Showing papers on "Epinephrine published in 2015"
TL;DR: Analysis of the data supports the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinesphrine in anaphylaxis, and suggests the risk of overdose and adverse CV events is significantly higher withIV bolusEpinephrine administration.
155 citations
TL;DR: Among children with in-hospital cardiac arrest with an initial nonshockable rhythm who received epinephrine, delay in administration of epine dopamine was associated with decreased chance of survival to hospital discharge, ROSC, 24-hour survival, and survival toospital discharge with a favorable neurological outcome.
Abstract: Importance Delay in administration of the first epinephrine dose is associated with decreased survival among adults after in-hospital, nonshockable cardiac arrest. Whether this association is true in the pediatric in-hospital cardiac arrest population remains unknown. Objective To determine whether time to first epinephrine dose is associated with outcomes in pediatric in-hospital cardiac arrest. Design, Setting. and Participants We performed an analysis of data from the Get With the Guidelines–Resuscitation registry. We included US pediatric patients (age Exposure Time to epinephrine, defined as time in minutes from recognition of loss of pulse to the first dose of epinephrine. Main Outcomes and Measures The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC), survival at 24 hours, and neurological outcome. A favorable neurological outcome was defined as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale. Results Among the 1558 patients, 487 (31.3%) survived to hospital discharge. The median time to first epinephrine dose was 1 minute (IQR, 0-4; range, 0-20; mean [SD], 2.6 [3.4] minutes). Longer time to epinephrine administration was associated with lower risk of survival to discharge in multivariable analysis (multivariable-adjusted risk ratio [RR] per minute delay, 0.95 [95% CI, 0.93-0.98]). Longer time to epinephrine administration was also associated with decreased risk of ROSC (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.96-0.99]), decreased risk of survival at 24 hours (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.95-0.99]), and decreased risk of survival with favorable neurological outcome (multivariable-adjusted RR per minute delay, 0.95 [95% CI, 0.91-0.99]). Patients with time to epinephrine administration of longer than 5 minutes (233/1558) compared with those with time to epinephrine of 5 minutes or less (1325/1558) had lower risk of in-hospital survival to discharge (21.0% [49/233] vs 33.1% [438/1325]; multivariable-adjusted RR, 0.75 [95% CI, 0.60-0.93]; P = .01). Conclusions and Relevance Among children with in-hospital cardiac arrest with an initial nonshockable rhythm who received epinephrine, delay in administration of epinephrine was associated with decreased chance of survival to hospital discharge, ROSC, 24-hour survival, and survival to hospital discharge with a favorable neurological outcome.
152 citations
TL;DR: In this population of patients with food-induced anaphylaxis, early treatment of FIA with epinephrine was associated with significantly lower risk of hospitalization, and this study supports the benefit of prompt administration ofEpinephrine for the Treatment of FIA.
124 citations
TL;DR: In CVD patients (especially those with ACS), the decision to administer epinephrine for anaphylaxis can be difficult, and its benefits and potential harms need to be carefully considered.
Abstract: Cardiovascular disease (CVD) increases the risk of severe or fatal anaphylaxis, and some medications for CVD treatment can exacerbate anaphylaxis. The aim of this article is to review the effect of anaphylaxis on the heart, the potential impact of medications for CVD on anaphylaxis and anaphylaxis treatment, and the cardiovascular effects of epinephrine. The therapeutic dilemmas arising from these issues are also discussed and management strategies proposed. PubMed searches were performed for the years 1990-2014 inclusive, using terms such as angiotensin-converting enzyme (ACE) inhibitors, adrenaline, allergic myocardial infarction, anaphylaxis, angiotensin-receptor blockers (ARBs), beta-adrenergic blockers, epinephrine, and Kounis syndrome. Literature analysis indicated that: cardiac mast cells are key constituents of atherosclerotic plaques; mast cell mediators play an important role in acute coronary syndrome (ACS); patients with CVD are at increased risk of developing severe or fatal anaphylaxis; and medications for CVD treatment, including beta-adrenergic blockers and ACE inhibitors, potentially exacerbate anaphylaxis or make it more difficult to treat. Epinephrine increases myocardial contractility, decreases the duration of systole relative to diastole, and enhances coronary blood flow. Its transient adverse effects include pallor, tremor, anxiety, and palpitations. Serious adverse effects (including ventricular arrhythmias and hypertension) are rare, and are significantly more likely after intravenous injection than after intramuscular injection. Epinephrine is life-saving in anaphylaxis; second-line medications (including antihistamines and glucocorticoids) are not. In CVD patients (especially those with ACS), the decision to administer epinephrine for anaphylaxis can be difficult, and its benefits and potential harms need to be carefully considered. Concerns about potential adverse effects need to be weighed against concerns about possible death from untreated anaphylaxis, but there is no absolute contraindication to epinephrine injection in anaphylaxis.
