physiological saline was used as a 100-fold dilution. NS group was injected with saline after CSP, and ES group was injected with epinephrine added saline after CSP. All procedures for CSP and equipment such as snares were the same. Post-CSP fluid infusion was terminated in both groups when the ablated surface bulged, and hemostasis was achieved using Olympus OFP -2 as a Water Jet device. Postoperative bleeding events were defined as the occurrence of anal bleeding from the day following polypectomy. In the CSP, all cases were examined, and only those diagnosed as adenoma by the diagnosis of JNET TYPE 2A by the magnifying observation of NBI or BLI were examined. Postoperative bleeding occurred in 2/100 of patients in the NS group. In the ES group, 0/100 patients had postoperative bleeding. There were no differences in polyp size, location, or histology between the two groups. There was no difference in antithrombotic therapy between the two counties. Hydraulic infusion of epinephrine in anticoagulated cold snare polypectomy is effective in preventing postoperative bleeding.

Unreliability of EDTA samples for measuring bioamine neurotransmitter levels in cats.

The aim of this study was to assess the reliability of an EDTA-based method for measuring cat blood bioamines. Test 1 involved collecting blood samples from seven university laboratory cats. The samples were transferred to EDTA, heparin and plain tubes to determine concentrations of four bioamines (serotonin, dopamine, epinephrine [adrenaline] and norepinephrine [noradrenaline]). Correlation of measurements performed on EDTA plasma, with those performed on heparinized plasma or serum were assessed by intraclass correlation coefficients (ICCs). In test 2, blood samples from five owned cats were collected and stored in EDTA tubes and divided between duplicate Eppendorf tubes labeled as different cats for blinding purposes and analyzed independently for the same four bioamines as in test 1. Reliability of concentration determination for these duplicates was assessed by ICCs and coefficients of variation (CVs). In test 1, there was no significant correlation between the EDTA plasma serotonin and serum serotonin concentrations. There was also no significant correlation between EDTA plasma and heparin plasma concentrations for either epinephrine or norepinephrine. There was a statistically significant but weak correlation between EDTA plasma and heparin plasma dopamine concentrations. In test 2, there was no correlation for repeat-analyzed serotonin and epinephrine concentrations. Although there were statistically significant correlations for dopamine and norepinephrine, CVs for each analyte were in excess of 30%. Before any further attempt is made to measure and report on neurotransmitter concentrations in domestic cats, it is essential that the robustness of the methodology is carefully validated and the data presented.

Synthesis of enhanced fluorescent graphene quantum dots for catecholamine neurotransmitter sensing

We employed polypyrrole/graphene quantum dot (PPy/GQD) composites as a sensor for the simple and selective detection of catecholamine neurotransmitters (CNs), such as dopamine (DA), epinephrine (EP), norepinephrine (NE), which play vital roles in the peripheral and central nervous systems. The PPy/GQD composites showed strong fluorescence emission, which was significantly increased, by as much as greater than three times, compared to that of the pristine GQDs. In neutral solution, the CNs on the surface of the PPy/GQD composites were converted into a quinone structure, which triggered the fluorescence quenching of the PPy/GQD composites via a photo-induced electron transfer process. The CN concentration could be effectively monitored based on the quenching of the fluorescence signal of the PPy/GQDs. The quenching effect of DA is the fastest and most effective, followed by those of EP and NE, respectively, and the quenched fluorescence intensity of the PPy/GQDs was proportional to the concentration of DA (0.007–250 μM), EP (0.7–250 μM), and NE (5–500 μM). The present system was used for the quantification of CNs in human serum samples with acceptable results.

Tibial Intraosseous Administration of Epinephrine Is Effective in Restoring Return of Spontaneous Circulation in a Pediatric Normovolemic But Not Hypovolemic Cardiac Arrest Model.

