Showing papers on "Epinephrine published in 2001"
TL;DR: A prospective, randomized, blinded, placebo-controlled, 6-way crossover study of intramuscular versus subcutaneous injection of epinephrine in young men was conducted in this paper.
Abstract: We report a prospective, randomized, blinded, placebo-controlled, 6-way crossover study of intramuscular versus subcutaneous injection of epinephrine in young men. Peak plasma epinephrine concentrations were significantly higher (P < .01) after epinephrine was injected intramuscularly into the thigh than after epinephrine was injected intramuscularly or subcutaneously into the upper arm. We recommend intramuscular injection of epinephrine into the thigh as the preferred route and site of injection of this life-saving medication in the initial treatment of anaphylaxis. (J Allergy Clin Immunol 2001;108:871-3.)
441 citations
TL;DR: A triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals failed to detect any survival advantage for vasopressin over epinephrine, and cannot recommend the routine use of vasopressing for inhospital cardiac arrest patients.
310 citations
TL;DR: The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions and lesions are more frequent in the zona fasciculata and reticularis than in theZona glomerulosa; Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis.
Abstract: The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and endoplasmic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds, natural and synthetic steroids, and chemicals that affect hydroxylation. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneration (vacuolar and granular), necrosis, and hemorrhage are common findings of acute injury. In contrast, chronic reparative processes are typically atrophy, fibrosis, and nodular hyperplasia. Chemically induced proliferative lesions are uncommon in the adrenal cortex. The adrenal medulla contains chromaffin cells (that produce epinephrine, norepinephrine, chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochromocytoma. Mechanisms of chromaffin cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcemia. There often are species specificity and age dependence in the development of chemically induced adrenal lesions that should be considered when interpreting toxicity data.
219 citations
TL;DR: The combined report of low-frequency BPV and PEP gives distinct information on both central SNS control and the level of sympathetic cardiac activation achieved, providing empirical evidence of separable peripheral and central sympathetic response components.
Abstract: OBJECTIVE A number of sympathetic nervous system (SNS) parameters have been used in cardiovascular psychophysiology. This study aimed to describe the pattern and redundancy of a set of SNS parameters during peripherally induced changes of cardiac sympathetic activation and reflex modulation of central SNS control. Preejection period (PEP) was assessed as a marker of peripheral sympathetic activation. Low-frequency blood pressure variability (BPV) was assessed as an estimate of central SNS control. METHODS Peripheral beta-sympathetic stimulation and blockade were achieved with epinephrine and esmolol hydrochloride (beta1-blockade), respectively. Changes in central SNS output were induced by loading and unloading arterial baroreceptors with norepinephrine and nitroprusside sodium, respectively. This single-blinded, crossover study in 24 healthy men also included two placebo control periods. PEP was derived from impedance cardiography and adjusted individually for heart rate. BPV was calculated by power spectral analyses of beat-to-beat heart rate and systolic blood pressure (Finapres system) data. RESULTS PEP decreased during epinephrine infusion (-40.1 +/- 3.8 ms, p <.0001) and increased during esmolol infusion (+6.6 +/- 3.5 ms, p =.05). PEP was shortened after central SNS activation by nitroprusside (-16.8 +/- 2.9 ms, p < 0.0001). Systolic BPV in the low-frequency range (0.07-0.14 Hz, Mayer waves) increased during nitroprusside infusion (+0.44 +/- 0.19 ln mm Hg(2), p =.03) and decreased during norepinephrine infusion (-0.67 +/- 0.13 ln mm Hg(2), p < 0.0001). Low-frequency BPV did not change significantly during epinephrine or esmolol infusion. CONCLUSIONS Our data provide empirical evidence of separable peripheral and central sympathetic response components. The combined report of low-frequency BPV and PEP gives distinct information on both central SNS control and the level of sympathetic cardiac activation achieved.
169 citations
TL;DR: A therapeutic trial with hydrocortisone should be started in patients with suspected adrenal insufficiency pending results of diagnostic testing.