73 citations
TL;DR: This mini review includes studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress to investigate sexual dimorphism during exercise.
Abstract: Sexually dimorphic physiologic responses occur during fasting, hypoglycemia, and exercise. The areas covered in this mini review include studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress. Women have greater reliance on lipid metabolism during fasting, hypoglycemia, and exercise while men exhibit preference of carbohydrate utilization. Plasma glucose concentrations were shown to be lower, while free fatty acids (FFA) and lipolysis higher in women compared to men after fasting. Hypoglycemia resulted in significantly reduced epinephrine, norepinephrine, glucagon, growth hormone, pancreatic polypeptide, and hepatic glucose production responses in females as compared to males. Sexual dimorphism during exercise was demonstrated by higher glycerol and FFA responses in women compared to men and higher carbohydrate oxidation rate in men. Mechanisms that can increase lipolytic rates in women include higher total fat mass, enhanced lipolytic sensitivity to epinephrine, and increased activation of β adrenergic receptors.
68 citations
TL;DR: Investigation of triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children found less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphYLaxis, and associations between triggers and atopic histories, patients with severe anAPHylaxis and cardiovascular involvement were found.
Abstract: Background: Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis. Objective: To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children. Method: Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed. Results: One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H 1 antihistamines (96%), H 2 antihistamines (50%), and β 2 agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95%CI0.014-0.43]; p =0.01and OR 9.36 [95%CI2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement ( p <0.01). Conclusions: The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.
35 citations
TL;DR: To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes.
Abstract: Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.
32 citations
31 citations
TL;DR: For infants at risk of anaphylaxis in the community, there are few options with regard to providing an optimal epinephrine dose for first-aid treatment, and the Canadian Society of Allergy and Immunology (CSACI) recommends, for the child weighing less than 15 kg, given the lack of a suitable alternative, prescribing the 0.15 mg epinesphrine autoinjector.
Abstract: Epinephrine (adrenaline) is the treatment of choice for anaphylaxis. While other medications, including H1-antihistamines, H2-antihistamines, corticosteroids, and inhaled beta-2 agonists are often used to treat anaphylaxis in the emergency setting, none of these medications has been shown to reverse anaphylaxis. Fatal anaphylaxis is related to the delayed use of epinephrine. In community settings, epinephrine is available as an auto-injector in two doses, 0.15 mg and 0.3 mg. The recommended dose for children is 0.01 mg per kilogram. For infants at risk of anaphylaxis in the community, there are few options with regard to providing an optimal epinephrine dose for first-aid treatment. The Canadian Society of Allergy and Immunology (CSACI) therefore recommends, for the child weighing less than 15 kg, given the lack of a suitable alternative, prescribing the 0.15 mg epinephrine autoinjector. Adverse effects of an epinephrine dose of 0.15 mg given intramuscularly in infants or children weighing less than 15 kg are expected to be mild and transient at the plasma epinephrine concentrations achieved; therefore, these effects need to be measured against the consequences of not receiving epinephrine at all, which can include fatality.
27 citations
TL;DR: The anti‐atrial fibrillation effects of GS‐458967 (GS‐967), a selective, potent inhibitor of cardiac late Na+ current (INa), were evaluated in a novel model of AF induction that does not require electrical stimuli.
Abstract: GS-967 Suppresses AFIntroduction
The anti-atrial fibrillation (AF) effects of GS-458967 (GS-967), a selective, potent inhibitor of cardiac late Na+ current (INa), were evaluated in a novel model of AF induction that does not require electrical stimuli.