We compared the efficacy of tibial intraosseous (TIO) administration of epinephrine in a pediatric normovolemic versus hypovolemic cardiac arrest model to determine the incidence of return of spontaneous circulation (ROSC) and plasma epinephrine concentrations over time. This experimental study evaluated the pharmacokinetics of epinephrine and/or incidence of ROSC after TIO administration in either a normovolemic or hypovolemic pediatric swine model. All subjects in the TIO normovolemia cardiac arrest group experienced ROSC after TIO administration of epinephrine. In contrast, subjects experiencing hypovolemia and cardiac arrest were significantly less likely to experience ROSC when epinephrine was administered TIO versus intravenous (TIO hypovolemia: 14% [1/7] vs IV hypovolemia: 71% [5/7]; P = 0.031). The TIO hypovolemia group exhibited significantly lower plasma epinephrine concentrations versus IV hypovolemia at 60, 90, 120, and 150 seconds (P < 0.05). Although the maximum concentration of plasma epinephrine was similar, the TIO hypovolemia group exhibited significantly slower time to maximum concentration times versus TIO normovolemia subjects (P = 0.004). Tibial intraosseous administration of epinephrine reliably facilitated ROSC among normovolemic cardiac arrest pediatric patients, which is consistent with published reports. However, TIO administration of epinephrine was ineffective in restoring ROSC among subjects experiencing hypovolemia and cardiac arrest. Tibial intraosseous-administered epinephrine during hypovolemia and cardiac arrest may have resulted in a potential sequestration of epinephrine in the tibia. Central or peripheral intravascular access attempts should not be abandoned after successful TIO placement in the resuscitation of patients experiencing concurrent hypovolemia and cardiac arrest.

The study on the effect of depression on breast cancer incidence through IDO/kynurenine pathway.

e13569 Background: Psychosocial factors have been considered as the most common causes for women with breast cancer. However, it remains unclear whether mental stress can influence cancer incidence and progression. This study aims to investigate the relationship between them and the potential molecular mechanism. Methods: Depression model was established by restricting MMTV-PyMT mice in a 50ml-fixator for 4 h per day for 21 consecutive days. Behavioral tests including light-dark box test, open-field test and force swimming test were performed. Then blood, brain and mammary samples were collected at the indicated time points. ELISA was used to detect the concentration of neurotransmitters serotonin, epinephrine and norepinephrine and inflammatory factors IL-6, TNF-a and IL-1β in brain tissue and serum. Real-time quantitative qPCR and western blot were used to detect indoleamine 2, 3-dioxygenase (IDO) expression. The level of tryptophan was measured by high performance liquid chromatography(HPLC). Flow cytometry was used to evaluate the exhaustion of CD8+ T cells. Besides, the correlation between IDO expression detected by immunohistochemistry and the severity of mammary tumors was analyzed in the tumor specimens. Results: We observed that chronic stress caused depression-like behaviors, abnormal secretion of neurotransmitters serotonin, epinephrine and norepinephrine and promoted the development of breast cancer in MMTV-PyMT mice. Depression elevated the secretion of inflammatory factors IL-6, TNF-a and IL-1β in brain tissue and serum, which upregulated the expression of IDO and decreased the level of tryptophan in mice. Furthermore, T cells are sensitive to low tryptophan concentration, so elevated IDO expression suppressed and exhausted CD8+ T cells, ultimately promoting cancer incidence. Administration of xiaoyao pill (a well-known Chinese herbal formula for treating depression) or IDO inhibitor reversed the depression-like behaviors in mice and slowed the development of breast cancer. At the same time, the analysis of clinical samples showed that depression identified by Hamilton Depression Scale(HAMD) and IDO expression in mammary tumor tissues were positively correlated with the severity of mammary tumors. Conclusions: Altogether, our results suggest that depression can promote tumor immune privilege and cancer occurrence through inducing upregulated IDO expression.

Experiences of Discrimination and Urinary Catecholamine Concentrations: Longitudinal Associations in a College Student Sample.

