Showing papers on "Epinephrine published in 1989"

Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats.

Abstract: The effects of three potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles on sympathoadrenomedullary and hypothalamo-pituitary-adrenocortical axis functions were assessed in conscious, freely moving male Sprague-Dawley rats. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI), all produced marked dose-dependent increases in plasma epinephrine and ACTH concentrations. Both epinephrine and ACTH responses peaked at 10 min and showed strong positive correlations across all drugs and doses studied. Corticosterone increases showed a saturable response pattern and were close to the maximum level with a relatively small (approximately 2.5-fold) increase in plasma ACTH concentrations. Norepinephrine levels showed small dose-dependent increases after 8-OH-DPAT and m-CPP and decreases after DOI treatment. These results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis can be activated via 5-HT1 and 5-HT2 receptors and that these two systems may have common or similar regulatory mechanisms triggered by these stimuli.

In the Rat, Interleukin- lα and -β Stimulate Adrenocorticotropin and Catecholamine Release*

Abstract: Recombinant interleukin-1 alpha and -beta (Il-1 alpha and -beta) have been evaluated for their abilities to stimulate ACTH and catecholamine secretion in the intact adult male rat. Additionally, the role of adrenergic-dependent pathways in mediating Il-1-induced ACTH release has been assessed. The iv or intracerebroventricular injection of either Il-1 alpha or Il-1 beta caused dose-related increases in plasma ACTH, epinephrine, and norepinephrine levels. While at low iv doses (less than or equal to 10 ng), Il-1 beta was more effective than Il-1 alpha at releasing ACTH, no measurable differences were noted at higher doses. In contrast, Il-1 beta was significantly more active at all doses in elevating plasma ACTH levels after intracerebroventricular injection. Similarly, Il-1 alpha was more effective than Il-1 beta at stimulating epinephrine, but not norepinephrine, secretion after icv injection. Because of the ability of catecholamines to alter ACTH secretion, we then examined the role of adrenergic-dependent pathways as possible mediators of Il-1-induced ACTH secretion. Blockade of adrenergic receptors by the concomitant administration of prazosin and propanolol prevented the simultaneous actions of phenylephrine and isoproterenol on the corticotrophs, but did not significantly alter the effect of peripherally administered Il-1 alpha on ACTH release. These results suggest that both Il-1 alpha and Il-1 beta stimulate ACTH and catecholamine secretion in the rat. Despite the ability of the lymphokine to elevate plasma epinephrine and norepinephrine values, circulating catecholamines do not appear to represent essential modulators of ACTH release induced by acutely injected Il-1.

Neuroendocrine, sympathetic and metabolic responses induced by interleukin-1.

Abstract: Effects on turnover of vasopressin (AVP) in the hypothalamus and on secretion of pituitary hormones, catecholamines and insulin after intraperitoneal injection of recombinant interleukin-1 (beta) (IL-1) were investigated in male wistar rats. Intraper-itoneal administration of IL-1 in a dose (1 µg) that maximally activated pituitary-adrenal activity failed to alter plasma concentrations of prolactin, luteinizing hormone and melanocyte-stimulating hormone. Rats chronically cannulated in the right jugular veins showed a time-related increase in plasma corticosterone concentrations in response to intraperitoneal administration of IL-1 that lasted up to 4 h. In the same rats, plasma epinephrine (E) and norepinephrine (NE) concentrations were only slightly elevated (2-fold increase) at 30 min and at 1 h after IL-1 administration. Unlike in endotoxin-resistant C3H/HeJ mice, where IL-1 induces hypoglycemia, IL-1 did not affect plasma concentrations of glucose and insulin in Wistar rats. In the zona externa of the median eminence, IL-1 stimulated corticotropin-releasing factor (CRF) turnover at an approximate rate of 15%/h, but did not cause a concomitant change in AVP turnover as can be observed after insulin-induced hypoglycemia. Since half of the hypothalamic CRF neurons have been shown to costore AVP, the data favor the view of a selective effect of IL-1 on a subtype of CRF neurons. We conclude that pituitary-adrenal activation in response to II-1 is caused by CRF secretion from a subtype of CRF neurons (not storing AVP) in the rat hypothalamus. Furthermore, the small and transient increase of plasma E and NE may be caused by a presynaptic action of IL-1 on sympathetic nerves in immune and/or other organs or may involve central CRF projections regulating sympathetic outflow.

