Showing papers on "Epinephrine published in 1998"

Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action

Abstract: The beta-adrenergic receptors (beta-AR) are present on the surface of almost every type of mammalian cell. These receptors are stimulated physiologically by the neurotransmitter, norepinephrine and the adrenal medullary hormone, epinephrine. There are three subtypes of beta-AR, namely, beta1-AR, beta2-AR, and beta3-AR; the pharmacological and physiological responses of an individual cell result from the particular mixture of the three beta-AR subtypes present on that cell. Species-specific structure (amino acid sequence) also causes modification of the function of a given beta-AR subtype. Knowledge of the beta-AR subtypes present in various cell types, coupled with knowledge of receptor structure (sequence), will allow an understanding of the complexity of physiological function regulated by beta-AR. Oral administration of some beta-AR agonists increases muscle and decreases fat accretion in cattle, pigs, poultry, and sheep. The large number of physiological functions controlled by beta-AR suggests that the mechanism(s) for the observed changes in carcass composition may be extremely complex. Any proposed mechanism must begin with the possibility of direct effects of the agonist on skeletal muscle and adipocyte beta-AR. However, many other mechanisms, such as modification of blood flow, release of hormones, or central nervous system control of feed intake may contribute to the overall effects observed with a given beta-AR agonist in a given species. Furthermore, the pharmacodynamic properties of a particular agonist are complex and expected to vary among species as well as within the same species at different ages or when fed different diets.

Epinephrine absorption in children with a history of anaphylaxis

Abstract: Background: Prompt injection of epinephrine is the cornerstone of systemic anaphylaxis treatment. The rate of epinephrine absorption has not been reported previously in allergic children. Objective: Our objective was to study the clinical pharmacology of epinephrine in this population. Methods: We performed a prospective, randomized, blinded, parallel-group study in 17 children with a history of anaphylaxis to food, Hymenoptera venom, or other substances. We injected 0.01 ml/kg epinephrine solution (maximum 0.3 ml [0.3 mg]) subcutaneously, or 0.3 mg epinephrine intramuscularly from an autoinjector. Plasma epinephrine concentrations, heart rate, blood pressure, and adverse effects were monitored. Results: In nine children who received epinephrine subcutaneously, the mean maximum plasma epinephrine concentration (± SEM) was 1802 ± 214 pg/ml, achieved at a mean time of 34 ± 14 minutes (range, 5 to 120 minutes). Only two of the nine children achieved maximum plasma concentrations by 5 minutes. In eight children who received epinephrine intramuscularly, the mean maximum plasma concentration was 2136 ± 351 pg/ml, achieved at a mean time of 8 ± 2 minutes, which was significantly faster than the mean time at which maximum plasma concentrations were achieved after subcutaneous epinephrine injection ( p

A Comparison of Repeated High Doses and Repeated Standard Doses of Epinephrine for Cardiac Arrest Outside the Hospital

Abstract: Background Clinical trials have not shown a benefit of high doses of epinephrine in the management of cardiac arrest. We conducted a prospective, multicenter, randomized study comparing repeated high doses of epinephrine with repeated standard doses in cases of out-of-hospital cardiac arrest. Methods Adult patients who had cardiac arrest outside the hospital were enrolled if the cardiac rhythm continued to be ventricular fibrillation despite the administration of external electrical shocks, or if they had asystole or pulseless electrical activity at the time epinephrine was administered. We randomly assigned 3327 patients to receive up to 15 high doses (5 mg each) or standard doses (1 mg each) of epinephrine according to the current protocol for advanced cardiac life support. Results In the high-dose group, 40.4 percent of 1677 patients had a return of spontaneous circulation, as compared with 36.4 percent of 1650 patients in the standard-dose group (P=0.02); 26.5 percent of the patients in the high-dose ...

Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.

Abstract: Background The sympathetic nervous system has long been believed to be involved in the pathogenesis of panic disorder, but studies to date, most using peripheral venous catecholamine measurements, have yielded conflicting and equivocal results. We tested sympathetic nervous function in patients with panic disorder by using more sensitive methods. Methods Sympathetic nervous and adrenal medullary function was measured by using direct nerve recording (clinical microneurography) and whole-body and cardiac catecholamine kinetics in 13 patients with panic disorder as defined by the DSM-IV, and 14 healthy control subjects. Measurements were made at rest, during laboratory stress (forced mental arithmetic), and, for 4 patients, during panic attacks occurring spontaneously in the laboratory setting. Results Muscle sympathetic activity, arterial plasma concentration of norepinephrine, and the total and cardiac norepinephrine spillover rates to plasma were similar in patients and control subjects at rest, as was whole-body epinephrine secretion. Epinephrine spillover from the heart was elevated in patients with panic disorder ( P =.01). Responses to laboratory mental stress were almost identical in patient and control groups. During panic attacks, there were marked increases in epinephrine secretion and large increases in the sympathetic activity in muscle in 2 patients but smaller changes in the total norepinephrine spillover to plasma. Conclusions Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder. Epinephrine is released from the heart at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks. Contrary to popular belief, the sympathetic nervous system is not globally activated during panic attacks.

Effect of caffeine on metabolism, exercise endurance, and catecholamine responses after withdrawal

Abstract: In this study the effects of acute caffeine ingestion on exercise performance, hormonal (epinephrine, norepinephrine, insulin), and metabolic (free fatty acids, glycerol, glucose, lactate, expired ...

Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome.

Abstract: Background: Epinephrine is the drug of choice in advanced cardiac life support, but it can have deleterious side effects after restoration of spontaneous circulation. Objective: To investigate the ...

Effect of epinephrine on muscle glycogenolysis during exercise in trained men

Abstract: To test the hypothesis that an elevation in circulating epinephrine increases intramuscular glycogen utilization, six endurance-trained men performed two 40-min cycling trials at 71 +/- 2% of peak oxygen uptake in 20-22 degrees C conditions. On the first occasion, subjects were infused with saline throughout exercise (Con). One week later, after determination of plasma epinephrine levels in Con, subjects performed the second trial (Epi) with an epinephrine infusion, which resulted in a twofold higher (P < 0.01) plasma epinephrine concentration in Epi compared with Con. Although oxygen uptake was not different when the two trials were compared, respiratory exchange ratio was higher throughout exercise in Epi compared with Con (0.93 +/- 0.01 vs. 0.89 +/- 0.01; P < 0.05). Muscle glycogen concentration was not different when the trials were compared preexercise, but the postexercise value was lower (P < 0.01) in Epi compared with Con. Thus net muscle glycogen utilization was greater during exercise with epinephrine infusion (224 +/- 37 vs. 303 +/- 30 mmol/kg for Con and Epi, respectively; P < 0.01). In addition, both muscle and plasma lactate and plasma glucose concentrations were higher (P < 0.05) in Epi compared with Con. These data indicate that intramuscular glycogen utilization, glycolysis, and carbohydrate oxidation are augmented by elevated epinephrine during submaximal exercise in trained men.

Effect of epinephrine on lidocaine clearance in vivo: a microdialysis study in humans.

Abstract: BackgroundLocal anesthetic nerve block prolonged by epinephrine is thought to result from local vasoconstriction and consequent decreased local anesthetic clearance from the injection site. However, no study has yet confirmed this directly in humans by measuring tissue concentrations of local anesth

Postmenopausal hormone replacement: effects on autonomic, neuroendocrine, and immune reactivity to brief psychological stressors.

Abstract: Objective: Postmenopausal status increases some aspects of women's physiological responses to psychological stress; however, the influences of chronic hormone replacement with estrogen and progestogen on these responses are not known. We investigated possible effects of long-term estrogen replacement therapy (ERT). both with and without progestogen, on physiological reactivity to brief laboratory stressors. Method: We studied three groups of postmenopausal women: 16 on estrogen alone, 14 on estrogen and progestogen, and 25 control participants receiving no replacement therapy. Cardiovascular, neuroendocrine, and immune data were collected at baseline and after speech and math tasks. Results: In all groups, the stressors reduced vagal cardiac control (indexed by respiratory sinus arrhythmia); increased heart rate and plasma epinephrine, adrenocorticotropic hormone, and cortisol levels; and altered T lymphocyte response (measured by mitogen-induced cell proliferation), natural killer cell lysis, and circulating leukocyte subsets. Women on either type of ERT had higher total cortisol levels (reflecting an estrogen effect on cortisol binding globulin) and greater mitogen-induced blastogenesis across measurement periods than controls. They also showed greater vagal withdrawal and less decline in mitogen-stimulated blastogenesis in response to the stressors. Combined estrogen and progestogen was associated with higher epinephrine and lower circulating total lymphocytes, T cells, and CD4+ T cells across measurement periods, and with intermediate levels of vagal withdrawal in response to the stressors. Conclusions: Long-term ERT was associated with enhanced parasympathetic responsiveness to stress, suggesting possible reduced demand for potentially detrimental sympathetic activation; and with higher overall levels and smaller stress-induced reductions of mitogen-stimulated blastogenesis, suggesting

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients

Abstract: OBJECTIVE To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.

Physostigmine Prevents Postanesthetic Shivering As Does Meperidine or Clonidine

Abstract: BackgroundPostanesthetic shivering develops in as many as one half of patients recovering from isoflurane anesthesia. Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine. B

Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after [micro sign]-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification

Abstract: BACKGROUND: Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. METHODS: Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). RESULTS: Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P <0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. CONCLUSIONS: Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists

Adrenal medulla and exercise training.

Abstract: The adrenaline release from the adrenal medulla increases during exercise, but at a given absolute work intensity the magnitude of this response is less pronounced in endurance trained vs sedentary individuals most likely due to a lower sympathetic stimulation of the adrenal medulla. However, when trained and untrained subjects are compared at identical relative work loads as well as in response to numerous non-exercise stimuli. endurance trained athletes have a higher epinephrine secretion capacity compared to sedentary individuals. This indicates a development of a so-called "sports adrenal medulla" as a result of a long term adaptation of an endocrine gland to physical training. Such an adaptation is parallel to adaptations taking place in other tissues like skeletal muscle and the heart. and can be advantageous in relation to both exercise performance in the competing athlete and cause a biological rejuvenation in relation to aging.

Plasma catecholamines and haemodynamic changes during pneumoperitoneum

Abstract: Background: Insufflation of CO2 into the abdomen is used during all kinds of laparoscopic operations. The procedure elicits haemodynamic and hormonal responses. The reports on sympathetic responses to laparoscopic surgery have been conflicting. However, few studies have assessed sympathetic and haemodynamic responses to CO2 insufflation per se, eliminating possible effects of intubation, skin incision, surgical manipulation and positioning of the body. No studies have measured both venous and arterial plasma catecholamines, the latter being a more sensitive indicator of sympathetic activity. In the present study, we hypothesised an increased sympathetic activity during pneumoperitoneum and an association between haemodynamic and sympathetic responses. Methods: Plasma adrenaline and noradrenaline from the radial artery and superior vena cava were measured immediately before and 10 min after abdominal insufflation of CO2 in 11 subjects. Haemodynamics were monitored invasively. Results: During pneumoperitoneum arterial plasma noradrenaline increased from 155 (106, 209) pg/ml (median, lowest and highest quartile) to 283 (188, 378) pg/ml (P=0.003), while there were no changes in arterial plasma adrenaline. The calculated arterial-superior vena cava difference in plasma noradrenaline did not change, indicating no increased sympathetic activity in the drainage area of the superior vena cava. Heart rate and cardiac index were unchanged, while total peripheral resistance and mean arterial blood pressure increased (P=0.002). The changes in arterial plasma noradrenaline were closely related to the changes in total peripheral resistance (r=0.69, P=0.01). Conclusions: Plasma noradrenaline increases during pneumoperitoneum and is associated with changes in total peripheral resistance. Plasma adrenaline is unchanged and there is no evidence of increased sympathetic outflow to the drainage area of the superior vena cava. Thus, the increase in plasma noradrenaline may be due to more local activation of the sympathetic nervous system, probably somewhere from the drainage area of the inferior vena cava.

Vasopressin Combined With Epinephrine Decreases Cerebral Perfusion Compared With Vasopressin Alone During Cardiopulmonary Resuscitation in Pigs

Abstract: Background and Purpose—It is unknown whether a combination of vasopressin and epinephrine may be superior to vasopressin alone by targeting both nonadrenergic and adrenergic receptors. Methods—After 15 minutes of cardiac arrest (13 minutes of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3 minutes of chest compressions, 16 animals were randomly treated with either 0.8 U/kg vasopressin (n=8) or 0.8 U/kg vasopressin combined with 200 μg/kg epinephrine (n=8). Results—Comparison of vasopressin with vasopressin and epinephrine at 90 seconds and 5 minutes after drug administration resulted in comparable mean (±SEM) coronary perfusion pressure (54±3 versus 57±5 and 36±4 versus 35±4 mm Hg, respectively), cerebral perfusion pressure (59±6 versus 65±8 and 40±6 versus 39±6 mm Hg, respectively), and median (25th to 75th percentiles) left ventricular myocardial blood flow [116 (81 to 143) versus 108 (97 to 125) and 44 (35 to 81) versus 62 (42 to 74) mL · min−1 · 100 g−1, respectively], b...

Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle

Abstract: We examined the effects of epinephrine (25, 50, and 150 nM) on 1) basal and insulin-stimulated 3-O-methylglucose (3-MG) transport in perfused rat muscles and2) GLUT-4 in skeletal muscle plasma memb...

Therapeutic controversies in the management of acute anaphylaxis.

Abstract: At present there are few controlled clinical therapeutic trials in acute anaphylaxis despite the emergence of evidence based medicine. Moreover, the explosive nature, unpredictable onset, and usually rapid response to treatment that characterise acute anaphylaxis mean that this situation is unlikely to change.' The vast majority of serious anaphylactic reactions occur unexpectedly,2 typically in fit patients. Anaphylaxis is rarely seen or described in critically ill or shocked patients other than in those with asthma.1 Therefore, treatment recommendations have to be based on clinical observation, interpretation of the pathophysiology and, to an extent, animal studies.' However, descriptions of the management of anaphylaxis, for instance those in Hospital Update in 19914 and on angio-oedema in the British Medical Journal in 1992,5 are often then criticised for the treatment recommended.9 A recent expert opinion by Fisher on the treatment of acute anaphylaxis\" was followed by no less than 10 letters in response, many of which contained errors of logic as pointed out by Fisher in replying to them.\" Clearly there is confusion about the correct management of acute anaphylaxis. Much of the controversy is due to misinterpretation of published reports. In this review I reassess the role, route of delivery, dose, concentration, and efficacy of the various drugs used in anaphylaxis. Adrenaline, steroids, antihistamines, fluids, glucagon, aminophylline, and discharge drugs will be discussed in detail. I shall use the term \"anaphylaxis\" to refer to both anaphylactic reactions (IgE mediated immediate type hypersensitivity reactions) and anaphylactoid reactions (non-immunologically triggered), as the clinical expression and final mediators involved are identical.'2 Tables are included giving clear recommendations for first line, second line, and discharge treatment, and allowing rapid evaluation of the drugs involved. Adrenaline

Central nervous system nitric oxide synthase activity regulates insulin secretion and insulin action.

Abstract: Systemic inhibition of nitric oxide synthase (NOS) with NG-monomethyl-L-arginine (L-NMMA) causes acute insulin resistance (IR), but the mechanism is unknown. We tested whether L-NMMA-induced IR occurs via NOS blockade in the central nervous system (CNS). Six groups of Sprague-Dawley rats were studied after chronic implantation of an intracerebroventricular (ICV) catheter into the lateral ventricle and catheters into the carotid artery and jugular vein. Animals were studied after overnight food deprivation, awake, unrestrained, and unstressed; all ICV infusion of L-NMMA or D-NMMA (control) were performed with artificial cerebrospinal fluid. ICV administration of L-NMMA resulted in a 30% rise in the basal glucose level after 2 h, while ICV D-NMMA had no effect on glucose levels. Insulin, epinephrine, and norepinephrine levels were unchanged from baseline in both groups. Tracer (3H-3-glucose)-determined glucose disposal rates during 2 h euglycemic hyperinsulinemic (300 microU/ml) clamps performed after ICV administration of L-NMMA were reduced by 22% compared with D-NMMA. Insulin secretory responses to a hyperglycemic clamp and to a superimposed arginine bolus were reduced by 28% in L-NMMA-infused rats compared with D-NMMA. In conclusion, ICV administration of L-NMMA causes hyperglycemia via the induction of defects in insulin secretion and insulin action, thus recapitulating abnormalities observed in type 2 diabetes. The data suggest the novel concept that central NOS-dependent pathways may control peripheral insulin action and secretion. This control is not likely to be mediated via adrenergic mechanisms and could occur via nonadrenergic, noncholinergic nitrergic neural and/or endocrine pathways. These data support previously published data suggesting that CNS mechanisms may be involved in the pathogenesis of some forms of insulin resistance and type 2 diabetes independent of adiposity.

Adrenal epinephrine increases alveolar liquid clearance in a canine model of neurogenic pulmonary edema.

Abstract: Case reports of neurogenic pulmonary edema (NPE) often indicate that the edema resolves quickly. Because plasma epinephrine concentration may be elevated in NPE, and epinephrine has been shown to increase the rate of alveolar liquid clearance (ALC), we determined if ALC was increased in a canine model of NPE produced by the intracisternal administration of veratrine. ALC was determined by instilling autologous plasma into a lower lung lobe and using the increase in instillate protein concentration after 4 h to calculate the volume of fluid cleared from the airspaces by mass balance. To prevent pulmonary hypertension and edema, which would confound the mass balance analysis, carotid arterial blood was allowed to drain into a reservoir as pulmonary arterial pressure started to rise after veratrine administration. ALC in animals administered veratrine (n = 6) was 30.4 +/- 1.6 (SE)% of the instilled volume compared with 14.1 +/- 2.1% observed in control animals. The increase in ALC could be inhibited by adrenalectomy, beta2-adrenergic blockade using ICI 118,551, or sodium channel blockade using amiloride and could be duplicated by infusing epinephrine to increase plasma epinephrine concentration to levels observed in NPE. These data indicate that the increased ALC was mediated by adrenal epinephrine and suggest that edema resolution in patients with NPE might be accelerated by endogenous epinephrine.

Direct effects of stress on adrenocortical function.

Abstract: The adrenal gland plays a pivotal role in the stress response since this response involves the hypothalamic-pituitary-adrenal axis (HPAA) and the sympatho-adrenomedullary system (SAMS) as its two principal components. An important relation between the immune system and the other stress response systems is also centered on the adrenal gland. It is well known that the cortex secretes glucocorticoids while the medulla secretes epinephrine, two of the major effects of the stress response. Some other aspects, however, also deserve special consideration: The paracrine effects of the cortical secretion on the medullary cells through the special irrigation system of the gland and reciprocally the influence of the medulla upon the cortex, either by direct close contact or by local innervation. The influence of vascular events also needs to be considered as well as the existence of some local hormonal axis such as those resulting from the local production of renin or CRH in adrenal cells. Some other cells such as mast cells, macrophages and endothelial cells seem to play a role in the regulation of the adrenal cortex and hence in the tuning of the stress response. Stressors stimulate the release of CRH from the hypothalamic paraventricular nucleus inducing the secretion of ACTH from the pituitary and that of corticosteroids from the adrenal cortex. Through the activation of the sympathetic system the adrenal can be stimulated even before adequate levels of ACTH are reached. In conditions of chronic stress the adrenal cortex undergoes an adaptation that allows the hypersecretion of glucocorticoids to occur even without the increment of ACTH.

Effects of epinephrine on lipid metabolism in resting skeletal muscle

Abstract: The effects of physiological (0, 0.1, 2.5, and 10 nM) and pharmacological (200 nM) epinephrine concentrations on resting skeletal muscle lipid metabolism were investigated with the use of incubated rat epitrochlearis (EPT), flexor digitorum brevis (FDB), and soleus (SOL) muscles. Muscles were chosen to reflect a range of oxidative capacities: SOL > EPT > FDB. The muscles were pulsed with [1-14C]palmitate and chased with [9,10-3H]palmitate. Incorporation and loss of the labeled palmitate from the triacylglycerol pool (as well as mono- and diacylglycerol, phospholipid, and fatty acid pools) permitted the simultaneous estimation of lipid hydrolysis and synthesis. Endogenous and exogenous fat oxidation was quantified by 14CO2 and 3H2O production, respectively. Triacylglycerol breakdown was elevated above control at all epinephrine concentrations in the oxidative SOL muscle, at 2.5 and 200 nM (at 10 nM, P = 0.066) in the FDB, and only at 200 nM epinephrine in the EPT. Epinephrine stimulated glycogen breakdown in the EPT at all concentrations but only at 10 and 200 nM in the FDB and had no effect in the SOL. We further characterized muscle lipid hydrolysis potential and measured total hormone-sensitive lipase content by Western blotting (SOL > FDB > EPT). This study demonstrated that physiological levels of epinephrine cause measurable increases in triacylglycerol hydrolysis at rest in oxidative but not in glycolytic muscle, with no change in the rate of lipid synthesis or oxidation. Furthermore, epinephrine caused differential stimulation of carbohydrate and fat metabolism in glycolytic vs. oxidative muscle. Epinephrine preferentially stimulated glycogen breakdown over triacylglycerol hydrolysis in the glycolytic EPT muscle. Conversely, in the oxidative SOL muscle, epinephrine caused an increase in endogenous lipid hydrolysis over glycogen breakdown.

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

Abstract: OBJECTIVE: To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA: Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS: ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS: All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS: Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.

Reduced GABA inhibition of sympathetic function in renal-wrapped hypertensive rats

Abstract: Animals with bilateral cannulas in the paraventricular nucleus were made hypertensive by a one-kidney, figure eight renal wrap procedure or sham operated. Femoral artery and vein catheters were inserted for arterial pressure measurement and plasma catecholamine determination. After recovery and 4 days after hypertension surgery, bicuculline methiodide or muscimol was microinjected into the paraventricular nucleus. In some rats, nitroprusside was infused intravenously to reflexly stimulate the sympathetic nervous system. In control rats, bicuculline increased blood pressure, heart rate, and plasma norepinephrine and epinephrine concentrations. In contrast, in hypertensive rats blood pressure did not change while the heart rate response was maintained. Plasma norepinephrine and epinephrine responses were reduced 75 and 68%, respectively. Muscimol injections decreased arterial pressure in the hypertensive rats. Heart rate responses to nitroprusside were similar in the two groups of rats, while the plasma catecholamine responses were attenuated in the hypertensive animals. These data suggest that GABA function in the paraventricular nucleus is reduced in renal wrap hypertension.

Isoflurane and Sevoflurane Augment Norepinephrine Responses to Surgical Noxious Stimulation in Humans

Abstract: Background Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics. Methods Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. Results Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase and area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. Conclusion The effects of isoflurane and sevoflurane on the surgical noxious stimulation-induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation-induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.

Effects of epinephrine on glucose metabolism in contracting rat skeletal muscles

Abstract: The effects of epinephrine on glucose metabolism during contractile activity and insulin stimulation were investigated in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles from Wistar r...

Anxiety and pain: epinephrine-induced hyperalgesia and attentional influences

Abstract: The role of peripheral epinephrine in the influence of anxiety on pain was investigated by intravenously infusing epinephrine and placebo in three increasing doses. The effect of epinephrine was measured within subjects on several subjective and autonomic measures: subjective pain, skin conductance response, heart rate response due to electrical stimulation, threshold for heat pain and threshold for pressure pain. Heat pain threshold was measured both on normal skin and on skin sensitized with capsaicin, since there is evidence that effects of sympathetic stimulation are only to be found in damaged or sensitized skin. Epinephrine caused a slight increase in subjective pain due to electrical stimulation and a decrease in heat pain threshold, which was larger on capsaicin-treated than on normal skin. However, heart rate response due to electrical stimulation and pressure pain threshold were not significantly influenced, while skin conductance response was even inhibited by epinephrine. Attentional focus, which was manipulated within electrical stimulation, seemed to have a much stronger influence on pain responses than pharmacological manipulation, independent of epinephrine. It may be speculated that, although evidence was found for effects of epinephrine on pain, they may be overruled by effects of attention.

Epinephrine in digital blocks: revisited.

Abstract: Digital block anesthesia with epinephrine, ring technique, and digital tourniquet have been implicated in causing finger gangrene. An extensive review of the literature provided no case of finger gangrene attributed solely to the adjunctive use of epinephrine with lidocaine for digital block. By causing vasoconstriction, epinephrine complements the local analgesic by prolonging the duration of action and providing a temporary hemostatic effect. Epinephrine augmentation of digital block anesthesia was used in the treatment of 23 finger injuries without a complication.