Experiences of discrimination are a risk factor for subsequent cardiovascular disease. However, there is a lack of longitudinal research examining associations between discrimination and urinary catecholamines. This is surprising given the likely mediating role of sympathetic nervous system dysregulation in the association between psychosocial stress and cardiovascular morbidity. The current study examined the 3 year longitudinal association between experiences of discrimination and urinary catecholamines. The sample included 149 college students (mean age at baseline = 18.8, standard deviation = 0.96; 45% Black/African American; 55% White/European American). Concentrations of epinephrine and norepinephrine-urinary catecholamines with established links to psychosocial stress exposure and subsequent morbidity-were determined from 12 hr overnight samples. Results indicated that experiences of discrimination were associated with increases in both epinephrine (β = .284, standard error [SE] = .117, p = .015) and norepinephrine (β = .306, SE = .114, p = .001). These longitudinal associations persisted after adjusting for negative affect, depression, and rejection sensitivity and did not vary as a function of race/ethnicity. Results suggest that examination of overnight urinary catecholamines as a biological mediator of associations between experiences of discrimination and cardiovascular morbidity is warranted.

MON-LB110 A Phase 2 Evaluation of a Ready-To-Use Liquid Stable Continuous Subcutaneous Glucagon Infusion for the Treatment of Hypoglycemia Associated Autonomic Failure

OBJECTIVE:A novel, ready-to-use, liquid stable, continuous subcutaneous glucagon infusion (CSGI; Xeris Pharmaceuticals) was evaluated for the treatment of adults with type 1 diabetes (T1D) with documented Hypoglycemia Associated Autonomic Failure (HAAF). METHOD:This was a Phase 2 prospective, multi-center, randomized, placebo-controlled, double-blind, parallel trial in T1D adults with documented HAAF, defined as Gold Scale Score ≥4. Subjects were randomized in a 1:1:1 ratio to receive 4 weeks of continuous treatment (via Omnipod pump) with high rate CSGI (80mcg/hour), low rate CSGI, (20mcg/hour) or placebo (matched infusion rates for low and high rate CSGI). The primary endpoint evaluated at 4 weeks was the percent change of the epinephrine hormone response after 30 minutes of induced hypoglycemia. Epinephrine levels and hypoglycemia symptoms were recorded following a stepwise hypoglycemia clamp, and results compared between study treatment arms. Following the first four weeks, subjects continued for an additional 24 weeks to assess their epinephrine hormone response to hypoglycemia measured at 3 months post-treatment (16 weeks), and 6 months post-treatment (28 weeks). RESULTS:Forty-nine subjects were randomized to receive treatment with high rate CSGI (n=15), low rate CSGI (n=18), or matching placebo (n=16). At the end of study treatment, there were no statistically significant differences between the treatment arms for percent change of epinephrine hormone response during a stepwise hypoglycemia clamp (CSGI vs. placebo; p=0.160). As a result, long-term follow-up of the subjects was stopped early. The long-term follow-up data collected to date will be reported separately. The administration of low and high rate CSGI was associated with mild to moderate nausea (5.9%, 20%, respectively) and vomiting (11.8%, 13.3%, respectively) that was self-limited and required no additional intervention. In this 4-week assessment, CSGI was not associated with pain nor significant injection site reactions, and no SAEs related to CSGI were reported. CONCLUSION:In this proof-of-concept study, CSGI did not demonstrate statistically significant improvements in plasma epinephrine concentration when compared to placebo at 4 weeks. While there were positive epinephrine and improved hypoglycemia awareness responses observed in some subjects, the equivocal efficacy results observed may be explained by the unanticipated and incomplete elimination of hypoglycemia on CSGI therapy, and those on placebo therapy experienced hypoglycemia improvement. CSGI can be safely used with concomitant diabetes medications, and there were no SAEs related to CSGI. The 4-week administration of both low and high rate CSGI was safe and well tolerated.

Exposure to total 36-hr sleep deprivation reduces physiological and psychological thermal strain to whole-body uncompensable passive heat stress in young adult men.