Effects of local anesthesia on nerve blood flow: studies using lidocaine with and without epinephrine

Abstract: Peripheral nerves have a dual blood supply of intrinsic exchange vessels in the endoneurium and an extrinsic plexus of supply vessels in the epineurial space that cross the perineurium to anastomose with the intrinsic circulation. The extrinsic supply is responsive to adrenergic stimuli. In this study we measured nerve blood flow in rat sciatic nerves with a laser Doppler flow probe. Normal saline, solutions of 1% or 2% lidocaine HCl with and without 1:200,000 epinephrine, or 1:200,000 epinephrine in normal saline were topically applied to the nerves to determine their effect on nerve blood flow. At the end of the subsequent 10-min recording period, blood flow was significantly depressed for all of the solutions tested except saline. Reductions of blood flow ranged from 19.3% for 1% lidocaine HCl to 77.8% for 2% lidocaine HCl with epinephrine. Epinephrine by itself significantly reduced nerve blood flow; when added to local anesthetic solutions, it reduced nerve blood flow to a greater extent than the reduction caused by anesthetics alone. There was an additional significant reduction in nerve blood flow when the epinephrine groups were compared with the pure local anesthetic groups.

Muscle sympathetic activity and norepinephrine release during mental challenge in humans

Abstract: Muscle sympathetic nerve activity (MSA; peroneal nerve) and arterial and femoral venous plasma norepinephrine (NE) were studied in 10 volunteers at rest, during a relaxation procedure (RELAX), and ...

Epidural Morphine Decreases Postoperative Hypertension by Attenuating Sympathetic Nervous System Hyperactivity

Abstract: Twenty-four adults who were undergoing operations on the abdominal aorta were enrolled in a randomized, double-blind, placebo-controlled study in which epidural morphine sulfate (6 mg) was employed to attenuate the sympathoadrenal response to surgery to evaluate the possible contribution of sympathetic nervous system hyperactivity to postoperative hypertension. Patients who received epidural morphine required less parenteral morphine in the 24 hours following surgery, had lower analogue pain scores, and had markedly lower plasma norepinephrine levels when compared with patients in the control group who received an identical volume of saline in the epidural space. Epidural morphine had no effect on plasma epinephrine or arginine vasopressin levels. Fewer patients in the morphine group (4 of 12 vs 9 of 12 patients in the saline group) required treatment for hypertension (mean arterial blood pressure, ≥110 mm Hg) in the 24 hours following surgery. In addition, patients in the morphine group had lower blood pressures in the 24 hours following surgery. These data suggest that sympathetic nervous system activity and not adrenal epinephrine or pituitary secretion of arginine vasopressin is responsible for the development of hypertension following aortic surgery. Furthermore, epidural narcotics appear to provide a means of attenuating this response. (JAMA. 1989;261:3577-3581)

Neutralized Lidocaine with Epinephrine for Local Anesthesia

Abstract: . The pain of infiltrating lidocaine with epinephrine into skin is reduced by the addition of sodium bicarbonate. The effect of varied concentrations of sodium bicarbonate on pain of infiltration of 1% lidocaine with epinephrine 1:100,000 was measured. Sodium bicarbonate at 40 and 100 meq/L of anesthetic solution caused significantly less pain than did 0 or 10 meq/L. The stability of epinephrine in a solution at pH 7.3 was also determined. Epinephrine concentration declined approximately 25% per week in anesthetic solution containing 100 meq/L sodium bicarbonate.

Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin.