Methods and Results
In 6 closed-chest anesthetized pigs, AF was induced by intrapericardial acetylcholine (1 mL of 100 mM solution) followed within 1 minute by epinephrine (20 μg/kg, i.v., bolus over 1 min). Effects of GS-967 (0.4 mg/kg, i.v., infused over 30 min) on inducibility and duration of AF were analyzed. Administration of acetylcholine followed by epinephrine elicited spontaneous AF that persisted for 12.03 ± 1.22 minutes (mean ± SEM) in all 6 pigs. Following GS-967, AF did not occur in 5 of 6 pigs when plasma concentration was 383 ± 150 nM. In the single animal in which AF could still be induced, the arrhythmia lasted 6.3 minutes. Partial return of AF inducibility occurred in 2 of 6 animals at 90 minutes, when plasma concentration of GS-967 was 228 ± 35 nM. GS-967 reduced the QT interval (P = 0.004), consistent with cardiac late INa inhibition, but did not affect heart rate, mean arterial pressure, QRS duration, or PR interval. Epinephrine infusion alone, tested in a separate group (N = 6), did not provoke AF.
Conclusion
Selective cardiac late INa inhibition with GS-967 suppresses spontaneous induction of AF in a novel model that does not require provocative electrical stimuli. Because this mode of action has only a mild on effect on contractility, it offers an advantage over contemporary anti-AF agents, which can have negative inotropic actions.
26 citations
TL;DR: Clinicians may consider using the IO route to administer epinephrine during CA when there is no preexisting IV access or when IV access is unobtainable, which may be a survival advantage.
Abstract: Cardiopulmonary Resuscitation (CPR), defibrillation, and epinephrine administration are pillars of advanced cardiac life support (ACLS). Intraosseous (IO) access is an alternative route for epinephrine administration when intravenous (IV) access is unobtainable. Previous studies indicate the pharmacokinetics of epinephrine administration via IO and IV routes differ, but it is not known if the difference influences return of spontaneous circulation (ROSC). The purpose of this prospective, experimental study was to determine the effects of humeral IO (HIO) and IV epinephrine administration during cardiac arrest on pharmacokinetics, ROSC, and odds of survival. Swine (N = 21) were randomized into 3 groups: humeral IO (HIO), peripheral IV (IV) and CPR/defibrillation control. Cardiac arrest was induced under general anesthesia. The swine remained in arrest for 2 min without intervention. Chest compressions were initiated and continued for 2 min. Epinephrine was administered and serial blood samples collected for pharmacokinetic analysis over 4 min. Defibrillation and epinephrine administration proceeded according to ACLS guidelines continuing for 20 min or until ROSC.
Seven HIO swine, 4 IV swine, and no control swine had ROSC. There were no significant differences in ROSC, maximum concentration; except at 30 s, and time-to-concentration-maximum between the HIO and IV groups. Significant differences existed between the experimental groups and the control. The HIO delivers a higher concentration of epinephrine than the IV route at 30 s which may be a survival advantage. Clinicians may consider using the IO route to administer epinephrine during CA when there is no preexisting IV access or when IV access is unobtainable.
TL;DR: The purpose of this review is to assess that epinephrine has a quick onset of activity and rapidly antagonizes multiple mediators that are active in anaphylaxis, not H-1 antihistamines or corticosteroids.
Abstract: Purpose of reviewThe purpose of this manuscript is to review the literature in support of epinephrine (adrenaline) as first line of therapy of anaphylaxis, not H-1 antihistamines or corticosteroids.Recent findingsThe purpose of this review is to assess that epinephrine has a quick onset of activity
TL;DR: In this article, muscle metaboreflex-induced increases in mean arterial pressure (MAP) during submaximal dynamic exercise are mediated principally by increases in cardiac output, and the extent to which if any, the periphe...
Abstract: Muscle metaboreflex-induced increases in mean arterial pressure (MAP) during submaximal dynamic exercise are mediated principally by increases in cardiac output. To what extent, if any, the periphe...
TL;DR: Management includes education about safe conditions for exercise, the importance of ceasing exercise immediately if symptoms develop, appropriate use of epinephrine, and, for patients with food-dependent exercise-induced anaphylaxis, avoidance of the culprit food for at least 4 hours before exercise.