Total sleep deprivation (TSD) is associated with endothelial dysfunction and a consequent decrease in vascular reactivity and increase in peripheral vascular resistance. These effectors compromise the body's ability to thermoregulate in hot and cold stress conditions. We investigated heat-unacclimated young adult men (26±2years) to determine whether 36hr of TSD compared to an 8 or 4-hr sleep condition, would suppress the responses of the autonomic system (body rectal temperature [Tre ], heart rate [HR], root mean square of successive interbeat intervals, physiological strain, blood pressure [BP], circulating blood catecholamines, sweating rate and subjective sensations) to whole-body uncompensable passive heat stress in traditional Finnish sauna heat (Tair =80-90°C, rh=30%). Sauna bathing that induced whole-body hyperthermia had a residual effect on reducing BP in the 8-hr and 4-hr sleep per night conditions according to BP measurements. By contrast, 36hr of total wakefulness led to an increase in BP. These observed sleep deprivation-dependent differences in BP modifications were not accompanied by changes in the blood plasma epinephrine and norepinephrine concentrations. However, during sauna bathing, an increase in BP following 36hr of TSD was accompanied by significant decreases in body Tre , HR and physiological strain, together with a diminished sweating rate, enhanced vagus-mediated autonomic control of HR variability, and improved thermal perception by the subjects. Our results suggest the impaired ability of the body to accumulate external heat in the body's core under uncompensable passive heat conditions following 36hr of TSD, because of the TSD-attenuated autonomic system response to acute heat stress.

Usage of Epinephrine Mixed With Lidocaine in Plastic Surgery.

Plastic surgeons commonly administer subcutaneous epinephrine to reduce intraoperative blood loss. The authors hypothesized that there are safe and effective concentration of epinephrine for vasoconstriction and their durations. The aim of this study is to summarize the existing literatures for the usage of epinephrine mixed with lidocaine in plastic surgical field.In 1903, Braun reported that adrenaline prolonged the local anesthetic effects of cocaine. The Parke-Davis Company began selling cocaine with adrenaline, as well as combining adrenaline with new synthetic local anesthetics.Based on a review of the literature, concentrations between 1:50,000 and 1:400,000 are equally effective and provide superior vasoconstriction compared with more dilute solutions. If epinephrine is further diluted, its onset and time to peak serum concentration are delayed, and its duration of action is shortened. When lidocaine is used without epinephrine, duration of anesthesia is shortened reverse proportionally to the lidocaine concentration. When lidocaine is used with epinephrine, duration of anesthesia is prolonged proportionally to the lidocaine concentration. With slow injection rate in the soft tissue, the maximum safe dose of lidocaine is approximately 3 mg/kg plain and 7 mg/kg when mixed with epinephrine. Lidocaine may protect the myocardium because of its antiarrhythmic activity, which is the rationale for infiltrating lidocaine mixed with epinephrine in general anesthesia.In plastic surgery, subcutaneous infiltration of epinephrine-lidocaine solution is performed to reduce intraoperative blood loss. Even in general anesthesia, infiltrating lidocaine mixed with epinephrine may protect the myocardium because of its antiarrhythmic activity.

Influence of Preemptive Analgesia with Oxycodone Hydrochloride on Stress Hormone Level of Geriatric Patients undergoing Gastrointestinal Surgery.

To determine the influence of preemptive analgesia with oxycodone hydrochloride on stress hormone level of geriatric patients undergoing gastrointestinal surgery, and evaluate the analgesic effect. Rrandomised controlled trial. Department of Anaesthesiology, Baoding First Central Hospital, from January to December 2017. Geriatric patients who were to undergo gastrointestinal surgery were classified into observation group and control group of 30 patients each. For the observation group, intravenous injection of 0.1mg/kg oxycodone hydrochloride injection was conducted 10 mins before anesthesia induction. For the control group, intravenous injection of 10 ml normal saline was conducted. Eight ml of venous blood was drawn 10 mins before injection (T0), after operation (T1), 2 hours after operation (T2), 6 hours after operation (T3), and 24 hours after operation (T4). Serum concentration of cortisol, epinephrine, noradrenaline was determined after the completion of surgery (T1), 2-hour after surgery (T2), 6-hour after surgery (t3) and 24-hour after sutrgery (T4). for both groups. Visual analogue scale (VAS) score was used for assessment of pain when the surgery was completed; and after the surgery, was compared for both groups. Serum concentrations of epinephrine and noradrenaline in observation group were significantly reduced at T1 and T2 (p <0.05), and serum concentrations of cortisol and glucose were significantly reduced at T1, T2 and T3 (p <0.05). At 2 and 6-hours after operation, the VAS score was significantly lower than that of the control group (p<0.05). Giving oxycodone hydrochloride to geriatric patients receiving gastrointestinal surgery can reduce stress hormone release in the postoperative period, and can facilitate postoperative recovery. Key Words: Sold, Gastrointestinal surgery, Oxycodone hydrochloride, Preemptive analgesia, Stress response.

Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis

IntroductionThe habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has...

Outcomes and Complications with Topical Epinephrine in Endoscopic Sinus Surgery: A Systematic Review and Meta‐analysis

To assess the safety and efficacy of topical epinephrine in adults undergoing endoscopic sinus surgery (ESS). PubMed, Embase, and Ovid MEDLINE online databases. Non-case report English articles studying the effects of topical epinephrine as the topical vasoconstrictor used in adult ESS were found from the online databases through January 2019. The PRISMA literature selection process was used (Preferred Reporting Items for Systematic Reviews and Meta-analyses). An overall 2216 articles were identified, with 9 meeting inclusion criteria involving a total of 5043 patients. All 9 studies assessed the safety of topical epinephrine, while 5 examined efficacy. Intraoperative average blood loss (ABL) ranged from 60 to 426 mL. Topical epinephrine concentrations varied from 1:1000 to 1:100,000, and 3 major complications were found for a rate of 0.06%. There were no reports of ophthalmic, orbital, or skull base injury, nor were there reports of cerebrospinal fluid leaks. A meta-analysis was performed on the 4 studies examining ABL. Estimated mean (95% CI) ABL was 119.4 mL (39.1-199.6) in the higher-concentration cohort (>1:10,000) and 372.2 mL (296.8-447.5) in the lower-concentration cohort (≤1:10,000) (P = .001). Topical epinephrine is generally safe and provides acceptable hemostasis during ESS, with higher concentrations (>1:10,000) providing improved hemostasis. Caution is advised for its use in patients with preexisting cardiovascular disease or in combination with other topical or injected vasoconstrictive agents. More prospective comparative studies are necessary to determine the ideal hemostatic concentration of epinephrine in ESS.

Intranasal epinephrine effects on epinephrine pharmacokinetics and heart rate in a nasal congestion canine model

BackgroundHistamine release and vasodilation during an allergic reaction can alter the pharmacokinetics of drugs administered via the intranasal (IN) route. The current study evaluated the effects of histamine-induced nasal congestion on epinephrine pharmacokinetics and heart rate changes after IN epinephrine.MethodsDogs received 5% histamine or saline IN followed by 4 mg epinephrine IN. Nasal restriction pressure, epinephrine concentration, and heart rate were assessed. Maximum concentration (Cmax), area under plasma concentration-time curve from 1 to 90 min (AUC1–90), and time to reach Cmax (Tmax) were measured. Clinical observations were documented.ResultsIn the 12 dogs in this study, nasal congestion occurred at 5–10 min after IN histamine administration versus no nasal congestion after IN saline. After administration of IN epinephrine, IN histamine-mediated nasal congestion was significantly reduced to baseline levels at 60, 80, and 100 min. There were no significant differences in Cmax and AUC1–90 between histamine and saline groups after IN epinephrine delivery (3.5 vs 1.7 ng/mL, p = 0.06, and 117 vs 59 ng/mL*minutes, p = 0.09, respectively). After receiving IN epinephrine, the histamine group had a significantly lower Tmax versus the saline group (6 vs 70 min, respectively; p = 0.02). Following IN epinephrine administration, the histamine group showed rapidly increased heart rate at 5 min, while there was a delayed increase in heart rate (occurring 30–60 min after administration) in the saline group. Clinical observations included salivation and emesis.ConclusionIN histamine led to more rapid epinephrine absorption and immediately increased heart rate compared with IN saline. IN epinephrine decreased histamine-induced nasal congestion.