158 citations
TL;DR: Epinephrine combined with vasopressin, but not epinephrine or vasopressingin alone, maintained elevated coronary perfusion pressure during cardiopulmonary resuscitation and resulted in significantly higher survival rates in this adult porcine asphyxial model.
Abstract: Background The purpose of this study was to investigate the effects of vasopressin versus epinephrine, and both drugs combined, in a porcine model of simulated adult asphyxial cardiac arrest. Methods and Results At ≈7 minutes after the endotracheal tube had been clamped, cardiac arrest was present in 24 pigs and remained untreated for another 8 minutes. After 4 minutes of basic life support cardiopulmonary resuscitation, pigs were randomly assigned to receive, every 5 minutes, either epinephrine (45, 200, or 200 μg/kg; n=6); vasopressin (0.4, 0.8, or 0.8 U/kg; n=6); or epinephrine combined with vasopressin (high-dose epinephrine/vasopressin combination, μg/kg and U/kg: 45/0.4, 200/0.8, or 200/0.8; n=6; optimal-dose epinephrine/vasopressin combination, 45/0.4, 45/0.8, or 45/0.8; n=6). Mean±SEM coronary perfusion pressure was significantly (P<0.05) higher 90 seconds after high- or optimal-dose epinephrine/vasopressin combinations versus vasopressin alone and versus epinephrine alone (37±10 versus 25±7 versu...
121 citations
TL;DR: It is shown that leptin transport into the brain is enhanced 2–3-fold by epinephrine and other agents which are more specific for the α1 adrenergic receptor, andEpinephrine works at an α1-like adrenergic, luminal side to enhance the transport of leptin across the BBB.
118 citations
TL;DR: These data demonstrate a nearly complete requirement of endogenous norepinephrine and epinephrine for the induction of in vivo pressure-overload cardiac hypertrophy and for the activation of hypertrophic signaling pathways.
117 citations
TL;DR: It is suggested that intracerebroventricular orexin-A acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.
Abstract: —We determined the cardiovascular and neurohormonal responses to intracerebroventricular administration of orexin-A in conscious rabbits. Intracerebroventricular injection of orexin-A elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 100 pmol of orexin-A (14.0±0.7 mm Hg and 55.4±14.9%, respectively) were obtained at 40 and 25 minutes after injection, respectively. Plasma epinephrine and glucose concentrations were significantly increased at 60 and 90 minutes after intracerebroventricular injection of orexin-A (control versus 90 minutes; for epinephrine, 38.0±12.8 versus 167.5±42.5 pg/mL, P P
116 citations
Journal Article•
TL;DR: Epinephrine injection prior to polypectomy is effective in preventing immediate bleeding and there was no significant difference in clinical features including the sizes of the polyps and their stalks, the location ofpolyps and the pathological diagnosis.
Abstract: Background/aims Polyps of the gastrointestinal tract are usually removed due to their link to bleeding, obstruction and malignancy. However, complications may occur following polypectomy. The aim of this study was to assess whether submucosal epinephrine injection before polypectomy could reduce the incidence of bleeding and perforation. Methodology Between June 1997 and November 1999, patients with sessile polyps of the gastrointestinal tract found in our endoscopic unit were randomized to receive submucosal epinephrine injection (epinephrine group) or no injection (control group) before polypectomy. In the epinephrine group, epinephrine (1:10,000) was injected surrounding the stalk of the polyp until the mucosa was blanched and bulged. The patients were observed for complications in the following month. Results A total of 120 patients with 151 sessile polyps were enrolled in this study. In the epinephrine group, 75 polyps (n = 68) were randomized to receive epinephrine injection before polypectomy. In the control group, 76 polyps (n = 61) underwent polypectomy without epinephrine injection. In both groups, there was no significant difference in clinical features including the sizes of the polyps and their stalks, the location of polyps and the pathological diagnosis. There were a total of nine episodes of post-polypectomy hemorrhage, two in the epinephrine group and seven in the control group (2/75 vs. 7/76) (P = 0.07). One case in the epinephrine group experienced delayed bleeding (4 days later). Immediate hemorrhage occurred less in the epinephrine group than that in the control group (1/75 vs. 7/76, P = 0.03). There was one case of perforation in each group. Conclusions Epinephrine injection prior to polypectomy is effective in preventing immediate bleeding.