TL;DR: NE and EP may play a role in the pathogenesis of EV71 BE complicated with ANS dysregulation and PE, and both NE and EP enhanced the percentages of infected cells and virus titers in EV71 infection in vitro.
Abstract: Background
Enterovirus 71 (EV71) infections may be associated with neurological complications, including brainstem encephalitis (BE). Severe EV71 BE may be complicated with autonomic nervous system (ANS) dysregulation and/or pulmonary edema (PE). ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.
TL;DR: High-dose insulin, lipid emulsion, and VA-ECMO should be considered for refractory cardiac arrest secondary to β-adrenergic antagonist toxicity such as metoprolol.
Abstract: β-Adrenergic antagonist toxicity causes cardiovascular collapse often refractory to standard therapy. Alternative therapies include high-dose insulin, lipid emulsion, and venoarterial extracorporeal membrane oxygenation (VA-ECMO). A 47-year-old man ingested 10 g of metoprolol tartrate in a suicide attempt. Upon emergency department presentation, he was comatose, bradycardic, and hypotensive. Glucagon (14 mg IV) and vasopressor/inotropic support (epinephrine 0.1 μg/[kg min], dobutamine 10 μg/[kg min]) were administered. Despite these therapies, he developed cardiac arrest for 55 minutes, requiring epinephrine (5 mg IV) and vasopressin (40 U IV) with multiple episodes of return of spontaneous circulation. Additional vasopressor administration (vasopressin 0.04 U/min, norepinephrine 0.5 μg/[kg min]) did not improve his hemodynamics. High-dose insulin (250 U IV) and 20% lipid emulsion (100 mL bolus with 200 mL/30 min infusion) were administered, and VA-ECMO was initiated with hemodynamic improvement. His postarrest neurologic examination demonstrated lack of brainstem reflexes and cortical motor response. He awoke 11.5 hours after time of ingestion. Venoarterial extracorporeal membrane oxygenation was discontinued at hospital day 3, and the patient was discharged on hospital day 10 with excellent neurologic recovery. A serum metoprolol level measured 25,000 ng/mL (therapeutic 20-340 ng/mL). High-dose insulin has been shown to be beneficial in β-adrenergic antagonist cardiotoxicity. Lipid emulsion is thought to act as a lipid extractor, lowering serum and tissue levels. Venoarterial extracorporeal membrane oxygenation was used with the above therapies, restoring organ perfusion and allowing intrinsic drug metabolism and elimination. High-dose insulin, lipid emulsion, and VA-ECMO should be considered for refractory cardiac arrest secondary to β-adrenergic antagonist toxicity such as metoprolol.
TL;DR: Cardioprotective effects of melatonin against epinephrine cardiotoxicity were explored in the model of isolated rat heart to fill in the mosaic of information that can lead to the usage ofmelatonin as a therapeutic tool.
Abstract: Epinephrine, in high doses, exhibits cardiotoxicity that is associated with excessive production of free radicals Melatonin is antioxidant and free radical scavenger with cardioprotective properties In our study, cardioprotective effects of melatonin against epinephrine cardiotoxicity were explored in the model of isolated rat heart In the melatonin group, melatonin (50 μmol/l) was present in the perfusion solution during the whole experiment In the control group, perfusion solution contained no melatonin In both of the groups, after 30 min of initial perfusion, epinephrine was applied during 2 min directly into the heart and led to its strong stimulation Changes in the heart function and arrhythmogenesis were evaluated before application of epinephrine and after the decline of its acute effects No significant differences were observed during the initial perfusion However, in the 15th and 20th minute after epinephrine application, indexes of ventricular contraction and relaxation were significantly higher in the melatonin group Likewise, the values of the left ventricular developed pressure were significantly increased in this group in the 15th minute These differences indicate better preservation of contraction and relaxation in the melatonin-treated group Parameters of arrhythmogenesis—arrhythmia score, incidence and total duration of severe ventricular arrhythmias, were not significantly different between the experimental groups However, their markedly lower average values in the melatonin-treated group suggest the reduction of electrical instability by melatonin In conclusion, the obtained data confirm cardioprotective properties of melatonin and fill in the mosaic of information that can lead to the usage of melatonin as a therapeutic tool
TL;DR: It is suggested that SGLT1 in the VMH plays a significant role in the detection and activation of counterregulatory responses to hypoglycemia, and inhibition of S GLT1 may offer a potential therapeutic target to diminish the risk of hypoglyCEmia in diabetes.