Synthesis and Characterization of Iron Phthalocyanine Supported on Graphene Oxide and Catalysis of Adrenaline

Iron tetranitro-phthalocyanine was synthesized by the reaction of 4-nitrophthalimide with FeCl₃, and was then modified by γ-(trimethoxysilyl)propane-1-thiol to prepare functionalized iron phthalocyanine. A graphene oxide/iron phthalocyanine composite was then prepared, comprising functionalized iron phthalocyanine supported on the surface of graphene oxide via covalent bonds. All these complexes were characterized by infrared spectra (IR), X-ray diffraction, ultraviolet/visible (UV/vis) and Raman spectroscopy, and scanning electron microscopy. The catalytic properties of the graphene oxide/iron phthalocyanine composite for catalyzing adrenaline oxidation were evaluated by measuring the absorbance intensity at the characteristic peak of the oxidation product. A fiberoptic adrenaline sensor based on a graphene oxide/iron phthalocyanine composite catalyst and fluorescence quenching was fabricated and studied. The relationship between the concentrations of dissolved oxygen and adrenaline was investigated by measuring the phase delay φ. The results showed that the graphene oxide/iron phthalocyanine composite can effectively catalyze adrenaline oxidization, and the optimal conditions are pH = 8.0, T = 30 °C, and mGO-FePc = 4.0 mg/mL; moreover, concentrations of adrenaline can be detected in the range from 1.8×10-6 to 9.2×10-5 mol/L with a sensor response time of 4 min.

Sensitive Determination of Epinephrine in the Presence of Ascorbic Acid at Poly(diphenylamine sulfonic acid) Modified Sensor

A sensitive and simple modified sensor was prepared by electrodeposition of diphenylamine sulfonic acid (DPSA) to the glassy carbon electrode surface by cyclic voltammetry (CV) technique. The electrooxidation of epinephrine (EP) was accomplished by CV and differential pulse voltammetry at poly(DPSA) modified sensor. As a result of the findings, the current values were enhanced and both substances were separated at the modified sensor compared to the bare electrode. There was linearly between the oxidation current and concentration of EP from 0.2 to 100 μM in phosphate buffer solution at pH 7.0. The limit of detection was 5.0 nM and the sensitivity was 0.4205 μA/μM. The determination of EP was successfully and satisfactorily carried out in real samples such as human blood serum and urine at the poly(DPSA) sensor. To the best knowledge of this work, this is the first study that detect the EP in the presence of ascorbic acid at poly(DPSA) sensor in the literature.

Effect of Cold Exposure and Exercise on Carbohydrate and Lipid Metabolism in Persons with Cervical Spinal Cord Injury

ObjectiveRates of retiring for Oita International Wheelchair Marathon in the last decade were higher with the lower atmospheric temperature below 22°C. The tendency was stronger in persons with cervical spinal cord injury (CSCI) than the other classes (unpublished data), which may be associated with deteriorated lipid utilization and a faster depletion of glycogen in a whole body. Our purpose was to examine whether serum profile of lipid in CSCI during cold stress and exercise was different from able‐body persons (AB) or varied dependent on the injury level.Methods[Protocol1] Nine CSCI and 11 AB wore a water‐perfused suit and took a supine position then 33‐°C water was perfused into the suit. After 10‐min measurement of thermoneutral condition, 25‐°C water was perfused for 20min (CS), then perfused 33‐°C water for 60min, while monitoring esophageal (Tes) and mean skin temperatures (Tsk). Blood samples were taken before, just after, 60‐ and 120min after CS. [Protocol2] Six of each CSCI and AB did a 30‐min arm crank exercise at 50% VO2peak then took a sitting position for 60min as a recovery. Blood samples were taken before, just after and an hour after exercise. [Protocol3] Bloods were sampled from 5 CSCI and 9 thoracic and lumbar SCI (LSCI), who completed a half marathon, before, just after and an hour after the race. Plasma concentrations of adrenaline ([Ad]p), noradrenaline ([Nor]p), and glucose ([Glc]p), and serum concentrations of insulin ([Ins]s), free fatty acid ([FFA]s), and total ketone bodies ([tKB]s) were assessed in all protocols.Results[Protocol1] Tsk decreased by ~2 °C during CS and Tes decreased by ~0.2 °C after CS with no significant differences between groups. VO2 was similar between groups and remained unchanged throughout the study. Respiratory quotient was significantly decreased in AB after CS but remained unchanged in CSCI. [Ad]p and [Nor]p were lower in CSCI than AB and [Nor]p significantly increased only in AB during recovery. [Glc]p before, immediately and one hour after CS was higher in CSCI but it decreased to the same level as AB 2 hours later. [FFA]s did not differ between groups and decreased after CS in only AB. [tKB]s significantly increased after CS in both groups, but the increase started from 1‐hour recovery in CSCI. [Protocol2] [Ad]p and [Nor]p increased just after exercise in AB but not in CSCI. [Glc]p remained unchanged in both groups but [Ins]s started to decrease just after exercise in CSCI, earlier than AB. [tKB]s increased from the baseline an hour after exercise in CSCI but not in AB, while [FFA]s did not differ between groups. [Protocol3] [Ad]p and [Nor]p was lower in CSCI than LSCI and increased just after the race only in LSCI and returned to the baseline at an hour after the race. [FFA]s increased just after the race in CSCI and remained the higher level at an hour after race, then [tKB]s increased an hour after the race only in CSCI. Both lipid profiles remained unchanged throughout the study in LSCI.ConclusionIt is suggested that lipolysis and ketogenesis are likely to enhance in CSCI during cold or exercise. Lipid and glucose metabolisms vary dependent on the injury level with SCI.Support or Funding InformationThis work was funded by Nachikatsuura Research foundation and Kyoten, Wakayama Med. Univ.