Abstract: An increase in cardiac beta-adrenergic sensitivity or beta-receptor density or both has been described in several animal species after denervating the heart. The transplanted human heart is also denervated and, therefore, may exhibit supersensitivity to beta-adrenergic agonists and an increase in beta-adrenergic receptor density. In 16 patients examined 1-3 months after orthotopic cardiac transplantation, beta-adrenergic receptor density measured by [125I]iodocyanopindolol binding in endomyocardial biopsy specimens was not significantly different in transplant recipients compared with normal controls (transplant = 1,429 +/- 199, control = 1,728 +/- 263 fmol/g wet wt; p = NS). However, when normalized to Lowry protein, the [125I]iodocyanopindolol in beta-adrenergic receptor density in biopsy tissue from transplant recipients was significantly lower than in tissue from controls (transplant = 58.1 +/- 6.2, control = 93.5 +/- 13.4 fmol/g Lowry protein; p = 0.011). Atrial sinus node activity of the denervated donor heart and the innervated atrial cuff of the native recipient heart could be detected on the surface electrocardiogram in six patients. In these six patients, the heart rate response to graded infusions of epinephrine (taken up by the adrenergic nerve terminals) and isoproterenol (not taken up by the adrenergic nerve terminals) was measured. The epinephrine dose-response curve in transplanted donor atria was significantly to the left of the native recipient atrial dose-response curve (p less than 0.0001). The isoproterenol dose-response curves for native and transplanted atria were not different. We conclude that myocardial beta-adrenergic receptors are not increased in human orthotopic cardiac allografts and that there is no evidence for beta-receptor-mediated supersensitivity of postsynaptic origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle

Abstract: The thermic effect of carbohydrate has a component mediated by the sympathoadrenal system but of unknown anatomical localization. We have studied the contribution of skeletal muscle to the thermic effect of a carbohydrate-rich natural meal (115 g of carbohydrate, approximately 80% of energy) by means of the forearm technique on two occasions, with and without intravenous beta-blockade with propranolol. The meal-induced thermogenesis was reduced from 9.6 to 7.1% by beta-blockade (P less than 0.04), the major difference was found 90 to 240 min after the meal. The postprandial increments in plasma glucose and lactate did not change by beta-blockade, but there was a trend toward a decreased insulin response (P = 0.06). The carbohydrate-induced increase in forearm oxygen consumption was reduced by 23% after beta-blockade (P less than 0.05), the entire difference being present 90-180 min postprandially and coinciding with the peak in arterial epinephrine. The present study provides evidence of a facultative thermogenic component in skeletal muscle, mediated by epinephrine via beta 2-adrenoreceptors. However, it also points to a nonmuscle component mediated through beta 1-adrenoceptors by norepinephrine released from the sympathetic nervous system. Consequently, the sympathoadrenal system seems to play a physiological role in the daily energy balance.

Adrenal and sympathetic catecholamines in exercising rats

Abstract: The effects of adrenodemedullation and/or adrenoceptor agonists and antagonists on plasma epinephrine (E) and norepinephrine (NE) concentrations during exercise were investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. E was not detectable in plasma of adrenodemedullated (Adm) rats. A marked reduction in the normal exercise-induced increase in plasma NE concentrations occurred in both Adm rats as well as in intact rats injected with the beta 2-selective adrenoceptor antagonist ICI 118551. Intravenous infusion of either E or the beta 2-selective agonist fenoterol restored the increase in plasma NE in Adm rats. Injection of the alpha 2-selective antagonist yohimbine in combination with infusion of the beta 2-selective agonist fenoterol into Adm rats caused an enormous increase in plasma NE. It is concluded that all NE in plasma as released during exercise originates from the peripheral nerve endings of the sympathetic nervous system. Adrenal E influences the release of NE via activation of presynaptic beta 2-adrenoceptors.

Characterization of endothelin-1 stimulation of catecholamine release from adrenal chromaffin cells.

Abstract: Addition of endothelin-1 (ET-1) to primary cultures of bovine adrenal chromaffin cells causes a significant enhancement of norepinephrine and epinephrine efflux, with an EC50 of about 1 nM. A maximally effective concentration of endothelin (10 nM) gives a transient increase in noradrenaline release within 5 min. The amounts of noradrenaline and adrenaline released by ET-1 was smaller than the release elicited by maximally effective concentrations of bradykinin or prostaglandin E2. These results raise the possibility that the vascular endothelium may stimulate release from chromaffin cells by production of ET-1.

Single-Dose Ethanol Administration Activates the Hypothalamic-Pituitary-Adrenal Axis: Exploration of the Mechanism of Action

Abstract: Activation of the hypothalamic-pituitary-adrenal axis (HPAA) by single-dose ethanol administration, which achieved moderately high blood ethanol levels, was explored in naive rats in order to determine the mechanism of ethanoΓs activation of the stress axis. Adult male rats received a single dose (3.2 g/kg body weight–1 of a 12% solution of ethanol in physiological saline. The plasma concentration of immunoreactive (ir) adrenocorticotropic hormone (ACTH), beta-endorphin (BE) and corticosterone (CS) was determined by radioimmunoassay, whereas, plasma concentrations of epinephrine (E) and norepinephrine (NE) were quantified following reverse-phase liquid chromatographic separation and amperometric detection. Ethanol induced maximal plasma ACTH levels within minutes, which declined toward basal levels by 60 min, whereas, plasma concentration of CS rose rapidly and remained elevated at 60 min. Plasma ACTH and CS levels in saline-treated control animals did not vary significantly at any time point. Consistent with co-release of ACTH from corticotrophs, the plasma concentration of ir-BE increased 5-fold at 15 min and declined towards basal levels at 60 min after-ethanol challenge. Plasma E increased 10- to 20-fold as compared to saline controls or preinjection levels and returned to preinjection levels by 90 min, in a manner similar to ethanol-induced changes in proopiomela-nocortin-derived peptides and CS. Removal of the adrenal medulla and thus the source of E prior to ethanol administration, did not attenuate activation of the HPAA. Passive immunoneutralization of arginine vasopressin (AVP), using a high-titer AVP anti-serum and a protocol which was found to block ether-induced ACTH secretion by 40% in adult male rats, failed to even partially block ethanol-induced ACTH or CS secretion. The results of this study indicate that neither adrenal medulla-derived E nor AVP are significant regulators or coregulators of corticotroph secretions following a moderately high, single-dose, intragastric administration of ethanol.

Effects of vasopressin and catecholamines on the maintenance of circulatory stability in brain-dead patients.

Abstract: The effectiveness and reliability of long-term control of circulatory stability in brain-dead patients by combined administration of vasopressin and catecholamine was examined in detail. Twenty-five patients were divided into three groups according to the dose of vasopressin. The first group (n = 10) received no vasopressin, the second group (n = 2) an antidiuretic dose (0.1-0.4 U/hr), and the third group (n = 13) a pressor dose (1-2 U/hr), respectively. Patients given no vasopressin or an antidiuretic dose demonstrated circulatory deterioration and cardiac arrest within a short time after brain death, despite administration of a large dose of epinephrine. All patients with a pressor dose of vasopressin, however, demonstrated stable circulation as long as vasopressin and epinephrine were administered. Five patients in whom stable circulation was maintained by this technique were randomly chosen from the third group and studied under the following four conditions: (1) neither vasopressin nor epinephrine; (2) vasopressin only; (3) epinephrine only; and (4) both vasopressin and epinephrine. Compared with the controls (neither vasopressin nor epinephrine), vasopressin only increased the total peripheral resistance index, whereas epinephrine alone increased the cardiac index. Combined administration, however, raised the mean arterial blood pressure significantly by markedly increasing the total peripheral resistance index and cardiac index. Finally, in four brain-dead patients also randomly chosen from the third group, epinephrine, norepinephrine, and dopamine were compared in their circulatory effects with a pressor dose of vasopressin. Epinephrine increased both the total peripheral resistance index and cardiac index, whereas norepinephrine increased the total peripheral resistance index, compared with the baseline (no catecholamine). The required dose of norepinephrine, however, was four times that of epinephrine. The major effect of dopamine was to increase the cardiac index. We conclude that a pressor dose of vasopressin plays a central role in circulatory stabilization of brain-dead patients, and that long-term maintenance of stable circulation for a desired length of time is possible by the combined use of vasopressin and a catecholamine. Individually, catecholamines exhibit characteristic differences. Epinephrine has significant effects on both peripheral vessels and the heart, whereas norepinephrine keeps the circulation stable by increasing the total peripheral resistance index, with a much larger dose than epinephrine. Dopamine acts primarily on the heart.