Abstract: The objective of this study was to determine whether the sodium-glucose transporter SGLT1 in the ventromedial hypothalamus (VMH) plays a role in glucose sensing and in regulating the counterregulatory response to hypoglycemia, and if so, whether knockdown of in the VMH can improve counterregulatory responses to hypoglycemia in diabetic rats or rats exposed to recurrent bouts of hypoglycemia (RH). Normal Sprague-Dawley rats as well as RH or streptozotocin (STZ)-diabetic rats received bilateral VMH microinjections of an adenoassociated viral vector containing either the SGLT1 short hairpin RNA (shRNA) or a scrambled RNA sequence. Subsequently, these rats underwent a hypoglycemic clamp to assess hormone responses. In a subgroup of rats, glucose kinetics was determined using tritiated glucose. The shRNA reduced VMH SGLT1 expression by 53% in nondiabetic rats, and this augmented glucagon and epinephrine responses and hepatic glucose production during hypoglycemia. Similarly, SGLT1 knockdown improved the glucagon and epinephrine responses in RH rats and restored the impaired epinephrine response to hypoglycemia in STZ-diabetic animals. These findings suggest that SGLT1 in the VMH plays a significant role in the detection and activation of counterregulatory responses to hypoglycemia. Inhibition of SGLT1 may offer a potential therapeutic target to diminish the risk of hypoglycemia in diabetes.
TL;DR: This is the first report using continuous blood glucose monitoring to show the benefits and lack of side effects of local anesthesia with epinephrine in patients with type 2 diabetes mellitus and coronary disease.
TL;DR: Patients with pseudopheochromocytoma appear to have an amplified cardiovascular responsiveness to catecholamines with enhanced sympathetic nervous stimulation, leading to differing hemodynamic presentations depending on whichcatecholamine is elevated.
TL;DR: Esmolol significantly alleviates postresuscitational autophagy, including mitophagy) and cardiomyocyte apoptosis in a rat CA model, suggesting that epinephrine/esmolol can attenuate postResuscitation antioxidation and apoptosis.
Abstract: BACKGROUND Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of postresuscitation myocardial dysfunction. The aim of this study was to investigate whether the short-acting β1-selective adrenergic blocking agent, esmolol, would impact postresuscitation autophagy and mitophagy in cardiomyocytes in a rat cardiac arrest (CA) model. METHODS CA was induced in Sprague Dawley rats by epicardial ventricular fibrillation for 5 minutes. After successful resuscitation, the surviving rats were randomly divided into 2 groups that received femoral venous injections of epinephrine combined with either esmolol (EE group) or epinephrine (E group). Arterial blood samples were obtained at times 0, 30, and 180 minutes after return of spontaneous circulation. Surviving rats were euthanatized at 12 or 24 hours after return of spontaneous circulation, and the hearts were removed for histochemical analysis, electron microscopy, Western blotting, and TUNEL experiment. RESULTS Relative to the E group, the EE group had reduced N-Methyl-D-Aspartate receptors expression and reduced arterial lactate levels (P < 0.05), suggesting that epinephrine/esmolol can attenuate postresuscitation antioxidation and apoptosis. This protective effect also correlated with a reduction of excessive autophagy and mitophagy in the cardiomyocytes, as evidenced by a reduction in Beclin-1 and Parkin expression (P < 0.05). CONCLUSIONS Esmolol significantly alleviates postresuscitational autophagy, including mitophagy, and cardiomyocyte apoptosis in a rat CA model.
TL;DR: Results indicated that baicalin acted on P2X3 receptor was involved in the transmission of sympathetic excitation after the myocardial ischemic injury, and Baicalin might decrease sympathetic activity via inhibiting P2x3 receptor in rat SCG to protect theMyocardium.