Intranasal epinephrine in dogs: Pharmacokinetic and heart rate effects.

Epinephrine is the standard of care for the treatment of severe allergy and anaphylaxis. Epinephrine is most often administered through the intramuscular (IM) route via autoinjector. The current study aimed to evaluate an alternative method of epinephrine treatment through intranasal (IN) delivery in dogs. The pharmacokinetic (PK) parameters of maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration‐time curve from 0 to 90 minutes (AUC0–90) were observed after IN epinephrine (2, 3, 4, 5, 10, and 20 mg) and IM epinephrine via autoinjector (0.15 and 0.3 mg) for 90 minutes. Heart rate effects were measured after IN (2 and 5 mg) and IM (0.15 and 0.3 mg) epinephrine administration. IN epinephrine (5 mg) demonstrated significantly greater plasma epinephrine concentration at 1 minute as compared with IM epinephrine (0.3 mg) (1.68 ± 0.65 ng/mL vs 0.21 ± 0.08 ng/mL, P = .03). There were no significant differences in Cmax, Tmax, and AUC0–90 between 2‐mg IN and 0.15‐mg IM epinephrine or between 5‐mg IN and 0.3‐mg IM epinephrine. IN epinephrine reduced heart rate increases, as compared to IM epinephrine. IN and IM epinephrine were both well‐tolerated. Overall, IN epinephrine demonstrated advantages over IM epinephrine, including the rapid increase in plasma epinephrine and lack of increased heart rate over time.

Morphological and Cytophysiological Changes in the Adult Rat Adrenal Medulla after Prenatal and Postnatal Exposure to Endocrine-Disrupting DDT.

The aim of the investigation was to study morphological and cytophysiological changes in the adult rat adrenal medulla after prenatal and postnatal exposure to endocrine-disrupting chemical dichlorodiphenyltrichloroethane (DDT).Materials and MethodsThe experiment was carried out on male Wistar rats (n=30). The rats were exposed to low doses of DDT during prenatal and postnatal development (n=10) and during postnatal development (n=10) only. The average daily intake of DDT by rats was 3.30±0.14 μg/kg. The control (n=10) and experimental animals were sacrificed at the age of 10 weeks (post-puberty), when rat adrenal glands reached their maximum development. Histological samples of the equatorial sections of the adrenal glands were prepared. The adrenal medulla was studied using light microscopy and computer morphometry. Immunohistochemistry was performed to evaluate tyrosine hydroxylase expression in chromaffin cells. Plasma epinephrine content was measured using enzyme-linked immunosorbent assay.ResultsPostnatal exposure of rats to low doses of the endocrine disruptor was found to interfere with adrenal medulla development and cytophysiology of chromaffin cells. Prenatal and postnatal exposure resulted in more profound delay in adrenal medulla development of adult rats as compared to the values of rats exposed postnatally, which was manifested by reduced area of the adrenal medulla and reduced total area of chromaffin cells in its section. Postnatal exposure is manifested by more significant functional disorders including decreased synthesis of tyrosine hydroxylase enzyme in the cytoplasm of chromaffin cells and elevated number of tyrosine-hydroxylase-negative cells in the medulla section, leading to a decrease in plasma epinephrine concentration.ConclusionExposure to low doses of DDT in the early stages of development leads to morphological and cytophysiological changes in the adult rat adrenal medulla and, therefore, reduced functional activity of chromaffin cells, which allows considering the endocrine disruptor DDT a potential risk factor disrupting the function of the neuroendocrine system.