Increased fat and skeletal muscle beta-adrenergic receptors but unaltered metabolic and hemodynamic sensitivity to epinephrine in vivo in experimental human thyrotoxicosis.

Abstract: Based largely on evidence of increased target tissue beta-adrenergic receptor densities and responsiveness in animal and, to a lesser extent, human tissues, it is often assumed that thyroid hormone excess results in increased sensitivity to catecholamines in vivo, thus explaining several clinical manifestations of thyrotoxicosis. To test the hypothesis that thyrotoxicosis results in increased target tissue beta-adrenergic receptor densities and correspondingly increased metabolic and hemodynamic sensitivity to epinephrine in vivo, we measured these in 10 normal humans before and after administration of triiodothyronine (100 micrograms daily) for 10 d. Thyrotoxicosis increased beta-adrenergic receptor densities in fat (approximately 60%) and skeletal muscle (approximately 30%). Despite increments in beta-adrenergic receptor densities in these and probably other target tissues, metabolic and hemodynamic sensitivity to epinephrine in vivo was unaltered. An apparently adaptive increase in insulin secretion plausibly explains normal glycemic, glycogenolytic/glycolytic, lipolytic, and ketogenic sensitivity to epinephrine in the thyrotoxic state. In view of this striking homeostatic efficiency of the intact individual, the finding of altered adrenergic receptors, even in relevant target tissues, should not be extrapolated to altered sensitivity to catecholamines in vivo in the absence of direct testing of that hypothesis. With respect to the clinical issue, these data suggest that increased sensitivity to catecholamines does not explain clinical manifestations of thyrotoxicosis in humans.

Effect of antiasthma drugs on microvascular leakage in guinea pig airways

Abstract: We have studied the effect of intravenous epinephrine, albuterol, verapamil, and aminophylline on airway microvascular leakage in guinea pigs. Microvascular leakage was induced by platelet-activating factor (PAF; 50 ng/kg intravenously), which acts directly on venular endothelial cells, and measured by quantifying extravasation of Evans blue (EB) dye. Epinephrine (20 micrograms/kg) inhibited PAF-induced changes in dye leakage in larynx and main bronchi; at 80 and 160 micrograms/kg, significant inhibition was observed in all airways studied. This effect was reversed by phentolamine (2.5 mg/kg) or prazosin (100 micrograms/kg). By contrast, albuterol (20 to 320 micrograms/kg) and aminophylline (12.5 to 50 mg/kg) failed to inhibit dye leakage at any dose studied. Verapamil inhibited PAF-increased leakage in larynx, main bronchi, and intrapulmonary airways at the lowest dose tested (125 micrograms/kg), although inhibition was not dose dependent. These results suggest that the antiedema effect of epinephrine may be due to vasoconstriction rather than to a direct effect on endothelial cell contractility and that neither beta-agonists nor theophylline have an inhibitory effect. The inhibitory effect of epinephrine on airway microvascular leakage may have therapeutic implications for asthma.

Posttraumatic skeletal muscle proteolysis: the role of the hormonal environment.

Abstract: To investigate the role of hormones as mediators of net skeletal muscle proteolysis following injury, healthy normal male volunteers received a continuous 76-hour infusion of the 3 “stress“ hormones: hydrocortisone, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Ten paired studies were conducted. Diets were constant and matched on both occasions. Triple hormone infusion achieved hormone concentrations similar to those seen following mild-moderate injury. After 72 hours of infusion, skeletal muscle intracellular glutamine concentrations were lower in the hormone studies than in the control group (N=4). Free amino acid concentrations in arterial whole blood and forearm amino acid efflux were little affected by hormonal infusion. Thus, alteration of the hormonal environment by the triple hormone infusion was not a sufficient stimulus to induce all of the changes in skeletal muscle proteolysis observed in critical illness. Since studies utilizing neurohormonal blockade have shown diminished net muscle proteolysis, the stress hormones appear to be necessary but not sufficient for the protein catabolic response to injury.

Long-term cortisol treatment impairs behavioral and neuroendocrine responses to 5-HT1 agonists in the rat.

Abstract: The effects of chronic cortisol treatment on neuroendocrine and behavioral responses to serotonim (5-HT1) receptor agonists were studied in conscious, freely moving rats. Seven-day cortisol treatment (25 mg/kg/day with osmotic minipumps) markedly suppressed basal plasma corticotropin (ACTH) and corticosterone concentrations, indicating a suppression of the hypothalamo-pituitary-adrenocortical axis. Cortisol also decreased body weight, food intake, plasma norepinephrine (NE), and epinephrine (E) levels. In the drug challenge studies, we used two 5-HTι agonists, the 5-HT1B and 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), to examine the effect of cortisol on their behavioral and neuroendocrine effects. After 7-day cortisol treatment, plasma prolactin responses to both m-CPP and 8-OHDPAT were significantly decreased. While the plasma NE, E, and food intake responses to m-CPP were also significantly reduced by cortisol treatment, these same responses to 8-OHDPATwere unchanged. The effect of m-CPP on locomotor activity was also decreased. Since only the responses to m-CPP and 8-OHDPAT previously shown to be antagonized by pretreatment with the 5-HT1/5-HT2 antagonist, metergoline, were significantly attenuated after cortisol treatment, these changes may be specific to 5-FΓT receptors. These data indicate that chronic exposure to high glucocorticoid levels alters 5-HT1 receptor-mediated functions and provides additional evidence relevant to the contribution of glucocorticoid elevation to the symptoms of depression.

Insulin, glucagon, and catecholamines in prevention of hypoglycemia during fasting

Abstract: To dissect the mechanisms of the prevention of hypoglycemia during fasting, eight normal humans were studied after overnight and 3-day fasts. Prolonged fasting resulted in the expected decrements in base-line glucose production and plasma glucose, insulin, and C-peptide and increments in plasma glucagon, epinephrine, norepinephrine, growth hormone, and cortisol. After the overnight and 3-day fasts, insulin restoration (0.2 mU.kg-1.min-1) alone resulted in transient decrements in glucose production and only 15 and 19% decrements in plasma glucose, respectively. Selective glucagon deficiency (somatostatin infusion with insulin and growth hormone replacement) resulted in transient decrements in glucose production and additional 24 and 29% decrements in plasma glucose, respectively. Notably, plasma glucose plateaued under both fasting conditions in both instances. Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusions) alone had no effect on glycemia under either fasting condition. However, progressive hypoglycemia developed during adrenergic blockade coupled with glucagon deficiency after the overnight fast (85 +/- 2 to 48 +/- 4 mg/dl, P less than 0.001) and after the 3-day fast (65 +/- 2 to 33 +/- 1 mg/dl, P less than 0.001). These were the result of both decrements in glucose production and increments in glucose clearance. Thus we conclude that during fasting 1) the prevention of hypoglycemia is not due solely to decreased insulin secretion. 2) Glucagon plays a primary counterregulatory role. Sympathochromaffin catecholamines are not normally critical but compensate and become critical when glucagon is deficient. Adrenomedullary epinephrine is probably the relevant catecholamine. 3) Other hormones, neurotransmitters, or substrate effects may, or may not, be involved; if they are, they appear to stand low in the hierarchy of glucoregulatory factors.

High dose epinephrine in refractory pediatric cardiac arrest.

Abstract: Cardiac arrest has a poor prognosis, regardless of age group. Children who fail to respond to two standard doses of epinephrine (0.01 mg/kg) rarely survive to hospital discharge, and most die without the return of spontaneous circulation (ROSC). We treated seven consecutive children in cardiac arrest with high dose epinephrine (0.2 mg/kg) after failure to respond to two standard doses. Six had prompt and sustained ROSC. By comparison, in the previous 20 consecutive pediatric patients with cardiac arrest in which there was no response to two standard doses of epinephrine, none had ROSC. Previous animal data as well as anecdotal human experience suggest that the standard epinephrine dose (0.01 mg/kg) may be much too low.

Lipolytic response of adipocytes to epinephrine in sedentary and exercise-trained subjects: sex-related differences.

Abstract: Adipose tissue lipolytic activity is increased in endurance-trained subjects, but little is known about the mechanisms of this increase. To understand more fully the mechanisms involved and to discover whether sex-related differences exist, biopsies of fat were performed in the periumbilical region of 20 sedentary subjects (10 women (W) and 10 men (M)) and 20 trained subjects (10 W, 10 M); the in vitro response to epinephrine of the collagenase-isolated fat cells was studied. Glycerol release, chosen as an adipocyte lipolysis indicator, was measured by bioluminescence. Dose-response curves with epinephrine (α2 and β agonist), with isoproterenol (β agonist) and epinephrine + propranolol and adenosine deaminase, were studied. Epinephrine-induced lipolysis was enhanced in trained subjects and this was due to an increased efficiency of the β-adrenergic pathway. However, differences were found between the two sexes. In trained men, the lipolysis increase resulted from the enhancement of the β-adrenergic pathway efficiency without any significant decrease in the α2-adrenergic pathway efficiency. In trained women, the lipolysis increase was not only due to the enhancement of the β-adrenergic pathway efficiency (which was greater than in trained men), but also to a significant decrease in the α2-adrenergic pathway efficiency. Despite the decrease, the α2-adrenergic pathway remained more efficient in trained women than in trained men, as was the case in sedentary subjects. It is concluded that endurance training led to better lipid mobilization and that this effect seemed greater in women than in men.

The positive inotropic effect of epinephrine on skeletal muscle: A brief review

Abstract: Chronic and acute administration of epinephrine or related sympathomimetic agents are typically prescribed for the treatment of clinical disorders such as hypotension, anaphylactic and allergic reactions, and bronchial asthma. In addition to its effects on these infirmaties and on carbohydrate metabolism, epinephrine also exerts a positive inotropic effect on fast-contracting skeletal muscle in a variety of animal species. At present, the precise mechanisms responsible for the inotropic effect are not known. This communication reviews the positive inotropic effects of epinephrine on fast-contracting skeletal muscle and discusses possible mechanisms which might mediate this phenomenon. Epinephrine potentiates muscle twitches via the second messenger, cAMP, secondary to hormone binding to membrane-bound beta-receptors. Cyclic AMP then acts to increase carbohydrate metabolism, alter sodium/potassium exchange, phosphorylate myosin isozymes, and/or alter intracellular calcium exchange. Based on theoretical grounds, the first three mechanisms can be excluded. Therefore, it is tentatively hypothesized that the effect is due to cAMP-enhanced calcium exchange within the muscle fiber and/or to increased influx of extracellular calcium. This notion is consistent with the mechanism of the positive inotropic effects of epinephrine on cardiac tissue. If this hypothesis is correct, it would also suggest a role, at least under some conditions, for extracellular calcium in the process of skeletal muscle excitation-contraction coupling.