Abstract: After the myocardial ischemia, injured myocardial tissues released large quantity of ATP, which activated P2X3 receptor in superior cervical ganglia and made the SCG postganglionic neurons excited. Excitatory of sympathetic postganglionic efferent neurons increased the blood pressure and heart rates, which aggravated the myocardial ischemic injury. Baicalin has anti-inflammatory and anti-oxidant properties. Our study showed that baicalin reduced the incremental concentration of serum CK-MB, cTn-T, epinephrine and ATP, decreased the up-regulated expression levels of P2X3 mRNA and protein in SCG after MI, and then inhibited the sympathetic excitatory activity triggered by MI injury. These results indicated that baicalin acted on P2X3 receptor was involved in the transmission of sympathetic excitation after the myocardial ischemic injury. Baicalin might decrease sympathetic activity via inhibiting P2X3 receptor in rat SCG to protect the myocardium.
TL;DR: It is suggested that β2AR signaling is required for mucin production in response to IL-13, and that mitogen activated protein kinases and cAMP are necessary for this effect, and lend support to the notion thatβ2AR-agonists may contribute to asthma exacerbations by increasing mucinProduction via activation of β2 ARs on epithelial cells.
Abstract: Mucus hypersecretion by airway epithelium is a hallmark of inflammation in allergic asthma and results in airway narrowing and obstruction. Others have shown that administration a TH2 cytokine, IL-13 is sufficient to cause mucus hypersecretion in vivo and in vitro. Asthma therapy often utilizes β2-adrenoceptor (β2AR) agonists, which are effective acutely as bronchodilators, however chronic use may lead to a worsening of asthma symptoms. In this study, we asked whether β2AR signaling in normal human airway epithelial (NHBE) cells affected mucin production in response to IL-13. This cytokine markedly increased mucin production, but only in the presence of epinephrine. Mucin production was blocked by ICI-118,551, a preferential β2AR antagonist, but not by CGP-20712A, a preferential β1AR antagonist. Constitutive β2AR activity was not sufficient for IL-13 induced mucin production and β-agonist-induced signaling is required. A clinically important long-acting β-agonist, formoterol, was as effective as epinephrine in potentiating IL-13 induced MUC5AC transcription. IL-13 induced mucin production in the presence of epinephrine was significantly reduced by treatment with selective inhibitors of ERK1/2 (FR180204), p38 (SB203580) and JNK (SP600125). Replacement of epinephrine with forskolin + IBMX resulted in a marked increase in mucin production in NHBE cells in response to IL-13, and treatment with the inhibitory cAMP analogue Rp-cAMPS decreased mucin levels induced by epinephrine + IL-13. Our findings suggest that β2AR signaling is required for mucin production in response to IL-13, and that mitogen activated protein kinases and cAMP are necessary for this effect. These data lend support to the notion that β2AR-agonists may contribute to asthma exacerbations by increasing mucin production via activation of β2ARs on epithelial cells.
TL;DR: In this paper, isolated rat myocardial cells were incubated with the radioactive β-adrenoceptor ligand [ 3 H]-CGP12177 and propranolol, used as a displacer.
TL;DR: The data indicate that afferent pathways of the vagus nerve are involved in negative feedback regulation of epinephrine secretion from the adrenal medulla during stressful conditions and hypothesize that this feedback mechanism might be mediated by the binding of circulating epinphrine on β2-adrenergic receptors localized on sensory endings of thevagus nerve.
Abstract: Neuroendocrine stress response is regulated by several feedback loops. Since it has been suggested that afferent vagal pathways contribute to these feedback loops, we examined the effect of surgical subdiaphragmatic vagotomy on both baseline and stress-induced increases in plasma epinephrine, norepinephrine, and corticosterone levels in vagotomized and sham-operated Sprague Dawley rats. On either the 3rd or 14th day following vagotomy, the animals were exposed to acute immobilization stress and blood from the jugular vein was collected both before and during stress exposure. We found that vagotomy significantly enhanced immobilization-induced increases of plasma epinephrine, norepinephrine, and corticosterone levels on the 3rd day following surgery. However, on the 14th day following surgery, vagotomy enhanced only increase of plasma epinephrine levels in stressed rats. Our data indicate that afferent pathways of the vagus nerve are involved in negative feedback regulation of epinephrine secretion from the adrenal medulla during stressful conditions. We hypothesize that this feedback mechanism might be mediated by the binding of circulating epinephrine on β2-adrenergic receptors localized on sensory endings of the vagus nerve.