Effect of Sacubitril/Valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes?

We assessed the effect of Sacubitril/Valsartan on circulating catecholamine levels in patients with HF in an observational cohort study. We included 108 consecutive HF patients attending our HF Outpatients Clinic who were eligible to Sacubitril/Valsartan according to the PARADIGM-HF inclusion and exclusion criteria. We furthermore included 58 stable HF patients under optimal medical therapy as a control group. Norepinephrine and epinephrine were measured with immunoradiometric assays at baseline, at 3- and at 6-month time follow-up. Compared to baseline levels there was no change at three months in epinephrine (p = 0.177) or norepinephrine (p = 0.815) concentrations. At 6 months norepinephrine remained unchanged (p = 0.359). However, at 6 months we observed a significant increase in epinephrine levels compared to baseline [66 pg/mL (37−93) vs 38 pg/mL (18–74), p < 0.001]. In the control group no change was observed in epinephrine levels compared to baseline (p = 0.838). This study is the first to report on the effect of the new drug Sacubitril/Valsartan on circulating catecholamine levels in HF patients. Our data show a significant increase in epinephrine levels during a 6 month follow up in stable HF patients.

Arrhythmogenic Interaction Between Sympathetic Tone and Mechanical Stretch in Rat Pulmonary Vein Myocardium.

Rapid firing from pulmonary veins (PVs) frequently initiates atrial fibrillation, which is a common comorbidity associated with hypertension, heart failure, and valvular disease, i.e., conditions that pathologically increase cardiomyocyte stretch. Autonomic tone plays a crucial role in PV arrhythmogenesis, while its interplay with myocardium stretch remains uncertain. Two-microelectrode technique was used to characterize electrophysiological response of Wistar rat PV to adrenaline at baseline and under mild (150 mg of applied weight that corresponds to a pulmonary venous pressure of 1 mmHg) and moderate (10 g, ∼26 mmHg) stretch. Low concentrations of adrenaline (25–100 nmol/L) depolarized the resting membrane potential selectively within distal PV (by 26 ± 2 mV at baseline, by 18 ± 1 mV at 150 mg, P < 0.001, and by 5.9 ± 1.1 mV at 10 g, P < 0.01) suppressing action potential amplitude and resulting in intra-PV conduction dissociation and rare episodes of spontaneous activity (arrhythmia index of 0.4 ± 0.2, NS vs. no activity at baseline). In contrast, 1–10 μmol/L of adrenaline recovered intra-PV propagation. While mild stretch did not affect PV electrophysiology at baseline, moderate stretch depolarized the resting potential within distal PV (-56 ± 2 mV vs. -82 ± 1 mV at baseline, P < 0.01), facilitated the triggering of rapid PV firing by adrenaline (arrhythmia index: 4.4 ± 0.2 vs. 1.3 ± 0.4 in unstretched, P < 0.001, and 1.7 ± 0.8 in mildly stretched preparations, P < 0.005, at 10 μmol/L adrenaline) and induced frequent episodes of potentially arrhythmogenic atrial “echo” extra beats. Our findings demonstrate complex interactions between the sympathetic tone and mechanical stretch in the development of arrhythmogenic activity within PVs that may impact an increased atrial fibrillation vulnerability in patients with elevated blood pressure.