102 citations
TL;DR: It was concluded that atrophy and hypertrophy both decrease insulin responsiveness and shift myocardial substrate preference to glucose, consistent with a shift to a fetal pattern of energy consumption and that the isoform-specific changes that develop in vivo do not change the regulation of key metabolic enzymes when assayed in vitro.
Abstract: It has been observed that opposite changes in cardiac workload result in similar changes in cardiac gene expression. In the current study, the hypothesis that altered gene expression in vivo results in altered substrate fluxes in vitro was tested. Hearts were perfused for 60 minutes with Krebs-Henseleit buffer containing glucose (5 mmol/L) and oleate (0.4 mmol/L). At 30 minutes, either insulin (1 mU/mL) or epinephrine (1 micromol/L) was added. Hearts weighed 35% less after unloading and 25% more after aortic banding. Contractile function in vitro was decreased in transplanted and unchanged in banded hearts. Epinephrine, but not insulin, increased cardiac power. Basal glucose oxidation was initially decreased and then increased by aortic banding. The stimulatory effects of insulin or epinephrine on glucose oxidation were reduced or abolished by unloading, and transiently reduced by banding. Oleate oxidation correlated with cardiac power both before and after stimulation with epinephrine, whereas glucose oxidation correlated only after stimulation. Malonyl-coenzyme A levels did not correlate with rates of fatty acid oxidation. Pyruvate dehydrogenase was not affected by banding or unloading. It was concluded that atrophy and hypertrophy both decrease insulin responsiveness and shift myocardial substrate preference to glucose, consistent with a shift to a fetal pattern of energy consumption; and that the isoform-specific changes that develop in vivo do not change the regulation of key metabolic enzymes when assayed in vitro.
TL;DR: Comparison of the data with the predictions of a previously developed recirculatory model of prop ofol disposition in sheep showed the data were consistent with a mechanism based on increased first pass dilution and clearance of propofol secondary to the increased cardiac output, either induced by exogenous catecholamine infusions or pathological states.
Abstract: Objective: To determine the effects of exogenous ramped infusions of epinephrine, norepinephrine and dopamine on arterial and effluent brain blood concentrations of propofol under steady state intravenous anesthesia. Design: Prospective, randomized animal study. Setting: University research laboratory. Subjects: Five adult female merino sheep. Interventions: Induction (5 mg/kg) and continuous infusion of propofol (15 mg/min) with controlled mechanical ventilation to maintain PaCO2 40 mmHg. After 1 h of continuous anesthesia, each animal randomly received ramped infusions of epinephrine, norepinephrine (10, 20, 40 µg/min) and dopamine (10, 20, 40 µg·kg·min) in 3×5 min intervals followed by a 30-min washout period. Measurements: Arterial and sagittal sinus whole blood for determination of propofol concentrations using high-pressure liquid chromatography. Cardiac output using a thermodilution method. Level of consciousness using an observational scale. Main results: All three drugs significantly and transiently increased cardiac output in a dose-dependent fashion to a maximum of 146–169% of baseline. Baseline arterial and sagittal sinus propofol concentrations were not statistically different prior to catecholamine infusions. All three drugs significantly reduced mean arterial propofol concentrations (95% CI, p<0.05): epinephrine to 41.8% of baseline (11.4–72), norepinephrine to 63% (27–99) and dopamine to 52.9% (18.5–87.3). There were parallel reductions of concentrations in sagittal sinus blood leaving the brain. The lowest blood concentrations were associated with emergence from anesthesia. Arterial concentrations were inversely related to the simultaneously determined cardiac output (r2=0.74, p<0.0001). Comparison of the data with the predictions of a previously developed recirculatory model of propofol disposition in sheep showed the data were consistent with a mechanism based on increased first pass dilution and clearance of propofol secondary to the increased cardiac output. Conclusions: Catecholamines produced circulatory changes that reversed propofol anesthesia. These observations have potential clinical implications for the use of propofol in hyperdynamic circulatory conditions, either induced by exogenous catecholamine infusions or pathological states.
TL;DR: The data suggest that catecholamines secreted by the adrenal medulla exert an inhibitory control of Ca(2+)-dependent proteolysis in rat skeletal muscle, mediated by beta(2)-adrenoceptors, with the participation of a cAMP-dependent pathway.
Abstract: Overall proteolysis and the activity of skeletal muscle proteolytic systems were investigated in rats 1, 2, or 4 days after adrenodemedullation. Adrenodemedullation reduced plasma epinephrine by 95...
TL;DR: Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model, and dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation.
Abstract: The most appropriate inotropic agent for use in the newborn is uncertain. Dopamine and epinephrine are commonly used, but have unknown effects during hypoxia and pulmonary hypertension; the effects on the splanchnic circulation, in particular, are unclear. The effects on the systemic, pulmonary, hepatic, and mesenteric circulations of infusions of dopamine and epinephrine (adrenaline) were compared in 17 newborn piglets. Three groups [control (n = 5), dopamine (n = 6) and epinephrine (n = 6)] of fentanyl anesthetized newborn piglets were instrumented to measure cardiac index (CI), hepatic arterial and portal venous blood flow, mean systemic arterial pressure (SAP), mean pulmonary arterial pressure (PAP), and arterial, portal and mixed venous oxygen saturations. Systemic, pulmonary, and mesenteric vascular resistance indices [systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), mesenteric vascular resistance index (MVRI)], and systemic and splanchnic oxygen extraction and consumption were calculated. Alveolar hypoxia was induced, with arterial oxygen saturation being maintained at 55-65%. After 1 h of stabilization during hypoxia, each animal received either dopamine or epinephrine; randomly administered doses of 2, 10, and 32 μg kg-1 min-1 and 0.2, 1.0, and 3.2 μg kg-1 min-1 respectively were infused for 1 h at each dose. Results were compared with the 1 h hypoxia values by two-way analysis of variance. Epinephrine increased CI at all doses, with no significant effects on SAP and SVRI. Although epinephrine increased PAP at 3.2 μg kg-1min-1, it had no effect on PVRI. Dopamine had no effect on CI, SAP, and SVRI, but increased PAP at all doses and PVRI at 32 μg kg-1min-1. The SAP/PAP ratio was decreased with 32 μg kg-1min-1 dopamine, whereas epinephrine did not affect the ratio. In the mesenteric circulation, dopamine at 32 μg kg-1 min-1 increased portal venous flow and total hepatic blood flow and oxygen delivery, and decreased MVRI; epinephrine had no effect on these variables. Epinephrine increased hepatic arterial flow at 0.2 μg kg-1 min-1; dopamine had no effect on hepatic arterial flow at any dose. Despite these hemodynamic changes, there were no differences in systemic or splanchnic oxygen extraction or consumption at any dose of dopamine or epinephrine. Epinephrine is more effective than dopamine at increasing cardiac output during hypoxia in this model. Although epinephrine preserves the SAP/PAP ratio, dopamine shows preferential pulmonary vasoconstriction, which might be detrimental if it also occurs during the management of infants with persistent fetal circulation. Dopamine, but not epinephrine, increases portal flow and total hepatic flow during hypoxia.
TL;DR: It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response.
Abstract: Glucocorticoids are required for the normal functioning of chromaffin cells and their capacity to produce epinephrine. This was modeled in a unique clinical syndrome of isolated glucocorticoid deficiency due to unresponsiveness to ACTH. The working hypotheses were that in patients with isolated glucocorticoid deficiency, adrenomedullary epinephrine would be suppressed despite replacement therapy; that norepinephrine might show a compensatory response; and that the physiological response to stress would reflect these changes. Toward these hypotheses, patients with ACTH unresponsiveness on glucocorticoid replacement were subjected to three levels of acute stress: assumption of upright posture, cold pressor, and exercise. Their catecholamine and physiological response were monitored. Patients with isolated glucocorticoid deficiency of this study had severe adrenomedullary dysfunction, characterized by a minimal resting production of epinephrine (6 +/- 2 pg/ml compared with 64 +/- 22 pg/ml of the controls) and a minimal response to stress. A slight compensatory increase of norepinephrine was found in response to cold pressor test (754 +/- 200 pg/ml compared with 431 +/- 73 pg/ml of the control). The physiological response is characterized by low systolic blood pressure and high pulse rate in rest and mild stress and in a pressor response to exercise (diastolic 87 +/- 5 mm Hg, compared with 73 +/- 2 mm Hg of the control). It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response. The implications of the pressor response to exercise, the declining pulse pressure, and the increased pulse response insinuate a lower physical fitness in patients with adrenal insufficiency.
TL;DR: Neither hypoxia nor defective oxidative metabolism appeared responsible for increased glycolysis during hemorrhagic shock, and rapid skeletal muscle aerobic glycoleysis in response to increased plasma epinephrine levels may be an important contributor to increased gly colysis in muscle and increased plasma lactate during bleed.
TL;DR: The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine, and when making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epine cortisol.
Abstract: Background Epinephrine is commonly added to lidocaine solutions to increase the duration of spinal anesthesia. Despite this common usage, the effect of epinephrine on the neurotoxic potential of this anesthetic is not known. The current experiments investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. Methods Eighty rats were divided into four groups to receive an intrathecal injection of normal saline containing either 5% lidocaine, 5% lidocaine with 0.2 mg/ml of epinephrine, 0.2 mg/ml of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail-flick test administered 4 and 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. Results Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. Conclusions The neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine.
TL;DR: In the CPR laboratory simulating adult pigs with ventricular fibrillation or postcountershock pulseless electrical activity, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurological recovery better than did epinephrine, which may suggest that a different efficiency of vasopressed in paediatric vs. adult preparations; and different effects of dysrhythmic vs. asphyxial cardiac arrest on vasopressor efficiency may be of significant importance.
Abstract: Epinephrine during cardiopulmonary resuscitation (CPR) is being discussed controversially due to its beta-receptor mediated adverse effects such as increased myocardial oxygen consumption, ventricular arrhythmias, ventilation-perfusion defect, postresuscitation myocardial dysfunction, ventricular arrhythmias and cardiac failure. In the CPR laboratory simulating adult pigs with ventricular fibrillation or postcountershock pulseless electrical activity, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurological recovery better than did epinephrine. In paediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both paediatric pigs with ventricular fibrillation, and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. This may suggest that a different efficiency of vasopressors in paediatric vs. adult preparations; and different effects of dysrhythmic vs. asphyxial cardiac arrest on vasopressor efficiency may be of significant importance. Whether these theories can be extrapolated to humans is unknown at this point in time. In patients with out-of-hospital ventricular fibrillation, a larger proportion of patients treated with vasopressin survived 24 h compared with patients treated with epinephrine; during in-hospital CPR, comparable short-term survival was found in groups treated with either vasopressin or epinephrine. Currently, a large trial of out-of-hospital cardiac arrest patients being treated with vasopressin vs. epinephrine is ongoing in Germany, Austria and Switzerland. The new CPR guidelines of both the American Heart Association, and European Resuscitation Council recommend 40 U vasopressin intravenously, and 1 mg epinephrine intravenously as equally effective for the treatment of adult patients in ventricular fibrillation; however, no recommendation for vasopressin was made to date for adult patients with asystole and pulseless electrical activity, and paediatrics due to lack of clinical data. When adrenergic vasopressors were unable to maintain arterial blood pressure in patients with vasodilatory shock, continuous infusions of vasopressin ( approximately 0.04 to approximately 0.1 U/min) stabilised cardiocirculatory parameters, and even ensured weaning from catecholamines.
Patent•
03 Apr 2001TL;DR: In this article, a cardiovascular and respiratory stimulating composition for administration to a patient in doses, the composition comprising a pharmacologically effective concentration of (+)naloxone in a carrier solution.
Abstract: A composition formulated for dose-wise delivery to a breathing passageway of a human, the composition comprising a carrier solution containing (+)naloxone and a pharmacologically effective amount of at least one adrenergic agonist, the (+)naloxone and agonist forming a mixture in the carrier. The at least one adrenergic agonist is selected from the group consisting of epinephrine, isoproterenol, abluterol, aminophyline, beclomethasone, dyphylline, flunisolide, isoetharine, metaproterenol, oxtriphylline terbutaline, theophylline, pseudoephedrine, phenylephrine, ephedrine and norepinephrine. That composition is delivered by an atomizer means such as a liquid sprayer or inhaler to treat nasal congestion and asthmatic attacks. Further provided by the invention is a cardiovascular and respiratory stimulating composition for administration to a patient in doses, the composition comprising a pharmacologically effective concentration of (+)naloxone in a carrier solution. If necessary, the composition may also contain a pharmacologically effective amount of at least one adrenergic agonist.
TL;DR: After a short 4-min period of hypothermic cardiac arrest, epinephrine may not be necessary to maintain coronary perfusion pressure around the threshold usually correlating with successful defibrillation, even during prolonged closed-chest CPR combined with active rewarming.
TL;DR: The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.
TL;DR: Results suggested that catecholamines up‐regulate UCP2 and UCP3 expression through direct action on the β2‐AR in skeletal muscle.
TL;DR: The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor‐mediated inhibition of acetylcholine release from preganglionic sympathetic neurons.
Abstract: The objective of the present study was to analyse the peripheral effects of cannabinoids on adrenaline release from adrenal chromaffin cells.
In pithed rabbits with electrically stimulated sympathetic outflow, intravenous injection of the cannabinoid receptor agonists WIN55212-2 and CP55940 (5, 50 and 500 μg kg−1) markedly lowered the plasma adrenaline concentration. The effect of WIN55212-2 was attenuated by the selective CB1 cannabinoid receptor antagonist SR141716A (500 μg kg−1). WIN55212-3 (same doses as WIN55212-2), the enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, had no effect on the plasma adrenaline concentration.
In rabbit isolated adrenal glands, the release of adrenaline elicited by electrical stimulation was measured by fast cyclic voltammetry. Electrically-evoked adrenaline release was inhibited by WIN55212-2 (0.3, 1, 3 and 10 μM) and this effect was antagonized by SR141716A (1 μM). The non-cholinergic component of adrenaline release observed after blockade of nicotinic (by hexamethonium 100 μM) and muscarinic (by atropine 0.5 μM) acetylcholine receptors was not depressed by WIN55212-2. WIN55212-3 (10 μM) had no effect on adrenaline release.
No detectable specific CB1 receptor binding and mRNA expression were found in rabbit adrenal glands with autoradiography and in situ hybridization.
The results show that cannabinoids inhibit adrenaline secretion in rabbit isolated adrenal glands; the likely mechanism is a presynaptic CB1 receptor-mediated inhibition of acetylcholine release from preganglionic sympathetic neurons. The inhibition of adrenaline secretion in adrenal glands most probably accounts for the decrease in the plasma adrenaline concentration observed after cannabinoid administration in pithed rabbits.
British Journal of Pharmacology (2001) 134, 1319–1327; doi:10.1038/sj.bjp.0704359
TL;DR: Results suggest that plasma epinephrine and norepinephrine can be used as a measure for cocaine induced sympathoadrenal system activation, in a double-blind, placebo-controlled study.
Abstract: Cocaine has been shown to activate the sympathoadrenal system in both animal and human studies. Controlled human studies have found inconclusive results regarding whether acute cocaine treatment elevates plasma epinephrine and norepinephrine concentrations. The purpose of this study was to investigate whether commonly abused doses of cocaine increase plasma epinephrine and norepinephrine concentrations in humans, in a double-blind, placebo-controlled study. Five male cocaine users were given an intravenous injection of 0.46 mg/kg dose of cocaine or placebo, on two consecutive days. Plasma epinephrine and norepinephrine concentrations were significantly increased in response to cocaine injection compared to placebo. Peak plasma epinephrine and norepinephrine concentrations were reached 3 and 12 min after cocaine injection, respectively. While changes in epinephrine levels following cocaine were correlated with systolic blood pressure and heart rate changes, changes in plasma norepinephrine were correlated with diastolic blood pressure and heart rate changes following cocaine administration. These results suggest that plasma epinephrine and norepinephrine can be used as a measure for cocaine induced sympathoadrenal system activation.
TL;DR: Surprisingly L-arginine was as effective as L-NNA and increased the chronotropic effect of epinephrine in cholestatic rats but not in sham-operated animals, and suggests an important role for NO in the pathophysiology of heart rate complications in cholinergic subjects.
Journal Article•
TL;DR: The anaesthesiological management may have considerable influence on the postoperative inflammatory process, and induction of the release of anti-inflammatory mediators under TIVA might contribute to the prevention of excessive postoperative inflammation.
Abstract: The modulation of immune functions, induced by trauma, surgical interventions and anaesthesia, is thought to play a crucial role in the development of post-traumatical or postoperative disorders. The balance of pro- and anti-inflammatory cytokines was shown to affect the outcome of the patients. This work studied the effects of different anaesthesiological procedures--total intravenous anaesthesia using Propofol/Sufentanil (TIVA) versus balanced inhalational anaesthesia using Trapanal/Sevoflurane (BIA) in patients with elective lumbal discectomia--on the secretion of various cytokines and their correlation to endocrine stress response. The concentrations of the pro-inflammatory cytokines IL-2, IL-6, IL-12 and IFN-gamma and their soluble receptor molecules as well as the concentrations of the anti-inflammatory cytokines IL-10, IL-1RA and TGF-beta were determined in plasma samples obtained pre-, intra- and postoperatively. Additionally, the plasma concentrations of the stress-related hormones cortisol, epinephrine and norepinephrine were measured. Changes in the cytokine profile were observed immediately after induction of anaesthesia. Significant differences were found particularly in IL-6 production as well as in the release of the soluble IL-2R alpha and the IL-1 receptor antagonist (IL-1RA). Whereas under BIA, the concentrations of IL-6 were found to be significantly elevated during the course of the study, the release of the soluble IL-2R alpha and the production of IL-1RA were reduced in this patient group in comparison to the TIVA group. The increase of the postoperative concentrations of cortisol, epinephrine and norepinephrine under BIA indicated enhanced activation of the hypothalamo-pituitary-adrenal axis and the sympathetic system. Thus, with respect to limitation of surgery-associated stress, total intravenous anaesthesia seems to have a favourable effect. Moreover, induction of the release of anti-inflammatory mediators under TIVA might contribute to the prevention of excessive postoperative inflammation. Taken together, these data suggest that the anaesthesiological management may have considerable influence on the postoperative inflammatory process. This might be of particular relevance for surgical interventions in patients after injuries, infections or malignant diseases which are known to be associated with immune dysfunction.
TL;DR: Epinephrine in concentrations of 1:100,000 and 1:200,000 causes significant hypertension and the combination of lidocaine and epinephrine attenuates the hypertension but results in a biphasic hypotensive response.
Abstract: Intraoperative blood pressure changes alter cerebral blood flow in neurosurgical patients with impaired autoregulation. Infiltration of the scalp before craniotomy may cause hemodynamic changes that depend on the composition of the solution used. We investigated cardiovascular responses to infiltration of the scalp with five different combinations of epinephrine and lidocaine in 112 patients: Group A, lidocaine 0.5%; Group B, lidocaine 0.5% with epinephrine 1:200,000; Group C, lidocaine 0.5% with epinephrine 1:100,000; Group D, normal saline with epinephrine 1:200,000; and Group E, normal saline with epinephrine 1:100,000. Episodes of tachycardia occurred more frequently in group E (P = 0.03). Plain lidocaine did not cause any significant change in blood pressure. The incidence of systolic, diastolic, and mean arterial hypertension was significantly increased in group E (P < 0.01). Episodes of diastolic hypertension occurred more frequently in Group D (P < 0.01). A biphasic diastolic and mean arterial hypotension (around Minute 2 and Minutes 9-15) occurred in Groups C and B (P < 0.001). In conclusion, epinephrine 1:100,000 causes significant tachycardia. Epinephrine in concentrations of 1:100,000 and 1:200,000 causes significant hypertension. The combination of lidocaine and epinephrine attenuates the hypertension but results in a biphasic hypotensive response.
TL;DR: In the CPR laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurologic recovery more than did epinephrine in patients with out-of-hospital ventricular fibrillation.
Abstract: Epinephrine use during cardiopulmonary resuscitation (CPR) is controversial because of its receptor-mediated adverse effects such as increased myocardial oxygen consumption, ventricular arrhythmias, ventilation-perfusion defect, postresuscitation myocardial dysfunction, ventricular arrhythmias, and cardiac failure. In the CPR laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurologic recovery more than did epinephrine. In patients with out-of-hospital ventricular fibrillation, a larger proportion of patients treated with vasopressin survived 24 hours than did patients treated with epinephrine. Currently, a large trial of out-of-hospital cardiac arrest patients being treated with vasopressin versus epinephrine is ongoing in Germany, Austria, and Switzerland. The new international CPR guidelines recommend 40 U vasopressin intravenously, and 1 mg epinephrine intravenously, as equally effective for the treatment of adult patients in ventricular fibrillation; however, no recommendation for vasopressin has been made to date for adult patients with asystole and pulseless electrical activity, or in children, because of lack of clinical data. When adrenergic vasopressors were unable to maintain arterial blood pressure in patients with vasodilatory shock, continuous infusions of vasopressin (0.04-0.10 U/min) stabilized cardiocirculatory parameters and even ensured weaning from catecholamines.
TL;DR: Exogenously administered ANG II increases the amount of NE liberated into the ISF independent of the adrenal contribution, the amount matching that induced by electrical stimulation of all cardiac sympathetic efferent neurons.
Abstract: This study tested the hypothesis that exogenous infusion of angiotensin II (ANG II) leads to the release of catecholamines [norepinephrine (NE) and epinephrine (EPI)] into the cardiac interstitial ...
TL;DR: It is concluded that one bolus of an extremely dilute concentration of epinephrine (i.e., 1:400,000) injection might be effective in maintaining mydriasis during cataract surgery without systemic side effects.
Abstract: Surgically-induced miosis commonly occurs during cataract extraction surgery, complicating removal of lens cortex and placement of a posterior chamber intraocular lens. To maintain intraoperative mydriasis, one bolus of epinephrine injection was used in our study. The pupillary response to various doses of intracameral epinephrine (0.1 ml of 1:25,000, 1:50,000, 1:100,000, 1:200,000, 1:400,000) was assessed in 60 consecutive patients. The pupil size was measured just prior to the incision, one min after epinephrine injection, after phacoemulsification and after irrigation/aspiration. There was no significant difference among the mean mydriatic responses to the epinephrine concentrations we tested. The 1:400,000 concentration appeared to be as effective as 1:25,000, but two cases of the 1:400,000 group failed to maintain the pupil diameter after irrigation/aspiration. In addition, we found that blood pressure did not elevate after injection of any concentration of epinephrine. We concluded that one bolus of an extremely dilute concentration of epinephrine (i.e., 1:400,000) injection might be effective in maintaining mydriasis during cataract surgery without systemic side effects.