TL;DR: Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with diabetes mellitus and liver disease, with no significant correlation seen for cholinergic function.
TL;DR: A deep level of anesthesia achieved using high propofol infusion rates during lung surgery provided lower perioperative norepinephrine and glucose responses than lightlevel of anesthesia during the early postoperative period but failed to affect immediate postoperative outcomes.
Abstract: Background This prospective, randomized controlled study was undertaken to compare stress hormone response to open thoracotomy for lung resection at different anesthetic depths, as determined by bispectral index (BIS) monitoring, in patients under propofol-remifentanil anesthesia. Methods Forty-eight adult patients scheduled for lung resection surgery using one-lung ventilation were randomly assigned to either a deep anesthesia group (BIS score of 40 ± 5, n = 24) or a light anesthesia group (BIS score of 60 ± 5, n = 24) by adjusting propofol infusion rates. Blood norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol levels were measured before the induction of anesthesia, at the end of surgery, and at 2 hours postoperatively. Blood glucose, hemodynamic, and oxygenation-ventilation variables, and postoperative outcomes were also measured. Results Norepinephrine and epinephrine levels remained unchanged over time in the deep group, but norepinephrine levels significantly increased in the light group at 2 h after surgery than at baseline (P = 0.007 and 0.004, respectively). Temporal changes in norepinephrine, but not in epinephrine, were significantly different between the two groups (P = 0.036). Plasma glucose levels in the light group increased with time and were significantly higher than in the deep group at the end of surgery (P = 0.002). Conclusions A deep level of anesthesia achieved using high propofol infusion rates during lung surgery provided lower perioperative norepinephrine and glucose responses than light level of anesthesia during the early postoperative period but failed to affect immediate postoperative outcomes.
TL;DR: The β- and β- plus α1-blocker pretreatment significantly reduced the severity of PR myocardial tissue injury and myocardIAL dysfunction with better neurologic function and prolonged duration of survival.
TL;DR: In this paper, the authors measured epinephrine and cAMP levels using ELISA techniques and found that the lowest dose (0.05-0.5mcgkg −1 min −1 ) did not raise plasma epinegon levels and did not lead to cardiovascular response.
Abstract: Background While epinephrine infusion is widely used in critical care for inotropic support, there is no direct method to detect the onset and measure the magnitude of this response. We hypothesised that surrogate measurements, such as heart rate and vascular tone, may indicate if the plasma and tissue concentrations of epinephrine and cAMP are in a range sufficient to increase myocardial contractility. Methods Cardiovascular responses to epinephrine infusion (0.05-0.5mcgkg −1 min −1 ) were measured in rats using arterial and left ventricular catheters. Epinephrine and cAMP levels were measured using ELISA techniques. Results The lowest dose of epinephrine infusion (0.05mcgkg −1 min −1 ) did not raise plasma epinephrine levels and did not lead to cardiovascular response. Incremental increase in epinephrine infusion (0.1mcgkg −1 min −1 ) elevated plasma but not myocardial epinephrine levels, providing vascular, but not cardiac effects. Further increase in the infusion rate (0.2mcgkg −1 min −1 ) raised myocardial tissue epinephrine levels sufficient to increase heart rate but not contractility. Inotropic and lusitropic effects were significant at the infusion rate of 0.3mcgkg −1 min −1 . Correlation of plasma epinephrine to haemodynamic parameters suggest that as plasma concentration increases, systemic vascular resistance falls (EC50=47 pg/ml), then HR increases (ED50=168 pg/ml), followed by a rise in contractility and lusitropy (ED50=346 pg/ml and ED50=324 pg/ml accordingly). Conclusions The dose response of epinephrine is distinct for vascular tone, HR and contractility. The need for higher doses to see cardiac effects is likely due to the threshold for drug accumulation in tissue. Successful inotropic support with epinephrine cannot be achieved unless the infusion is sufficient to raise the heart rate.
TL;DR: It is demonstrated that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia, and the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release was compromised.
Abstract: In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia.